Achievements 2010 to 2014 The ACRF Centre for KinomicsTM

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Contents

Snapshot ....................................................................................................................................................... 1

The Story So Far ............................................................................................................................................ 2

ACRF-CFK Directors and Management ......................................................................................................... 4

ACRF-CFK Affiliated Researchers .................................................................................................................. 4

ACRF-CFK Research Advisory Committee ..................................................................................................... 4

Funding Awarded to Projects Utilising ACRF-CFK ......................................................................................... 5

Research Achievements: Publications .......................................................................................................... 5

Research Achievements: Presentations ........................................................................................................ 9

Services to Research: Symposia hosted by ACRF-CFK ................................................................................ 16

Services to Research: Selected Workshops & Seminar Series hosted by ACRF-CFK................................... 18

Appendix A: Media Coverage and Photographs ......................................................................................... 19

Snapshot

The Australian Cancer Research Foundation Centre for Kinomics (ACRF CFK) – a joint venture between Children’s Medical Research Institute (CMRI) and the University of Newcastle (UoN) — is an Australian-first that will provide an entirely new approach to the understanding of therapeutic drugs and ways to improve them.

The ACRF-CFK brings the new discipline of Kinomics to Australia and a completely novel drug design strategy. It will enable better understanding of current therapies and their unwanted side effects, as well as the development of new drugs for a multitude of human diseases, many of which are currently without any suitable treatment.

This significant, non-commercial initiative builds upon demonstrated research excellence, leadership and successful collaborations between scientists from CMRI and UoN. ACRF CFK is equipped with state-of-the-art instrumentation and expert personnel, thanks to generous funding from the Ramaciotti Foundations and the Australian Cancer Research Foundation (ACRF), who provided grants of $1 million and $3.1 million respectively. ACRF CFK is named in honour of the Australian Cancer Research Foundation.

“This facility offers hope to patients and families living with diseases where there is neither cure nor effective treatment. The research conducted has the potential to improve the future health of Australians

and people around the world.” - The Hon. Tanya Plibersek MP.

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The Story So Far

2009 Professors Robinson and McCluskey are awarded The Ramaciotti Foundations Biomedical Research

Award. This $1 million grant is an indication of the level of support for this cutting-edge facility from the Australian medical research establishment.

Image (L-R): Professor Adam McCluskey (University of Newcastle, Australia), Professor Frank Martin (President, CMRI Board of

Directors), Mrs Carolyn Forster (Vice President, CMRI Board of Directors), Professor Roger Reddel (Lorimer Dods Professor and

Director, CMRI), Professor Phillip J Robinson (Head of Cell Signalling Unit, CMRI).

2009 The Australian Cancer Research Foundation (ACRF)

announces that $3.1 million is to be awarded to CMRI and The University of Newcastle, Australia for

the facility, which is officially named the ACRF Centre for Kinomics (ACRF CFK) in recognition of the

Foundation’s generous support.

Image (L-R): One of several mass-spectrometers purchased with the ACRF grant.

2009 The Ian Potter Foundation award a $100,000 seed

grant to Professor Phil Robinson (CMRI) and Professor Adam McCluskey (University of Newcastle,

Australia) to help initiate a major expansion of current mass spectrometry technology into a

national facility, furthering research into cancer and brain function.

Image: A mass spectrometer purchased with the Ian Potter Foundation contribution.

2009 Cancer Institute NSW awards Professor Robinson

with a $979,371 major equipment grant to complete the setup of ACRF CFK. AB SCIEX is the

supplier of the mass spectrometry equipment.

Image (L-R): ACRF CFK in its former facility room at Children’s Medical Research Institute.

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2 February 2012 CMRI is visited by the former Governor General of Australia, The Honourable Dame Quentin Bryce AD

CVO, who stopped by to view the soon-to-be-opened ACRF CFK.

Image (L-R): The Honourable Dame Quentin Bryce AD CVO, Professor Phil Robinson, Dr Valentina Valova, Dr Annie Quan

27 September 2012 ACRF CFK is officially launched at CMRI. Dignitaries,

researchers, major supporters and special guests celebrate this new, world-class facility.

Image (L-R): Tom Dery (Chairman, ACRF), Professor Adam McCluskey (University of Newcastle), Dr Valentina Valova

(Manager, Biomedical Proteomics and ACRF CFK), Professor Phil Robinson (CMRI), Professor Roger Reddel, Ed Husic MP.

20 June 2013 The 1st Chemical Proteomics Symposium is hosted

by ACRF CFK at CMRI. This is the first scientific event in Australia dedicated to chemical proteomics

and its application to developing new and more effective treatments.

Image: Symposium presenters and guests.

October 2014 Following the opening of CMRI’s new building in

August 2014, ACRF CFK moves into its new, custom-built facility. This highly specialised space houses the mass spectrometers under pristine conditions.

It is expected that usage of ACRF CFK will increase as research programs across Australia look to

proteomics and kinomics to give new insights into disease and develop new and more effective

treatments.

Image: ACRF CFK, now located on Level 6 at CMRI.

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ACRF-CFK Directors and Management

Phillip J Robinson BSc (Hons) PhD Director, ACRF Centre for Kinomics Head, Cell Signalling Unit, Children’s Medical Research Institute NHMRC Senior Principal Research Fellow Professor, Faculty of Medicine, University of Sydney Professor of Chemistry, The University of Newcastle, Australia Adam McCluskey BSc (Hons) PhD Director, ACRF Centre for Kinomics Professor of Chemistry & Director, Centre for Chemical Biology (The University of Newcastle, Australia) Honorary Scientist, Children’s Medical Research Institute Valentina A Valova BSc/Eng (Biotech) MSc (Biotech) MAppSc (Biopharm) Manager, Biomedical Proteomics & ACRF Centre For Kinomics

ACRF-CFK Affiliated Researchers

Mark Graham BSc (Hons) PhD Protein Biochemistry Group Leader, Children’s Medical Research Institute Peter Hains BSc (Hons) PhD Senior Research Officer, Cell Cycle Unit, Children’s Medical Research Institute Kasper Engholm-Keller BSc MSc PhD Visiting Postdoctoral Fellow, University of Southern Denmark

ACRF-CFK Research Advisory Committee

Mr Michael Crouch Director, Discovery Program for TGR BioSciences, Adelaide Associate Professor Martin R. Larsen Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark Professor Ron Quinn Director, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Australia

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Funding Awarded to Projects Utilising ACRF-CFK

NHMRC Project Grant (P. Robinson). Role of Dynamin Isoforms in Modes of Synaptic Endocytosis. 2011-2013. NHMRC Project Grant (P. Robinson & A. McCluskey). Sulfonadyn-based Dynamin I-Specific Inhibitors and Epilepsy. 2011 – 2013. NHMRC Development Grant (A. McCluskey, P. Robinson, T. O’Brien, M. Chircop, J. Sakoff). Development Pthaladyn-based Dynamin I-Selective Inhibitors for Treatment of Epilepsy. 2011- 2013. NHMRC Project Grant (P. Robinson & A. McCluskey). Mechanism of Dynamin Ring Stabilizer Compounds Controlling the Actin Cytoskeleton. 2012-2014. NHMRC Project Grant (M. Chircop, P. Robinson, A. McCluskey & J. Sakoff). The Role of Clathrin in the Spindle Assembly Checkpoint and as a Target of Anti-Cancer Therapy. 2012-2014. Cancer Institute NSW (P. Robinson). Multi-Centre Screening and Development Platform for pre-clinical drugs for glioblastoma. 2013-2014. NHMRC Project Grant (P. Robinson & M. Graham). Phosphorylation of synaptic vesicle glycoprotein 2 (SV2) regulates. 2013-2015. NHMRC Research Fellowship (P. Robinson). Molecular mechanisms and pharmacology of the dynamins. 2013-2017. NHMRC Project Grant (P. Robinson). Molecular mechanisms of dynamin-mediated endocytosis in nerve terminals. 2014-2017. NHMRC Project Grant (P. Robinson & M. Graham). Phosphorylation of synaptic vesicle glycoprotein 2 (SV2) regulates. 2013-2015.

Research Achievements: Publications

2010

Baker, M., Smith, N. D., Hetherington, L., Taubman, K., Graham, M. E., Robinson, P.J., Aitken, R. J. (2010) Label-free Quantitation of Phosphopeptide Changes During Rat Sperm Capacitation. Journal of Proteome Research. 9, 718-729. Full Article: Available at http://pubs.acs.org/doi/abs/10.1021/pr900513d Impact Factor: 5.46 Cited: 13 Featured: Research Profile within J. Proteome Res.: by Laura Cassiday (2010) Phosphoprotein changes during sperm capacitation. p639. DOI: 10.1021/pr9011552

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Chan, L. S., Hansra, G., Robinson, P. J., Graham, M. E. (2010) Differential phosphorylation of dynamin I isoforms in subcellular compartments demonstrates the hidden complexity of phosphoproteomes. Journal of Proteome Research. 9, 4028-37. Full Article: Available at http://pubs.acs.org/doi/abs/10.1021/pr100223n Impact Factor: 5.46 Cited: 10

Howes, M. T., Kirkman, M., Riches, J., Cortese, K., Walser, P. J., Simpson, F., Hill, M. M., Jones, A., Lundmark, R., Lindsay, M. R., Hernandez-Deviez, D. J., Hadzic, G., McCluskey, A., Bashir, R., Liu, L., Pilch, P., McMahon, H., Robinson, P. J, Hancock, J. F., Mayor, S., Parton, R. G. (2010) Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. Journal of Cell Biology. 190, 675-691. Full Article: http://jcb.rupress.org/content/190/4/675.long

2011

Chircop, M., Sarcevic, B., Larsen, M. R., Malladi, C. S., Chau, N., Zavortink, M., Smith, C. M., Quan, A., Anggono, V., Hains, P. G., Graham, M. E., Robinson, P. J. (2011) Phosphorylation of dynamin II at serine-764 is associated with cytokinesis. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1813, 1689-99. Full Article: Available at http://www.sciencedirect.com/science/article/pii/S0167488910003356 Impact Factor: 4.73 Cited: 9

Graham, M. E., Thaysen-Andersen, M., Bache, N., Craft, G. E., Larsen, M. R., Packer, N. H., Robinson, P. J. (2011) A Novel Post-translational Modification in Nerve Terminals: O-Linked N-Acetylglucosamine Phosphorylation. Journal of Proteome Research. 10, 2725-33. Full Article: http://pubs.acs.org/doi/abs/10.1021/pr1011153 Featured: Research Highlights: Post-translational modifications: A phosphate pile-up. Nature Chemical Biology 7, 407 (2011). doi:10.1038/nchembio.606 - http://goo.gl/1qWsiU Featured: Faculty of 1000 featured article http://f1000.com/prime/11682958 (places this in the top 2% of published articles in biology and medicine).

