from molecular biology to synthetic biology, what’s new? · •design team use big data and...

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From Molecular Biology to Synthetic Biology, what’s new? Sandra Taylor, Senior Research Technician, BSc (Hons), Mphil, Rsci, MIScT [email protected] (0161) 306 5131

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Page 1: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

From Molecular Biology to Synthetic Biology whatrsquos new Sandra Taylor Senior Research Technician BSc (Hons) Mphil Rsci MIScT

sandrataylormanchesteracuk (0161) 306 5131

bull 1987 - First lab job veterinary tests Bacteriology post mortems blood urine faeces tests etc

Small beginnings in Norwich after my first degree

Plant Molecular Genetics 1988 to 1998 ndash the lab grew from 6 to 16 people and several

papers were published on the way that flowering is controlled

1998 to 2001 Biochemistry Division School of Biological Sciences Manchester University ndash I supported 6 research groups sharing expertise

Topics from cell division (in toads) to asthma (in horses and people) and cultured human cells

Career Break from 2001 to 2007

bull Starting again after 6 years was a challenge but I soon got back up to speed Technical roles are very varied never boring a bit like being a Mum

2007 to present

bull I spent 7 years in the Michael Smith Building (Life Sciences) ndash various roles (cell culture cloning yeast two-hybrid)

bull In 2014 I moved to the MIB ndash more ChemistryBiochemistry focussed

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 2: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

bull 1987 - First lab job veterinary tests Bacteriology post mortems blood urine faeces tests etc

Small beginnings in Norwich after my first degree

Plant Molecular Genetics 1988 to 1998 ndash the lab grew from 6 to 16 people and several

papers were published on the way that flowering is controlled

1998 to 2001 Biochemistry Division School of Biological Sciences Manchester University ndash I supported 6 research groups sharing expertise

Topics from cell division (in toads) to asthma (in horses and people) and cultured human cells

Career Break from 2001 to 2007

bull Starting again after 6 years was a challenge but I soon got back up to speed Technical roles are very varied never boring a bit like being a Mum

2007 to present

bull I spent 7 years in the Michael Smith Building (Life Sciences) ndash various roles (cell culture cloning yeast two-hybrid)

bull In 2014 I moved to the MIB ndash more ChemistryBiochemistry focussed

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 3: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Plant Molecular Genetics 1988 to 1998 ndash the lab grew from 6 to 16 people and several

papers were published on the way that flowering is controlled

1998 to 2001 Biochemistry Division School of Biological Sciences Manchester University ndash I supported 6 research groups sharing expertise

Topics from cell division (in toads) to asthma (in horses and people) and cultured human cells

Career Break from 2001 to 2007

bull Starting again after 6 years was a challenge but I soon got back up to speed Technical roles are very varied never boring a bit like being a Mum

2007 to present

bull I spent 7 years in the Michael Smith Building (Life Sciences) ndash various roles (cell culture cloning yeast two-hybrid)

bull In 2014 I moved to the MIB ndash more ChemistryBiochemistry focussed

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 4: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

1998 to 2001 Biochemistry Division School of Biological Sciences Manchester University ndash I supported 6 research groups sharing expertise

Topics from cell division (in toads) to asthma (in horses and people) and cultured human cells

Career Break from 2001 to 2007

bull Starting again after 6 years was a challenge but I soon got back up to speed Technical roles are very varied never boring a bit like being a Mum

2007 to present

bull I spent 7 years in the Michael Smith Building (Life Sciences) ndash various roles (cell culture cloning yeast two-hybrid)

bull In 2014 I moved to the MIB ndash more ChemistryBiochemistry focussed

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 5: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Career Break from 2001 to 2007

bull Starting again after 6 years was a challenge but I soon got back up to speed Technical roles are very varied never boring a bit like being a Mum

2007 to present

bull I spent 7 years in the Michael Smith Building (Life Sciences) ndash various roles (cell culture cloning yeast two-hybrid)

bull In 2014 I moved to the MIB ndash more ChemistryBiochemistry focussed

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 6: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

2007 to present

bull I spent 7 years in the Michael Smith Building (Life Sciences) ndash various roles (cell culture cloning yeast two-hybrid)

bull In 2014 I moved to the MIB ndash more ChemistryBiochemistry focussed

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 7: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Nano-scale 3D printing

Micro-titre plates with 96 384 or even 1536 sample wells ndash technology is being developed to ldquowriterdquo strings of DNA into these tiny wells using