Kozlov, S. V., Graham, M. E., Jakob, B., Tobias, F., Kijas, A. W., Tanuji, M., Chen, P. Robinson, P. J., Taucher-Scholz, G., Suzuki, K., So, S., Chen, D., Lavin, M. F. (2011) Autophosphorylation and ATM activation: Additional sites add to the complexity. The Journal of Biological Chemistry. 286, 9107-19. Full Article: http://www.jbc.org/content/286/11/9107.long Impact Factor: 5.33 Cited: 26

Tarleton, M., McCluskey, A. (2011) A flow chemistry route to 2-phenyl-3-(1H-pyrrol-2-yl)propan-1-amines. Tetrahedron Letters. 52, 1583-1586. Full Article: http://www.sciencedirect.com/science/article/pii/S0040403911001365

Xue, J., Graham, M. E., Novelle, A. E., Sue, N., Gray, N., McNiven, M. A., Smillie KJ, Cousin, M. A., Robinson, P. J. (2011) Calcineurin Selectively Docks With The Dynamin Ixb Splice Variant To Regulate Activity-Dependent Bulk Endocytosis. Journal of Biological Chemistry. 286, 30295-303.

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Full Article: http://www.jbc.org/content/286/35/30295.long Impact Factor: 5.33 Cited: 10

2012

Bolderson, E., Savage, K. I., Mahen, R., Pisupati, V., Graham, M. E., Richard, D. J., Robinson, P. J., Venkitaraman, A. R., Khanna, K. K. (2012) Kruppel-associated Box (KRAB)-associated Co-repressor (KAP-1) Ser-473 Phosphorylation Regulates Heterochromatin Protein 1β (HP1-β) Mobilization and DNA Repair in Heterochromatin. Journal of Biological Chemistry. 287, 28122-31. Full Article: http://www.jbc.org/content/287/33/28122.long Impact Factor: 5.33 Cited: 5

Graham, M. E., Stone, R. S., Robinson, P. J., Payne, R. J. (2012) Synthesis and Protein Binding Studies of a Peptide Fragment of Clathrin Assembly Protein AP180 Bearing an O-Linked β-N-Acetylglucosaminyl-6-phosphate Modification. Organic & Biomolecular Chemistry. 10, 2545-51. Full Article: http://pubs.rsc.org/en/Content/ArticleLanding/2012/OB/c2ob07139h#!divAbstract IF 3.45 Cited: 0

Palmisano, G., Parker, B. L, Engholm-Keller, K., Lendal, S. E., Kulej, K., Schulz, M., Schwämmle, V., Graham, M. E., Saxtorph, H., Cordwell, S. J., Larsen, M. R. (2012) A novel method for the simultaneous enrichment, identification and quantification of phosphopeptides and sialylated glycopeptides applied to a temporal profile of mouse brain development. Molecular & Cellular Proteomics. 11, 1191-1202. Full Article: http://www.mcponline.org/content/11/11/1191.long Impact Factor: 8.35 Cited: 13

Quan, A., Xue, J., Wielens, J., Smillie, K., Anggono, V., Parker, M. W. Cousin, M. A., Graham, M. E., Robinson, P. J. (2012) Phosphorylation of syndapin I F-BAR domain at two helix capping motifs regulates membrane tubulation. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 109, 3760-5. Full Article: http://www.pnas.org/content/109/10/3760.long IF 9.77 Cited: 10

2013

Engholm-Keller, K., Larsen, M.R. (2013) Technologies and challenges in large-scale phosphoproteomics. Proteomics. 13: 910-31. Full Article: http://onlinelibrary.wiley.com/doi/10.1002/pmic.201200484/abstract Impact Factor: 4.223

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Gordon, C.P., Venn-Brown, B., Robertson, M.J., Young, K.A., Chau, N., Quan, A., Robinson, P.J., McCluskey, A. (2013) Development of second generation indole based dynamin GTPase inhibitors. Journal of Medicinal Chemistry. 56, 46-59. Full Article: http://pubs.acs.org/doi/abs/10.1021/jm300844m

McCluskey, A., Daniel, J. A., Hadzic, G., Chau, N., Clayton, E. L., Mariana, A., Whiting, A., Lloyd, J., Quan, A., Moshkanbaryans, L., Perera, S., Chircop, M., McGeachie, A. B., Howes, M. T., Parton, R. G., Campbell, M., Sakoff, J. A., Wang, X., Sun, J.Y., Robertson, M. J., Deane, F. M., Nguyen, T. H., Meunier, F. A., Cousin, M. A., Robinson, P. J. (2013) Building a better dynasore: The dyngos potently inhibit dynamin and endocytosis. Traffic. 14, 1272-1289. Full Article: http://onlinelibrary.wiley.com/doi/10.1111/tra.12119/abstract

McGeachie, A. B., Odell, L. R., Quan, A., Chau, N., Hill, T.A., Keating, D.J., Cousin, M. A., van Dam, E. M., Daniel, J., Mariana, A., Whiting, A., Perera, S., Novelle, A., Gilbert, J., Sakoff, J., Chircop, M., McCluskey, A., Robinson, P. J. (2013) The Pyrimidyns: Novel small molecule PH domain targeted pyrimidine-based dynamin inhibitors. ACS Chemical Biology. 8, 1507-1518. Full Article: http://pubs.acs.org/doi/abs/10.1021/cb400137p

Parker, B. L., Thaysen-Andersen, M., Solis, N., Scott, N. E., Larsen, M. R., Graham, M. E., Packer, N. H., Cordwell, S. J. (2013) Site-specific glycan-peptide analysis for determination of N-glycoproteome heterogeneity. Journal of Proteome Research. 12, 5791-800. Full Article: http://pubs.acs.org/doi/abs/10.1021/pr400783j IF: 5.46 Cited: 3

Quan A., Robinson P.J. (2013) Syndapin, a membrane remodelling and endocytic F-BAR protein. The FEBS Journal. 280: 5198-212. Full Article: http://onlinelibrary.wiley.com/doi/10.1111/febs.12343/pdf

2014

Chan, LS., Moshkanbaryans, L., Xue, J., Graham, M. E. (2014) The ∼16 kDa C-Terminal Sequence of Clathrin Assembly Protein AP180 Is Essential for Efficient Clathrin Binding. PLoS One. 9, e110557. Full Article: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0110557

Dyson, L., Wright, A.D., Young K.A, Sakoff, J.A., McCluskey, A. (2014) Synthesis and anticancer activity of focused compound libraries from the natural product lead, oroidin. Bioorganic and Medicinal Chemistry. 22, 1690-1699. Full Article: http://www.sciencedirect.com/science/article/pii/S0968089614000492

Gordon, C. P., Hizartzidis, L., Tarleton, M., Sakoff, J. A., Gilbert, J., Campbell, B., Gasser, R. B., McCluskey, A. (2014) Discovery of acrylonitrile based small molecules active against Haemonchus contortus. Medicinal Chemistry Communications. 2014. 5, 159-164. Abstract: http://pubs.rsc.org/en/content/articlelanding/md/2014/c3md00255a#!divAbstract

Hizartzidis, L., Cossar, P. J., Robertson, M. J., Simone, M. I., Young, K. A., McCluskey, A., Gordon, C. P. (2014) Expanding the Utility of Flow Hydrogenation – A Robust Protocol Restricting Hydrodehalogenation. RSC Advances. 4, 56743-56748.

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Abstract: http://pubs.rsc.org/en/content/articlelanding/ra/2014/c4ra09605c#!divAbstract

Hizartzidis, L., Tarleton, M., Gordon, C.P., McCluskey, A. (2014) Chemoselective flow hydrogenation approaches to isoindole-7-carboxylic acids and 7-oxa-bicyclio[2.2.1]heptanes. RSC Advances. 4, 9709-9722. Abstract: http://pubs.rsc.org/en/content/articlelanding/2013/ra/c3ra47657j#!divAbstract

MacGregor, K. A., Abdel-Hamid, M. K., Odell, L. R., Chau, N., Mariana, A., Robinson, P. J., McCluskey, A. (2014) Development of quinone-based analogues as a new class of dynamin GTPase inhibitors. European Journal of Medicinal Chemistry. 85, 191-206. Full Article: http://www.pubfacts.com/fulltext_frame.php?PMID=25084145&title=Development%20of%20quinone%20analogues%20as%20dynamin%20GTPase%20inhibitors.

MacGregor, K. A., Robertson, M. J., Young, K. A., von Kleist, L., Stahlschmidt, W., Whiting, A., Chau, N., Robinson, P. J., Haucke, V., McCluskey, A. (2014) Development of 1,8-naphthalimides as clathrin inhibitors. Journal of Medicinal Chemistry. 57, 131-143. Full Article: http://pubs.acs.org/doi/abs/10.1021/jm4015263

Moshkanbaryans, L., Chan, L-. S., Graham, M. E. (2014) The Biochemical Properties and Functions of CALM and AP180 in Clathrin Mediated Endocytosis. Membranes. 4, 388-413. Full Article: http://www.mdpi.com/2077-0375/4/3/388

Robertson, M. J., Deane, F. M., Robinson, P. J., Haucke, V., McCluskey, A. (2014) Synthesis of the Pitstop family of clathrin inhibitors. Nature Protocols. 9, 1592-1606. Full Article: http://www.nature.com/nprot/journal/v9/n7/full/nprot.2014.106.html

Robertson, M. J., Deane, F. M., Robinson, P. J., McCluskey, A. (2014) Synthesis of a dynamin GTPases modulators toolkit: Dynole 34-2, Dynole-2-24 and Dyngo 4a. Nature Protocols. 9, 851-870. Full Article: http://www.nature.com/nprot/journal/v9/n4/full/nprot.2014.046.html

Stahlschmidt, W., Robertson, M.J., Chau, N., Robinson, P.J., McCluskey, A., Haucke, V. (2014) Clathrin terminal domain-ligand interactions regulate sorting of mannose 6-phosphate receptors mediated by AP-1 and GGA adaptors. The Journal of Biological Chemistry. 289, 4906-4918. Full Article: http://www.jbc.org/content/289/8/4906.long

Trinh, T. N., Hizartzidis, L., Lin, A. Y. S., McCluskey, A., Gordon, C. P. (2014) An efficient continuous flow approach to furnish furan-based biaryls. Organic and Biomolecular Chemistry. DOI: 10.1039/c4ob0164f. Abstract: http://pubs.rsc.org/en/Content/ArticleLanding/2014/OB/C4OB01641F#!divAbstract

Research Achievements: Presentations

Plenary Speakers

McCluskey, A. (2010) From Dyngos to Dynasore and beyond. The 'Dyns', dynamin inhibitors as novel therapeutic agents. ASCEPT Keynote Lecture, AHMR Congress (Melbourne, VIC, Australia).

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Robinson, P.J. (2012) Biological Psychiatry Australia 2nd Annual Scientific Meeting (Melbourne, VIC, Australia).

Robinson, P.J. (2012) 6th Garvan Signalling Symposium (Sydney, NSW, Australia).

Robinson, P.J. (2012) ISN-Wiley-Blackwell-JNC-International Lecture, Annual Meeting of Indian Academy of Neurosciences (Guru Nanak Dev University Amritsar, India).

McCluskey, A. (2013) Rings, helices, macromolecular structures and the inhibition of dynamin GTPase as a novel therapeutic target. RACI - Biomolecular in the Bush Conference (Leura, VIC, Australia).

McCluskey, A. (2013) A chemical proteomics toolkit to streamline drug development. 1st Chemical Proteomics Symposium. Children’s Medical Research Institute (Sydney, NSW, Australia).

Invited Speakers

Chircop, M. (2011) Dynamin inhibitors are a new class of anti-mitotic agents with anti-cancer properties. Hunter Medical Research Institute (Newcastle, NSW, Australia).

Robinson, K., McCluskey, A., Attalla, M.I. (2012) The Effect Molecular Structural Variations has on the CO2 Absorption Characteristics of Heterocyclic Diamines for Amine-based Post Combustion CO2 Capture. GHGT-11 Conference: International conference on Greenhouse Gas Technologies (Kyoto, Japan).

Robinson, P.J. (2012) Melbourne Protein Group, 2nd MPG Postdoctoral Symposium (Melbourne, VIC, Australia).

Robinson, P.J. (2012) The 12th Hunter Meeting, (Hunter Valley, NSW, Australia).

Robinson, P.J. (2012) Exocytosis and Endocytosis of the USA Biophysical Society (San Diego, CA, USA).

Robinson P.J. (2012) Department of Pharmacology, University of Melbourne (Melbourne, VIC, Australia).

Robinson, P.J. (2012) BABS Seminar, School of Biotechnology and Biomolecular Sciences, University of New South Wales (Sydney, NSW, Australia).

Robinson, P.J. (2012) Dynamin Phosphorylation and Dynamin Modulators in Synaptic Endocytosis. Biophysics Seminar, Department of Pharmacology, School of Medicine, University of Washington (Seattle, WA, USA).

Valova V.A. (2012) Plan for the Future (featuring The ACRF CFK). 1ST Kinomics Retreat, 19- 21 March 2012.

Abdel-Hamid, M.K., Robinson, P.J., McCluskey, A. (2013) Dynamin I GTPase Inhibitors: New Discovery using de Novo Structure-Based Molecular Design. Brisbane Biological and Organic Chemistry Symposium (Brisbane, QLD, Australia).

Graham, M.E. (2013) Chemical proteomics approach for determining a glycosylphosphorylation-regulated protein function. 1st Chemical Proteomics Symposium, Children’s Medical Research Institute (Sydney, NSW, Australia).

McCluskey, A. (2013) Small molecule Ryngo compounds alter dynamin conformation and stimulate GTPase activity. International Symposium on Advancing the Chemical Sciences:

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Challenges in Chemical Biology (ISACS-11), Massachusetts Institute of Technology (Boston, MA, USA).

Valova, V.A. (2013) Seriously Wanting All The Hits (featuring The ACRF Centre for Kinomics). Lorne Proteomics User Meeting (Lorne, VIC, Australia).

Valova, V.A., Robinson, P.J. (2013) Mass Spectrometry Approaches for Signalling Pathways (featuring The ACRF CFK). Westmead Hospital Seminar Series (Sydney, NSW, Australia).

McCluskey, A. (2013). A chemical proteomics toolkit to streamline drug development . 1st Chemical Proteomics Symposium, Children’s Medical Research Institute (Sydney, NSW, Australia).

Selected Presentations

Engholm-Keller, K. (2012) Proteomics and Beyond. Macquarie University (Sydney, Australia).

Engholm-Keller, K. (2012) 6th Garvan Signalling Symposium (Sydney, Australia)

Graham, M.E. (2012) The regulatory phosphoproteome of synaptic vesicle endocytosis. 17th Lorne Proteomics Symposium (Lorne, VIC, Australia)

Engholm-Keller K., (2013) Quantitative proteomics and phosphoproteomics for identification of novel regulatory mechanisms of lipid and energy metabolism in C. elegans. Lorne Proteomics Symposium (Lorne, VIC, Australia)

Graham, M.E., (2013) An optimised workflow for defining the molecular interactions of clathrin assembly proteins. 18th Lorne Proteomics Symposium (Lorne, VIC, Australia).

Oral Presentations

Bache, N., Larsen, M.R., Robinson, P.J., Graham, M.E. (2010) Mechanisms of synaptic vesicle endocytosis revealed by its regulatory phosphoproteome. 6th International Barbados Proteomics Conference HUPO Workshop on Organellar Proteomics, The Human Proteome Project and Disease, Bellairs Research Institute (Holetown, Barbados).

Graham M.E., Bache, N., Larsen, M.R., Robinson, P.J. (2010) Characterisation of a new post-translational modification: O-GlcNAc-phosphate. HUPO2010 (Sydney, NSW, Australia).

Quan, A. (2011) Phosphorylation of Syndapin I F-BAR domain regulates membrane tubulation. Symposium 41 - Signalling at the Level of Tissue and Organs, ComBio2011, Cairns Convention Centre (Cairns, QLD, Australia).

Quan, A. (2011) Phosphorylation of Syndapin I F-BAR domain regulates membrane tubulation. Oral-Session 1 – Synaptic Transmission, 31st Annual Australian Neuroscience Society (ANS) Meeting (Auckland, New Zealand).

Bache, N., Rao, S., Honeyman, N., Larsen, M.R., Robinson, P.J., Graham, M.E. (2012) The regulatory phosphoproteome of synaptic vesicle endocytosis. 17th Lorne Proteomics Symposium (Lorne, VIC, Australia).

Miller, L. (2012) Lysosomes and Endocytosis. Gordon Conference (New Hampshire, USA)

Chan, L., Janakan, V., Graham, M.E. (2013) An optimized workflow for defining the molecular interactions of clathrin assembly proteins. 18th Lorne Proteomics Symposium (Lorne, VIC, Australia).

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Miller, L. (2013) Isolating the Bulk Endosome from Nerve Terminals. Australian Neuroscience Society (Melbourne, VIC, Australia)

Engholm-Keller, K., Robinson, P.J, Graham, M.E. (2014) Investigation of the widespread phosphorylation signalling associated with presynaptic plasticity. Inter-University Neuroscience and Mental Health Conference, The University of Sydney (Sydney, NSW, Australia).

Seminar Presentations

McCluskey, A. (2010) A chemical biology capability. Chemistry - University of Newcastle, Australia (Newcastle, NSW, Australia).

McCluskey, A. (2011) The ACRF Centre for Kinomics. University of Newcastle, Australia (Newcastle, NSW, Australia).

Chan, L. (2013) The Role of AP180 Primary Structure in Synaptic Vesicle Endocytosis. CMRI Seminar Series (Sydney, NSW, Australia).

Engholm-Keller, K. (2013) Does phosphate improve memory? Phosphorylation-dependent modulation of phosphatase activity via phosphatase regulators in synaptic plasticity. CMRI Seminar Series (Sydney, NSW, Australia).