3D nano-printing technology

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 8: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Present Challenges Supporting SYNBIOCHEM

bull New subject(s) and equipment to learn about

bull The new SYMBIOCHEM team is 10 people and 4 robots

bull IT technology means writing electronic lab notebooks instead of paper ones

bull The new team is multidisciplinary so lots to learn but good fun

bull This is now the age of writing DNA as opposed to just reading it

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 9: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Publications (please note publications I contributed prior to 2006 were under my maiden name of Doyle)

Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARAEndofin with HD-PTP (2017) Deepankar Gahloth Colin Levy Louise Walker Lydia Wunderley A Paul Mould Sandra Taylor Philip Woodman and Lydia Tabernero Strucutre 25(7)p1011ndash1024 Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine a Nonribosomal Peptide Building Block (2015) Veronica Diez Mark Loznik Sandra Taylor Michael Winn Nicholas J W Rattray Helen Podmore Jason Micklefield Royston Goodacre Marnix H Medema Ulrike Muller Roel Bovenberg Dick B Janssen and Eriko Takano ACS Synthetic Biology - Ali N Zhang L Taylor S Mironov A Urbeacute S Woodman P (2013) Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB Curr Biol 23(6)453-61 UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting - Flavia Stefani Ling Zhang Sandra Taylor Johanna Donovan Sara Rollinson Aurelie Doyotte Kim Brownhill Janis Bennion Stuart Pickering-Brown Philip Woodman (2011) UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting Curr Biol 21(14)1245-50 - Addinall SG Mayr PS Doyle S Sheehan JK Woodman PW and Allan VJ (2001) Phosphorylation by cdc2-CyclinB1 kinase releases cytoplasmic dynein from membranes J Biol Chem 276 15939-15944 - Schultz E Carpenter R Doyle S and Coen E (2001) The gene finbriata interacts non-cell autonomously with floral regulatory genes The Plant Journal 25(5) 499-507 - McSteen PCM Vincent CA Doyle S Carpenter R and Coen ES (1999) Control of floral homeotic gene expression and organ morphogenesis in Antirhinum Development 125 2359-2369 - Ingram GC Doyle S Carpenter R Schultz EA Simon R and Coen ES (1997) Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirhinum EMBO J 16 6521-6534 - Carpenter R Copsey L Vincent C Doyle S Magrath R and Coen E (1995) Control of flower development and phyllotaxy by meristem identity genes in Antirhinum The Plant Cell 7 2001-2011 - Simon R Carpenter R Doyle S and Coen ES (1994) Fimbriata controls flower development by mediating between mertistem and organ identity genes Cell 78 99-107 - Hudson A Carpenter R Doyle S and Coen ES (1993) Olive a key gene required for chlorophyll biosynthesis in Antirhinum majus EMBO J 12 3711-3719 - Luo D Coen ES Doyle S and Carpenter R (1991) Pigmentation mutants produced by transposon mutagenesis in Antirhinum majus Plant J 1 59-69 - Coen ES Romero JM Doyle S Elliott R Murphy G and Carpenter R (1990) Floricaula a homoetic gene required for flower development in Antirhinum majus Cell 63 1311-1322 Published Abstract Davies L Gkourtza A Symeou C Lynch J Taylor S Demonacos C and M Krstic-Demonacos (2009) Endocrine Abstracts 19 Society for Endocrinology BES 2009 -

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 10: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Six Synthetic Biology Centres across the UK

bull Centre for Synthetic Biology and Innovation in London

bull Synthetic Biology Research Centre in Nottingham

bull BrisSynBio in Bristol

bull The UK Centre for Mammalian Synthetic Biology in Edinburgh

bull Warwick Integrative Synthetic Biology Centre

bull SYNBIOCHEM in Manchester (speciality and fine chemicals)

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 11: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

DESIGN-BUILD-TEST (What is SYNBIOCHEM)

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 12: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Current research themes

bull Terpenoids

bull Alkaloids

bull Flavanoids

bull Technologyplatform development

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 13: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Our semi-automated laboratory

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 14: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