Mariana, A. (2013) The Development of Isoform-Selective Dynamin Modulators. CMRI seminar series (Sydney, NSW, Australia).

McCluskey, A. (2013) Slugs, Bugs and Drugs. Children’s Medical Research Institute (Sydney, NSW, Australia).

McCluskey, A. (2013) Slugs, Bugs and Drugs. Biology - University of Newcastle, Australia (Newcastle, NSW, Australia).

McCluskey, A. (2013) Small molecules and dynamin GTPase as a novel glioblastoma, anti-epilepsy and kidney disease drug target. Institute for Molecular Biosciences, The University of Queensland (Brisbane, QLD, Australia).

Miller, L. (2013) Synaptic vesicles: Where do they come from? CMRI Seminar Series (Sydney, NSW, Australia).

Quan, A. (2013) The Role of Syndapin I Phosphorylation in Neurons. CMRI Seminar Series (Sydney, NSW, Australia).

Xue, J. (2013) Dynamin – a tale of two tails. CMRI Seminar Series (Sydney, NSW, Australia).

Robertson, M.J., McCluskey, A. (2014) Application of flow chemistry to medicinal chemistry. James Cook University (Townsville, QLD, Australia).

Poster Presentations

Bache, N., Larsen, M.R., Robinson, P.J., Graham, M.E. (2010) Mechanisms of synaptic vesicle endocytosis revealed by its regulatory phosphoproteome. HUPO2010 (Sydney, NSW, Australia).

Chan, L., Robinson, P.J, Graham, M.E. (2010) AP180 binding to clathrin in endocytosis: new insight. OzBio2010 (Melbourne, VIC, Australia).

Chan, L., Robinson, P.J, Graham, M.E. (2010) Hidden Complexities of Phosphoproteomics Revealed by Targeted Analysis of Dynamin I Isoforms. HUPO2010 (Sydney, Australia).

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Stehn, J., Schevzov, G., Bonello, T., McCluskey, A., Haass, N., Palmer, S., Hardeman, E., Allanson, M., Reeve, V., Gunning, P. (2010) Tropomyosin Tm5NM1: A novel target for cancer therapy. 7th Annual International Melanoma Congress (Sydney, NSW, Australia).

Stehn, J., Schevzov, G., Bonello, T., McCluskey, A., Haass, N., Palmer, S., Hardeman, E., Allanson, M., Reeve, V., Gunning, P. (2010) Tropomyosin Tm5NM1: A novel target for cancer therapy. 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (Berlin, Germany).

Turner, N.W., Bowyer, M.C., McCluskey, A., Holdsworth, C.I. (2010) Fluorescent Molecularly Imprinted Polymer for the Detection of 2,4-Dinitrotoluene. MIP2010 – The Future of Molecular Imprinting, Sixth International Meeting on Molecular Imprinting (New Orleans, LA, USA).

Turner, N., Holdsworth, C.I., Donne, S., McCluskey, A.,Bowyer, M.C. (2010) Microwave induced MIP synthesis: comparative analysis of thermal and microwave induced polymerisation of caffeine imprinted polymers. MIP2010 – The Future of Molecular Imprinting, Sixth International Meeting on Molecular Imprinting (New Orleans, LA, USA).

Wright, K., Bowyer, M. C., McCluskey, A., Holdsworth, C. I. (2010) A Comparison Between The Non-Covalent and Semi-covalent Benzylpiperazine MIPs. MIP2010 – The Future of Molecular Imprinting, Sixth International Meeting on Molecular Imprinting (New Orleans, LA, USA).

Zayas, H. A., Holdsworth, C. I., Bowyer, M. C., McCluskey, A. (2010) Molecularly Imprinted Polymers for Phosphotyrosine Using Biphenyl Monomers. MIP2010 – The Future of Molecular Imprinting, Sixth International Meeting on Molecular Imprinting (New Orleans, LA, USA).

Ambrus, J., Robertson, M.J., Yuri Pome, D., Chai, C., Lloyd, J., Whiting, A., Robinson, P.J., McCluskey, A. (2011) The Rhodadyns™ - A New Class of Small Molecular Inhibitors of Dynamin GTPase. 5th International Symposium on Advancing the Chemical Sciences (ISACS 5) – Challenges in Chemical Biology (Manchester, UK).

Bache, N., Larsen, M.R., Robinson, P.J., Graham, M.E. (2011) The regulatory phosphoproteome of synaptic vesicle endocytosis. Gordon Research Conference: Excitatory Synapses & Brain Function, Stonehill College (Easton, MA, USA).

Boutros, R., Perera, S., Gabrielli, B., Robinson, P.J., Chircop, M. (2011) Phosphoregulation of centrin 2 in DNA repair. EMBO Conference: Centrosomes and spindle pole bodies (Barcelona, Spain).

Deane, F., Robertson, M.J., Robinson, P.J., McCluskey, A. (2011) Streamlining the Dynamin Epilepsy Drug Pipeline. 5th International Symposium on Advancing the Chemical Sciences (ISACS 5) – Challenges in Chemical Biology (Manchester, UK).

Graham, M.E., Stone, R.S., Robinson, P.J., Payne, R.J. (2011) Synthesis and chemical biology application of a peptide sequence from clathrin assembly protein AP180 bearing an O-linked β-N-acetylglucosamine-6-phosphate. The 9th Australian Peptide Conference (Hamilton Island, QLD, Australia).

Hizartidis, L., Gordon, C.P., Young, K.A., Deane, F.M., McCluskey, A. (2011) A 3- and 4- component Ugi-Knoevenagel approach to biologically active quinolone-2-(1H)-ones. 5th

pg. 14

International Symposium on Advancing the Chemical Sciences (ISACS 5) – Challenges in Chemical Biology (Manchester, UK).

Moshkanbaryans, L. (2011) Electrical field stimulation of synaptosomes. The Neuroscience and Mental Health Theme, University of Sydney (Sydney, NSW, Australia).

Perera, S. (2011) Development of inhibitors targeting the endocytic proteins, dynamin and clathrin, as a new therapeutic approach for the treatment of cancer. The 5th Barossa Meeting, (Barossa Valley, SA, Australia)

Rao, S. (2011) The Cdk5 regulated phosphoproteome of synaptic vesicle endocytosis. HUPO 10th Annual World Congress (Geneva, Switzerland)

Robertson, M.J., von Kleist, L., Robinson, P.J., Haucke, V., McCluskey, A. (2011) PitstopsTM: a tool to study Clathrin function in cell physiology. 5th International Symposium on Advancing the Chemical Sciences (ISACS 5) – Challenges in Chemical Biology (Manchester, UK).

Robertson, M.J., von Kleist, L., Robinson, P.J., Haucke, V., McCluskey, A. (2011) PitstopsTM: a tool to study Clathrin function in cell physiology. RACI Biomolecular Division Conference: Biomolecular at the Beach (Torquay, VIC, Australia).

Russel, C., Whiting, A., Lloyd, J., Robinson, P.J., McCluskey, A. (2011) Bis-T™ - A New Class of Small Molecular Inhibitors of Dynamin GTPase. RACI Biomolecular Division Conference: Biomolecular at the Beach (Torquay, VIC, Australia).

Sakoff, J. A., Gilbert, J., Tarleton, M., McCluskey, A. (2011) Development of a novel targeted therapy for the treatment of (ER +ve) breast cancer. AACR 2011 (Orlando, Florida, USA).

Sequeira, V., Stehn, J., Haass, N., Schevzov, G., Bonello, T., Guven, K., McCluskey, A., Bischof, L., Palmer, S., Hardeman, E., Allanson, M., Reeve, V., Weninger, W., Gunning, P. Improving the specificity of drugs which target the actin cytoskeleton for cancer therapy. MEPSA 2011 (Brisbane, QLD, Australia).

Sequeira, V., Stehn, J., Schevzov, G., Guven, K., Bonello, T., McCluskey, A., Haass, N., Weninger, W., Palmer, S., Hardeman, E., Allanson, M., Reeve, V., Gunning, P. (2011) Tropomyosin Tm5NM1/2: A Novel Target For Cancer Therapy. ASMR Scientific Meeting, University of Sydney (Sydney, NSW, Australia).

Stehn, J.R., Haass, N.K., Bonello, T., Desouza, M., Kottyan, G., Treutlein, H., Zeng, J., Nascimento, P.R.B.B., Butler, T., Hill, T.A., McCluskey, A., Palmer, S., Hardeman, E.C., Winlaw, D., Weninger, W., Cripe, T.P., Gunning, P. (2011) Developing chemotherapeutics which selectively disable the actin cytoskeleton of tumour cells. AACR EORTC Molecular Targets and Cancer Therapeutics 2011 Meeting (San Francisco, CA, USA).

Stehn, J.R., Haass, N.K., Desouza, M., Sequeira, V., Treutlein, H., Zeng, J., Nascimento, P.R.B.B., Butler, T., McCluskey, A., Palmer, S., Hardeman, E., Winlaw, D., Weninger, W., Gunning, P. (2011) Developing chemotherapeutics which disable the actin cytoskeleton of melanoma cells. International Melanoma Conference (Florida, USA).

Tarleton, M., Sakoff, J.A., Gilber, J., McCluskey, A. (2011) Library synthesis and cytotoxicity of a family of 2-phenylacrylonitriles and discovery of an estrogen dependent breast cancer lead compound. 5th International Symposium on Advancing the Chemical Sciences (ISACS 5) – Challenges in Chemical Biology (Manchester, UK).

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Yang, X. (2011) Quantitative phosphorylation analysis of endocytic proteins during mitosis. 23rd biennial Australian and New Zealand Society for Mass Spectrometry (ANZSMS) Conference (Fremantle, WA, Australia).

Young, K., McCluskey, A. (2011) Utilising technology to streamline the drug development process at the Centre for Chemical Biology Newcastle, Australia. 5th International Symposium on Advancing the Chemical Sciences (ISACS 5) – Challenges in Chemical Biology (Manchester, UK).

Deane, F., Robertson, M.J., Robinson, P.J., McCluskey, A. (2012) Streamlining the Dynamin Epilepsy Drug Pipeline. IUPAC International Conference on Organic Synthesis (ICOS-19) and the Royal Australian Chemical Institute Organic Chemistry Division Conference (RACI-24) (Melbourne, VIC, Australia).

Dyson, L., Wright, A., Robinson, P.J., McCluskey, A. (2012) The Oriodyns - A New Class of Small Molecular Inhibitors of Dynamin GTPase. IUPAC International Conference on Organic Synthesis (ICOS-19) and the Royal Australian Chemical Institute Organic Chemistry Division Conference (RACI-24) (Melbourne, VIC, Australia).

Stehn, J.R., Haass, N.K., Bonello, T., Desouza, M., Kottyan, G., Treutlein, H., Zeng, J., Nascimento, P.R.B.B., Butler, T., Hill, T.A., McCluskey, A., Palmer, S., Hardeman, E.C., Winlaw, D., Weninger, W., Cripe, T.P., Gunning, P. (2012) Developing chemotherapeutics which selectively disable the actin cytoskeleton of tumour cells. American Association for Cancer Research Conference (Chicago, IL, USA).

Yuri Pome, D., Robertson, M.J., Hadzic, G., Hyde, E., Ambrus, J.I., Moshkanbaryans, L., Whiting, A., Robinson, P.J, McCluskey, A. (2012) The RhoadynsTM: a new class of small molecular inhibitors of dynamin GTPase. International Symposium on Advancing the Chemical Sciences (ISACS 6) – Challenges in Chemical Biology (Edinburgh, UK).

Al Otaibi, A., McCluskey, A. (2013) Green chemistry approaches to cytotoxic compounds using Ionic liquid. IDDD (Dubai, UAE).

Al Otaibi, A., McCluskey, A., (2013) The influence of ionic liquids on the Knoevenagel condensation of pyrrole with phenyl acetonitriles. RACI - Biomolecular in the Bush Conference (Leura, VIC, Australia).

Ambrus, J.I., Yuri Pome, D., Robertson, M.J., Chau, N., Whiting, A., Robinson, P.J., McCluskey, A. (2013) The Rhodadyns: a new class of dynamin inhibitor. RACI - Biomolecular in the Bush Conference (Leura, VIC, Australia).

Chan, L., Janakan, V., Graham, M.E. (2013) An optimized workflow for defining the molecular interactions of clathrin assembly proteins. 18th Lorne Proteomics Symposium (Lorne, VIC, Australia).

Cossar, P., McCluskey, A. (2013) Application of flow hydrogenation to medicinal chemistry. RACI - Biomolecular in the Bush Conference (Leura, VIC, Australia).

Hizartidis, L., Tarleton, M., Gordon, C.P., McCluskey, A. (2013) Chemoselective flow hydrogenation approaches to highly decorated 7-oxa-bicyclo[2.2.1]heptanes. 5th Conference on Frontiers in Organic Synthesis Technology (Budapest, Hungary).

Lin, A.J.S., Deane, F., Robinson, P.J., McCluskey, A., (2013) An expedient and robust synthesis of solid-supported chemical biology probes. RACI - Biomolecular in the Bush Conference (Leura, VIC, Australia).

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Miller L. (2013) Isolating the Bulk Endosome from Nerve Terminals. 13th Hunter Cell Biology (Pokolbin, NSW, Australia).

Russell, C., Deane, F., McCluskey, A. (2013) Ellipticine and Analogues by Flow Chemistry. RACI - Biomolecular in the Bush Conference (Leura, VIC, Australia).

Sauer, S., Hauke, V., Robinson, P.J., McCluskey, A. (2013) Smart Drug Design and Library Synthesis of Clathrin Based Inhibitors. RACI Biomolecular Division Conference: Biomolecular at the Beach (Torquay, VIC, Australia).

Sequeira, V.B., Stehn, J.R., Haass, N.K., Bonello, T., Desouza, M., Swain, A.L., Wang, B., Hook, J., Schevzov, G., Treutlein, H., Zeng, J., Nascimento, P.R.B.B., Butler, T., McCluskey, A., Palmer, S., Hardeman, E., Winlaw, D., Reeve, V., Weninger, W., Gunning, P. (2013) A novel class of compounds which disrupt the actin cytoskeleton of melanoma cells. Society for Melanoma Research (Philadelphia, PA, USA).

Sequeira, V.B., Stehn, J.R., Haass, N.K., Bonello, T., Desouza, M., Swain, A.L., Wang, B., Hook, J., Schevzov, G., Treutlein, H., Zeng, J., Nascimento, P.R.B.B., Butler, T., McCluskey, A., Palmer, S., Hardeman, E., Winlaw, D., Reeve, V., Weninger, W., Gunning, P. (2013) Selectively disrupting the actin cytoskeleton of melanoma cells with a novel class of compounds. MEPSA (Mutagenesis and Experimental Pathology Society for Australasia) in conjunction with the Asia and Oceania Congress on Photobiology (Sydney, NSW, Australia).

Chan, L., Moshkanbaryans, L., Xue, J., Graham, M.E. (2014) Identification of an essential clathrin interaction sub-domain at the C-terminus of clathrin assembly protein AP180. Cell Biology of the Neuron, Gordon Research Conference, Waterville Valley Resort, (Waterville Valley, NH, USA).

Horatscheck, A., Miksche, S., Perepelittchenko, L., Robertson, M.J., Seyffarth, C., Bulut, H., Fink, U., Stahlschmidt, W., von Kleist, L., Oder, A., McCluskey, A., Nazare, M., Haucke, V. (2014) SAR Studies on Pitstop 2, an inhibitor of clathrin mediated endocytosis. European Federation of Medicinal Chemistry, XXIII International Symposium on Medicinal Chemistry (Lisbon, Portugal).

Services to Research: Symposia hosted by ACRF-CFK

1st Chemical Proteomics Symposium 20th June 2013 Hosted by the ACRF Centre for Kinomics Held at CMRI (Westmead, Australia)

Invited Speakers

Dr Mark Graham Protein Biochemistry Group Leader, Children’s Medical Research Institute. Chemical proteomics approach for determining a glycosylphosphorylation-regulated protein function. Professor Adam McCluskey

pg. 17

Professor of Chemistry & Director, Centre for Chemical Biology, University of Newcastle, Australia. Identification of ciliopathy genes in humans and mice Professor Marc Wilkins Director, Ramaciotti Centre for Gene Function Analysis and NSW Systems Biology Initiative; Professor, School of Biotechnology and Bimolecular Sciences, University of New South Wales. The dynamics of protein interaction networks. Professor Roger Daly Head, Department of Biochemistry and Molecular Biology, Monash University Tyrosine kinase signalling networks in human cancer. Professor Tony Purcell Head of Quantitative Proteomics, Immunproteomics Laboratory, Department of Biochemistry and Molecular Biology, Monash University Big and small: chemical interference with immune receptor ligand interactions explains many adverse drug reactions Associate Professor Mark Molloy Australian Proteome Analysis Facility (APAF) Director, Macquarie University Experiences with a Bisindolylmaleimide chemical probe in cancer cells and tissues Associate Professor Mark Raftery Director, Bioanalytical Mass Spectrometry Facility, University of New South Wales Mass Spectrometry and Chemical Proteomics Associate Professor Sally-Ann Poulsen Chief Investigator, Chemical Biology, Eskitis Institute for Cell and Molecular Therapies & Manager, Fourier Transform Mass Spectrometry (FT-MS) Facility, Griffith University Labelling and detection of biomolecules in cells using click chemistry Associate Professor Stuart Cordwell Associate Professor, School of Molecular Bioscience, Charles Perkins Centre, and the Discipline of Pathology, School of Medical Science, The University of Sydney. Functional decoration: post-translational modifications and their crosstalk in myocardial ischemia/reperfusion injury.

Abstract Presenters

Dr Fiona Deane Research Associate, School of Environmental and Life Sciences, Faculty of Science and Information Technology, University of Newcastle, Australia. Design, synthesis and evaluation of Clickbeads.

pg. 18

Associate Professor Clare Hawkins Group Leader, Inflammation Group, Heart Research Institute Cellular targets of the myeloperoxidase-derived oxidant hypothiocyanous acide (HOSCN): Evidence for reversible protein thiol modifications. Jordan Basnett PhD Student, Centre for Cancer Research, Westmead Millennium Institute, University of Sydney Global Proteome Analysis of Acute Lymphoblastic Leukaemia Cells Resistent to MTOR Inhibition

by Everolimus.

Services to Research: Selected Workshops & Seminar Series hosted by ACRF-CFK

1. Chris Hodgkins, AB SCIEX, AU & NZ , Kinomics: The Rise of the Machines, Two- day workshop, 16-17th October 2012,

2. Dr Katie Southwick, Thermo Fisher Scientific, Florida USA, Fundamentals and Tricks for Post Translational Modifications Analysis with Mass Spectrometry – The utility of multiple fragmentation techniques – CID/HCD/ETD, Proteomics Seminar Series, 31st January 2014

3. Dr Stephen Tate, AB SCIEX, Toronto, Mapping differential interactomes by affinity purification coupled with data-independent mass spectrometry acquisition Proteomics Seminar Series, 13th February 2014

4. Dr Paul Goulding, Nonlinear Dynamics, UK, Discovery proteomics analysis: How to ensure you get the maximum "bang for your buck" from your analysis hardware Thursday 20th February 2014

pg. 19

Appendix A: Media Coverage and Photographs

Official ACRF CFK Launch. 27 September 2012.