SYNBIOCHEMndasha SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals Pablo Carbonell Andrew Currin Mark Dunstan Donal Fellows Adrian Jervis Nicholas JW Rattray Christopher J Robinson Neil Swainston Maria Vinaixa Alan Williams Cunyu Yan Perdita Barran Rainer Breitling George Guo-Qiang Chen Jean-Loup Faulon Carole Goble Royston Goodacre Douglas B Kell Rosalind Le Feuvre Jason Micklefield Nigel S Scrutton Philip Shapira Eriko Takano Nicholas J Turner Biochemical Society Transactions Jun 09 201644(3)675-677DOI 101042BST20160009 ldquoThe Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals The Centres integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals productionrdquo

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 15: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Scientometrics September 2017 Volume 112 Issue 3 pp 1439ndash1469

ldquoTracking the emergence of synthetic biologyrdquo Philip Shapira Seokbeom Kwon Jan Youtie

ldquoSynthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research innovation and policy interest in recent yearsrdquo

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 16: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Fragrances and flavours

Natural fragrances and flavours are used in many forms and are found in many types of foods and beverages These can be produced naturally but sometimes there is more demand than can be supplied We will look at a range of natural ldquosmellsrdquo and ask how these can be used and whether there are any substitutes Part of our research is to look at novel ways to make in-demand fragrances

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 17: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

The search for novel materials

bull Materials (Basel) 2016 Jul 119(7) pii E560 doi 103390ma9070560

bull Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

bull Hardy JG1 Torres-Rendon JG2 Leal-Egantildea A3 Walther A4 Schlaad H5 Coumllfen H6 Scheibel TR7 bull Author information bull Abstract bull Materials based on biodegradable polyesters such as poly(butylene terephthalate) (PBT) or

poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT) have potential application as pro-regenerative scaffolds for bone tissue engineering Herein the preparation of films composed of PBT or PBTAT and an engineered spider silk protein (eADF4(C16)) that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering

bull KEYWORDS bull biodegradable polymers biomaterials biomineralization bone tissue engineering recombinant

protein spider silk bull PMID 28773681 PMCID PMC5456849 DOI 103390ma9070560

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 18: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Menthol

Minty flavour cool sensation

Mentha avensis and mentha piperita

Used for over 2000 years in some parts of the world

Earliest reference in the West in 1771

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 19: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Novel ways to produce rare or novel compounds

bull Select a host organism to express the chosen enzyme pathway ndash Escherichia coli yeast etc

bull Design team use Big Data and algorithms to select good candidate pathways ndash varying elements like varying strength promoters ribosomal binding sites heterologous enzymes with useful function etc

bull Build team use automation to assemble and then express as many permutations as possible

bull Test team analyse the expressed compounds to identify what amount of target chemical was synthesised

bull Design team analyse results and re-run algorithms to come up with better designs which are then made and tested

bull Finally strain and media optimisation to maximise yields

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 20: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Advantages

bull Relatively cheap feed stocks (eg glucose and glycerol) bull Using relatively simple host organisms well

characterised defined media and growth conditions bull Able to test many permutations of pathways quickly to

optimise production bull Some chemical processes are expensive or difficult but

biological enzymes could do the same job bull Agriculture is crop dependent (time of year) and

weather dependent and for example vanilla is in higher demand than can be produced naturally

bull Biological enzyme promiscuity (substitution)

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 21: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Disadvantages

bull Co-factors and supplements may be expensive

bull Biological enzyme promiscuity

bull Metabolic pathways complex

bull May impact traditional agriculture

bull Chemical methods tried and tested

bull

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 22: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Automation and the Technician

bull As Robots and Artificial Intelligence are found increasingly frequently in Industry and the workplace how will this change the technical role

bull Advantages for large scale and repetitive tasks eg 96 format sequening PCR DNA assembly etc

bull Not so good for fine tuning protocol optimisation biological variation (eg colony picking)

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 23: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Acknowlegements bull Nick Weisse (Public outreach)

bull Helen Toogood (Design an enzyme)

bull Rob Meckin

bull Barbara Ribeiro

bull SYNBIOCHEM Directors Prof Nigel Scrutton Prof Eriko Takano and Prof Nick Turner

bull Director of Operations Dr Ros Le Feuvre

bull And my team

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung

Page 24: From Molecular Biology to Synthetic Biology, what’s new? · •Design team use Big Data and algorithms to select good candidate pathways – varying elements like varying strength

Neil Swainston

Alan Williams

Maria Vinaixa

Andy Currin

Mark Dunstan

Adrian Jervis

Donal Fellows

Ros Le Feuvre

Cunyu Yan Nik Rattray

Kat Holloywood

Reynard Speiss Rehana Sung