ACRF Chairman Tom Dery presenting a cheque to Lorimer Dods Professor and Director Roger Reddel.

27 September 2012.

pg. 20

At the ACRF CFK Launch (L-R): Lorimer Dods Professor and Director Roger Reddel, Professor Phil

Robinson (CMRI), Professor Adam McCluskey (University of Newcastle), Dr Valentina A Valova

(Manager, Biomedical Proteomics and the ACRF Centre for Kinomics), Ed Husic MP, Virginia Judge

(National Manager, Strategic Partnerships and Capital Works Program, CMRI). 27 September 2012.

Professor Phil Robinson (Director, ACRF Centre for Kinomics; Head of Cell Signalling Unit, CMRI)

presents at the launch of ACRF Centre for Kinomics. 27 September 2012.

pg. 21

CMRI is visited by the former Governor General of Australia, The Honourable Dame Quentin Bryce

AD CVO, who stopped by to view the soon-to-be-opened ACRF CFK. L-R: The Honourable Dame

Quentin Bryce AD CVO, Professor Phil Robinson (Director, ACRF Centre for Kinomics; Head of Cell

Signalling Unit, CMRI), Dr Valentina Valova (Manager, Biomedical Proteomics and the ACRF Centre

for Kinomics), Dr Annie Quan (Cell Signalling Unit, CMRI). 2 February 2012.

CMRI is visited by the former Governor General of Australia, The Honourable Dame Quentin Bryce

AD CVO, who stopped by to view the soon-to-be-opened ACRF CFK. Professor Phil Robinson hosts

the Governor General. 2 February 2012.

pg. 22

ACRF CFK hosted the 1st Chemical Proteomics Symposium at CMRI, which was sponsored by a

number of vendors who work closely with ACRF CFK. This Symposium is set to become a biannual

event that brings together researchers from across Australia who work in or are interested in using

chemical proteomics in their own projects or programs. 20 June 2013.

Professor Tony Purcell (Head of Quantitative Proteomics, Immunproteomics Laboratory, Monash

University) presents at the 1st Chemical Proteomics Symposium. 20 June 2013.

pg. 23

The Symposium presented an opportunity for PhD students and research staff to meet with

renowned proteomics researchers and industry experts. 20 June 2013.

One of the mass spectrometers purchased with generous funding from ACRF.

pg. 24

Professor Adam McCluskey, co-director of ACRF CFK, in the medicinal chemistry laboratory at the

University of Newcastle, Australia.

ACRF CFK moved into its new custom-designed facility space in CMRI’s new building extension in

October 2014. This is the entrance to the facility. November 2014.

pg. 25

ACRF CFK moved into its new custom-designed facility space in CMRI’s new building extension in

October 2014. This highly specialised space removes any contaminants that may affect samples

processed by the mass spectrometers. November 2014.

Dr Kasper Engholm-Keller (Visiting Postdoctoral Fellow, University of Southern Denmark) prepares

samples to be processed by one of the mass spectrometers housed at ACRF CFK.

MEDIA RELEASE

NEW CENTRE PROPELS AUSTRALIA TO FOREFRONT OF CANCER RESEARCH

27 September 2012, Sydney: In an Australian first, a new centre dedicated to the research of ‘Kinomics’ is to be launched in Sydney, giving Australian scientists hope of unlocking some of the mysteries surrounding diseases such as cancer, cardiovascular disease, asthma and neurodegenerative disorders. The centre has received significant funding ($3.1 million) from the Australian Cancer Research Foundation (ACRF). A joint venture between the Children’s Medical Research Institute (CMRI) and the University of Newcastle (UoN), the Australian Cancer Research Foundation Centre for Kinomics (ACRF-CFK) will provide researchers with an entirely new way of understanding and improving therapeutic drugs. Working in collaboration, these teams of scientists will embark on a journey to understand the Kinome—the subset of proteins known as protein kinases. Protein kinases are “master switches” that control most normal cell functions in the body and are considered to be the cancer drug target of the 21st century. Humans have 518 protein kinases, and errors in kinases contribute to at least 400 different diseases, including cancer, neurological conditions, cardiovascular diseases, inflammatory conditions, and asthma. Health Minister Tania Plibersek says the centre puts Australia on the world map for research and development into disease prevention and treatment. “This facility offers hope to patients and families living with diseases where there is neither cure nor effective treatment. The research conducted has the potential to improve the future health of Australians and people around the world,” Ms Plibersek says. The brainchild of CMRI Professor Phil Robinson and Professor Adam McCluskey from UoN, who have been working together for the past decade, the Centre for Kinomics will be based at CMRI in Westmead and the University of Newcastle. Professor Robinson says, “The Centre will also enable our scientific teams to better understand current cancer therapies and reasons for their unwanted side effects, as well as to develop new drugs for a multitude of human diseases, many of which are currently without any effective treatment.” “One of the things that’s always been at the back of our minds is: If you give someone a drug, there’s going to be side effects, and that’s one of the things that slows the drug development pathway down immensely,” says McCluskey. “You’ve got to try to figure out exactly where it’s hitting: is it hitting a good target or is it hitting a bad target?” “We are confident that this new ACRF Centre for Kinomics will propel scientific discovery in Australia to the forefront of global research,” says Robinson. “But our real hope is we will come up with better drugs and better therapeutics for cancer patients and other indications.”

Tom Dery, Chairman of the Australian Cancer Research Foundation, which contributed $3.1 million dollars to develop the new centre says, “We believe strongly in the vision and the skills of Professor Robinson and Professor McCluskey, and have put our name and money behind the new centre, which we expect to help with ACRF’s ultimate goal, which is to find the cures for cancer.”

ENDS

About Children’s Medical Research Institute: Children’s Medical Research Institute conducts fundamental research to understand the genes

involved in human health and development and the underlying causes of disease. CMRI is at the

forefront of international research in the areas of embryonic development and birth defects, cancer,

nerve cell signalling, and gene therapy. CMRI is also a member of the Kids Cancer Alliance, which is

committed to speeding up development of new cancer therapies for children and bringing those

therapies to clinics in both urban and rural areas. Find out more at www.cmri.org.au. This not-for-

profit institute is funded by competitive grants, a community of supporters and Jeans for Genes Day

Friday August 3 – for which you can volunteer. Visit www.jeansforgenes.org.au. The CMRI arm of the

Centre for Kinomics is directed by Prof Phil Robinson.

About The Australian Cancer Research Foundation

The Australian Cancer Research Foundation (ACRF) is dedicated to helping find the cures for cancer

through continued funding for world-class cancer research in Australia. Learn more at

www.acrf.com.au.

About the University of Newcastle

The University of Newcastle houses the medicinal chemistry laboratory in the Discipline of Chemistry,

overseen by ACRF-CFK Co-Director Adam McCluskey.

Media enquiries contact: Eliza Newton 02 8281 3252 OR Emma Pearson 02 8281 3233

      

Community Information Fact Sheet  What is Kinomics?  Kinomics is the study of the Kinome – a subset of proteins known as protein kinases.  These act as the “master switch” for many normal cell functions in the body and are considered to be the cancer drug target of the 21st century.  There are 518 protein kinases in the human body, and errors in these kinases contribute to around 400 different diseases, including cancer, neurological conditions, cardiovascular diseases, inflammatory conditions and asthma.     Protein kinases are the target of many current therapeutic drugs that treat these conditions, and the research undertaken at the new Australian Cancer Research Foundation Centre for Kinomics will analyse existing drugs as well as develop new, more effective treatments.    What is the Australian Cancer Research Foundation Centre for Kinomics?  The Australian Cancer Research Foundation Centre for Kinomics (ACRF‐CFK) is a joint venture between Children’s Medical Research Institute (CMRI) and the University of Newcastle (UoN).  The centre is funded by grants from the Ramaciotti Foundation and the Australian Cancer Research Foundation of $1 million and $3.1 million, respectively.    The centre is the brainchild of CMRI Professor Phil Robinson and Professor Adam McCluskey from UoN who have been working together for the past decade.  The research work undertaken at the centre will build upon this long standing collaboration between protein kinase experts from the CMRI and medicinal chemists from UoN, as well as CMRI's expertise in cancer research.  What is the aim of the Australian Cancer Research Foundation Centre for Kinomics and why is it so important to Australian medical research?  The establishment of the ACRF‐CFK is an Australian first that will provide researchers with an entirely new way of understanding and improving therapeutic drugs.  The ACRF‐CFK’s purpose‐built laboratories, housed at the CMRI and UoN, will allow scientists to better understand the Kinome and benefit a wide range of medical research programs throughout Australia.  The centre will also enable better understanding of current therapies and their unwanted side effects, as well as the development of new drugs for a multitude of human diseases, many of which are currently without any effective treatment.  What facilities are available for researchers interested in Kinomics?  The new facility will benefit medical researchers throughout Australia. The ACRF and Ramaciotti awards support a broad collaboration, led by CMRI and UoN, which involves three universities, five medical research institutes, and a total of 23 medical research teams across NSW. The ACRF award also widened the collaboration even further to involve cancer research teams throughout the nation, all of which can employ the centre’s facilities for their projects.  

UoN houses the flow chemistry laboratory, where they have developed KinoClick™ beads, a new tool for direct profiling of cellular kinases. CMRI houses a mass spectrometry (MS) laboratory to undertake initial evaluation and optimization of KinoClick™ beads, perform quality control and sample analysis for collaborating research teams.  What is mass spectrometry?  Mass spectrometry (MS) is the single most powerful analytical technique that underpins all modern day biomolecular science. It measures molecules to determine their weight, thus facilitating the identification and characterisation of key components in biological processes (proteins, peptides, carbohydrates, DNA, drugs). MS is the best approach for studying the master controls governing basic cell behaviour and how they malfunction in a range of diseases.  What are KinoClick™ beads?  KinoClick™ beads are broad‐spectrum protein kinase inhibitors that are physically attached to plastic beads, allowing near complete extraction of the kinome and rapid analysis by mass spectrometry. This rich source of information has major biological relevance, providing for the first time a near complete and quantitative profile of the protein kinases present in a particular cell or tissue sample at any point in time. It is a revolutionary platform technology, requiring a new mind‐set and opening new research directions. KinoClick™ beads are not commercially available and their manufacture requires specialised medicinal chemistry equipment and expertise to prepare.   Which organisations administer the new Australian Cancer Research Foundation Centre for Kinomics?  Children’s Medical Research Institute: Children’s Medical Research Institute conducts fundamental research to understand the genes involved in human health and development and the underlying causes of childhood disease. CMRI is at the forefront of international research in the areas of embryonic development and birth defects, cancer, nerve cell signalling, and gene therapy. As many diseases that affect children have the same origins in adults, the biomedical research performed at the CMRI has the potential to improve the future health of people of all ages.  Professor Phil Robinson, Head of the Cell Signalling Unit at the CMRI and Senior Principal Research Fellow of the National Health Medical Research Council, established the Centre of Kinomics in conjunction with the University of Newcastle’s Professor Adam McCluskey.  University of Newcastle: The Centre for Kinomics at the University of Newcastle is led by Professor Adam McCluskey in the Discipline of Chemistry. This arm of the centre has helped pioneer a new approach for direct profiling of cellular kinases, a multi‐million dollar initiative providing a unique service to research teams throughout Australia.   

M E D I A C O V E R A G E

Outlet/publication type Number of articles/ coverage reported

Television 1

Radio 2

Online 1

Blog 1

Trade 1

Total Coverage 6

M E D I A C O V E R A G E S U M M A R Y

Publication Date Region Audience reach

Television

Channel Ten News 27/09/12 Sydney & Adelaide 240,00

Radio

4WK Toowoomba 27/09/12 Toowoomba, NSW 192,980

2SM 2709/12 Sydney, MSW 55,000

Online

Parramatta Advertiser Online 4/10/12 Sydney, NSW 115,000

Blog

Parra Mattas N/A Sydney, NSW N/A

Trade

Australian Life Scientists 28/09/12 National 7,053

Total 610,033

To: Children’s Medical Research Institute

From: Ogilvy PR Health

Re: Media Coverage Report - Kinomics Centre Launch

Cc:

Date: 13/12/12 Status: Confidential

Sheryl Taylor reports: Scientists say they're steps away from coming up with the best cancer drugs of the century. A new research centre in Sydney will bring together teams from across the nation. The centre will target kynomics, the master switches that control most cells in the body and are linked to hundreds of diseases. The Australian Cancer Research Foundation has given more than $3 million for world class equipment.

Outlet: Channel Ten News Speaker: Sheryl Taylor

Date: 27/09/12 Page/time: 5.00pm

Region: Sydney & Adelaide Audience reach : 240,000

Newsreader: A new centre for the research of Kinomics will be launched in Sydney today. Phil Robinson, Head, Children's Medical Research Institute Unit, says that this type of research has made a reduction in many cancers.

Newsreader: A new centre dedicated to the research of Kinomics will be unveiled in Sydney today. Professor Phil Robinson, Children's Medical Research Institute Unit Head, cites this research has impacted in the reduction of many cancers.

Outlet: 4WK Toowoomba Speaker: N/A

Date: 27/09/12 Page/time: 6.01am

Region: Toowoomba, NSW Audience reach : 192,980

Outlet: 2SM Speaker: N/A

Date: 27/09/12 Page/time: 6.31am

Region: Sydney, NSW Audience reach : 55,000

Outlet: Parramatta Adviser Online Speaker: N/A

Date: 4/10/12 Page/time: N/A

Region: Sydney, NSW Audience reach : 115,000

Outlet: Australian Life Scientist Speaker: Tim Dean

Date: 28/9/12 Page/time: 12.38

Region: Parramatta, NSW Audience reach : 7,053

M E D I A C O V E R A G E

Outlet/publication type Number of articles/ coverage reported

Print 3

Radio 1

Total coverage 4

M E D I A C O V E R A G E S U M M A R Y

Publication Date Region Audience reach

Print

Hills News 20/11/12 Sydney, NSW 73,000

Parramatta Sun 15/11/12 Sydney, NSW 78,000

Parramatta Advertiser 14/11/12 Sydney, MSW 115,000

Radio

WS FM 12/11/12 Sydney, NSW 72,000

Total 338,000

To: Children’s Medical Research Institute

From: Ogilvy PR Health

Re: Media Coverage Report - CMRI expansion, official “turning of the sod”

Cc:

Date: 13/12/12 Status: Confidential

Outlet: Hills News Speaker: Jade Wittmann

Date: 20/11/12 Page/time: 8

Region: Sydney, NSW Audience reach : 73,000

Outlet: Parramatta Sun Speaker: Jade Wittmann

Date: 15/11/12 Page/time: 4

Region: Sydney, NSW Audience reach : 78,000

Outlet: Parramatta Adviser Speaker: Di Bartok

Date: 14/11/12 Page/time: 18

Region: Sydney, NSW Audience reach : 115,000

Newsreader: An expansion of the Children's Medical Research Institute at Westmead has been announced. Roger Reddel, Director, Children's Medical Research Institute says it will help with research into cancer, birth defects and gene therapy.

Outlet: WS FM Speaker: N/A

Date: 12/11/12 Page/time: 8.02am

Region: Sydney, NSW Audience reach : 72,000

TweetAMRITSAR: Contemporary life style and prevailing tension was the cause for increasing neurodiseases all over the world , said Prof Phillip J Robinson of Children Medical Research Institute,NSW,Australia while delivering his special lecture at the second day of 30th Indian Academy ofNeurosciences meet held at Guru Nanak Dev University on Sunday. Robinson said that socialsupport and sympathy were required for patients of depression.

He said that many scientists all over the world were doing research on neuro diseases and hoped that they would discover suitable treatment forneuro patients.He said that Epilepsy (Recurrent Seizures) in children was curable. He also stressed upon the use of Dynamin inhibitors as atreatment for epilepsy. He said that epilepsy arises in children due to myelination. He said that epilepsy was found in 90% of developingcountries. In India, 70% cases occur in rural areas. He suggested that the cooperative and loving attitude of parents, teachers and society couldhelps the children to respond well.

Lifestyle and tension causes neuro diseaseYudhvir Rana, TNN | Oct 28, 2012, 05.22PM IST

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Home » Spot News » Looking into reasons for Neuro Disorders

AMRITSAR: Neurosciences problems are not only in India but it is a global issue so the subject expertsfrom all over the world should come together on a single platform to resolve this issue. An awarenesscampaign regarding this is the need of hour.

These views were expressed by renowned Neurosurgeon, Prof. A.K. Mahapatra, Director of AIIMS atBhubaneswar and Prof. Phillip J Robinson of Children Medical Research Institute, NSW from Australiawhile addressing the media-person here today in the Committee Room of the Guru Nanak Dev University.

This press conference was organized by the Department of Biotechnology at the eve of 30th IndianAcademy of Neurosciences meet and an International Symposium with the theme ‘TranslationalNeurosciences: Unraveling Mysteries of Brain in Health and Disease’ which is being organized fromOctober 27th to 30th, 2012 by the Guru Nanak Dev University.

Dr. T.R. Laxmi from Department of Neurophysiology, National Institute of Mental Health and NeuroSciences, Bangalore; Dr. G.N. Pandey from Department of Psychiatry, University of lllionis, Chicago; Dr.B.N. Dhawan from CDRI, Lucknow; Prof. Subrata Sinha from NBRC, Manesar; Dr. Sarah Dunlop fromUniversity of Western Australia and Organizing Secretary, Dr. Gurcharan Kaur were also present.

Prof. Mahapatra said that contemporary life styles along with lack of awareness are the major reason fromneuro disorders. He said that the major cause of depression among youth is lack of social bounding whichsome times leads them towards the tendency of suicide.

He said that the need of hour is to create awareness among masses about the neuro diseases. He said thatmore and more doctors are also need to trained in this regard. He said that during depression medicineshould be avoided instead proper counseling from trained Psychiatrist should be encouraged.

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He said that research in brain is still in its juvenile stage and the neuro aspects for therapeutics have to beexplored. He talked about translational medicine which basically refers to research done in lab translatedinto medical health for patients. He drew attention to the Indian scenario where research is still a thrustarea for the government and there is lack of corporate involvement in it.

He said that the brain health and disease is not given its due share of importance inIndiajust as cancer andheart disease is highlighted.

Prof. Robinson said that the financial crunch is not only but is all over the world. He said that the solutionto neuro problems should be soughed with the help of the scientists all over the world. He also suggestedthat the qualified doctors should come forward for further research in neuro science.

He said that all funding involved in research work is generated from public, so, this needed that theresearch results and benefits should be ensured to reached general masses. He also advocated properresearch for proper treatment.

While talking about the stem cell therapy, Prof. Sinha said that the research form stem cell is still underprocess which is needed to regenerate the capacity of brain cells but some private organizations aregenerating money by miss guiding general masses.

Prof. Gurcharan Kaur stressed on the fact that this conference was a very strong effort to bring togethersome 300 budding future scientists and organization on a scale of 20 sessions including 40 chairpersonswho will present their summary on the last day of the meet which will be heard over by the DBT advisorand this would lead to fund re-allocation in neuroscience.

She pleaded the media to deliver this message to the masses that basic research and translationalneurosciences, hand in hand, are required to provide awareness about neuro health.

Dr. Pandey highlighted the neuro health disorders like depression, suicidal patterns increasing among theyouth and old alike. He advocated a holistic approach and compared the approach variance between adeveloped nation, like theUSA, and a developing nation, likeIndia. The key focal area remained researchand investment into basic sciences and translating this for public welfare.

Dr. Dhawan laid emphasis on various brain disorders and the difference of government and privateattitudes to brain disorders. Prof. Subrata Sinha drew special attention to nervous disorders in kids likeautism, dyslexia and cerebral palsy.

Dr. Sarah Dunlop rooted for public participation and awareness into neuroscience research and discussedthat events like science congress should be held more often so that the public awareness is enhanced.

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CMRI scientists discover control point for neuron branching and brain developmentScientists at Children’s Medical Research Institute (CMRI), Annie Quan and Prof Phil Robinson, have identified a specific site in the protein Syndapin I that controls nerve cell (neuron) outgrowth, a discovery that provides a better understanding of brain and spinal cord development. Their work was published in the prestigious journal, Proceedings of the National Academy of Sciences (USA), in February.

In the brain, neurons are the cells responsible for learning, memory and emotions, and form the control centres for the human body. To achieve this, they make an extensive network of connections between each other during development and continuing on into the first years after birth. The connection process involves the cells actively growing protrusions or ‘arms’ called neurites, which extend long distances across the brain to form its ‘wiring’.

Ms Quan and Prof Robinson found that a single site on the Syndapin I protein (called T181) can be modified to increase or decrease neurite outgrowth.

The identification of a single control point with such influence over neuron growth and shape means CMRI scientists now have a target to aim at when developing therapeutic drugs that may one day help treat or prevent some birth defects involving the brain or spinal cord.

Representatives of the Australian Cancer Research Foundation (ACRF), including their CEO David Brettell, presented Children’s Medical Research Institute (CMRI) with a cheque in April, the first instalment towards more than $3 million of funding ACRF has committed to help develop a new research centre at CMRI. The centre is also supported by $1 million from The Ramaciotti Foundation.

The Australian Cancer Research Foundation Centre for kinomics (ACRF-CFk) – a joint

venture between CMRI and the University of Newcastle – is an Australian first that will provide an entirely new approach to the understanding of cancer therapeutic drugs and ways to improve them.

The cheque was presented by Mr Brettell during a celebration in honour of the new centre. ACRF representatives met the scientists and key organisers involved, and toured the CMRI arm of the centre’s facilities, which will be significantly improved and expanded by

completion of the first stage of CMRI’s building re-development in 2014.

AB Sciex (who are long time supporters of CMRI and Jeans for Genes®) generously sponsored the celebration.

The ACRF-CFk, which will provide a resource for cancer researchers across Australia, officially opens in September and will be featured in the next edition of Under the Microscope.

CMRI celebrates funding for ACRF Centre for KinomicsPhil Robinson (Co-Director ACRF-CFK), Valentina Valova (Manager ACRF-CFK), Adam McCluskey (Co-Director ACRF-CFK), David Brettell (CEO of ACRF), Patrick Tam (Deputy Director CMRI)

CMRI PhD students Lia Moshkanbaryans and Annie Quan

CMRI supports new electron microscope lab at WestmeadThe NSW Minister for Health and Minister for Medical Research, Jillian Skinner, and the Member for Parramatta, Geoff Lee, opened the redesigned Electron Microscope Laboratory at Westmead Hospital’s Institute of Clinical Pathology and Medical Research (ICPMR) in May.

Children’s Medical Research Institute (CMRI) was one of the sponsors of the Electron Microscope Laboratory, which is a joint project of the ICPMR and the Westmead Research Hub.

Professor Reddel, Director of CMRI, said, “This facility will be a resource for CMRI researchers and for scientists and clinicians across the Westmead campus.”

The relocation and refurbishment of the laboratory was also sponsored by: The ICPMR Staff Specialists’ Private Practice Partnership; Western Sydney Local Health District Research and Education Network; and Westmead Millennium Institute for Medical Research.

“The electron microscope can identify viruses that are difficult to diagnose by conventional methods,” Mrs Skinner said.

The current work of the laboratory will particularly benefit people with conditions like kidney disease, unusual tumours and some respiratory disorders. The laboratory will also assist new research into many other diseases.

Trish Fortier, Barbara Whittaker, Larrisa Ware and Alison Elms

FeaturesDirector’s Desk 2

ALT Discovery 2

Royal reception 2

Sod Turning 3

Woolworths partnership 3

Star Alliance scholarship 3

Jeans for Genes Day recap 4

Gala Dinner 4

Race Day 4

Inspiring scientists 5

Message from Marissa 5

Committees and supporters 6

Healthier Kids, Brighter FuturesChildren’s Medical Research Institute (CMRI) is an independent organisation committed to unlocking the mysteries of childhood disease. Our scientists investigate conditions such as birth defects, cancer and epilepsy. Our philosophy is that major advances in prevention and treatment come from research into the fundamental processes of life. Our work is made possible by our community of supporters and Jeans for Genes®.

Locked Bag 23 Wentworthville NSW 2145

Tel 02 8865 2800 Fax 02 8865 2801

Freecall 1800 436 437

Email info@cmri.org.au Website www.cmri.org.au

© CMRI 2013

ACRF Centre for Kinomics provides new hope for cancer treatment

Tom Dery, Adam McCluskey, Valentina Valova,

Phil Robinson, Roger Reddel and Ed Husic MP

The newsletter of Children’s Medical Research Institute Summer 2013

under the micr scope

Frederick Bellette and mum, Kate Merry

Thanks to significant funding from the Australian Cancer Research Foundation (ACRF), Ramaciotti Foundations and ongoing donations from our supporters, Children’s Medical Research Institute (CMRI) launched a new centre in September dedicated to the research of ‘Kinomics’. This Australian first will help scientists unlock some of the mysteries surrounding diseases such as cancer, cardiovascular disease, asthma and neurodegenerative disorders.

A joint venture between CMRI and the University of Newcastle (UoN), the Australian Cancer Research Foundation Centre for Kinomics will provide researchers with an entirely new way of understanding and improving therapeutic drugs.

The centre is the brainchild of CMRI’s Professor Phil Robinson and Professor Adam McCluskey from UoN. Working in collaboration with scientists across Australia, they will embark on a journey to understand the Kinome—the subset of proteins known as protein kinases. Protein kinases are “master switches” that control most normal cell functions in the body and are considered by many to be the cancer drug targets of the 21st century.

Humans have 518 protein kinases, and errors in kinases contribute to at least 400 different diseases, including cancer, neurological conditions, cardiovascular diseases, inflammatory conditions, and asthma.

Health Minister Tanya Plibersek says the centre puts Australia on the world map for research and development into disease prevention and treatment.

“This facility offers hope to patients and families living with diseases where there is neither cure nor effective treatment. The research conducted has the potential to improve the future health of Australians and people around the world,” Ms Plibersek says.

Kate Merry, whose one year old son Frederick is currently undergoing chemotherapy for a sarcoma in his leg, attended the opening. “I was excited to learn this sort of research is going on,” Ms Merry says. “It gives our family hope that there will be better treatments one day, if not for Freddy then for other children.”

Tom Dery, Chairman of the Australian Cancer Research Foundation, which contributed $3.1 million dollars to develop the new centre says, “We believe strongly in the vision and the skills of Professor Robinson and Professor McCluskey, and have put our name and money behind the new centre, which we expect to help with ACRF’s ultimate goal, which is to find the cures for cancer.”

Features

Major Discoveryin Cancer Research 2

New Building Plans Approved 3

Jeans for Genes 4

Earle Page Run30th Anniversary 5

Discovery Partners 5

Committee Power andDates for your Diary 6

Today’s scientists for tomorrow’s children

The Children’s Medical Research Institute (CMRI) is an independent organisation committed to unlocking the mysteries of disease. Our scientists investigate conditions such as birth defects, cancer, and epilepsy. Our philosophy is that major advances in prevention and treatment come from research into the fundamental processes of life. Our work is made possible by our community of supporters and Jeans for Genes®.

The newsletter of the Children’s Medical Research Institute Summer 2009

Produced by the Fundraising & Community Relations Department, Children’s Medical Research Institute

Locked Bag 23 Wentworthville NSW 2145

Tel 02 9687 2800 Fax 02 9687 2120 Freecall 1800 GENIES (436 437)

Email info@cmri.org.au Website www.cmri.org.au

© CMRI 2009

With two exciting announcements for major funding in November 2009, Children’s Medical Research Institute (CMRI) has secured the means to move full steam ahead with the development of a world-first facility which will bring together state-of-the-art instrumentation, personnel and expertise to enable an entirely new approach to the understanding of therapeutic drugs and ways to improve them.

The grants of $3.1 million and $1 million respectively from the Australian Cancer Research Foundation (ACRF) and the Ramaciotti Foundations will enable the establishment of the ACRF Chemical Proteomics Centre for Kinomics (CFK) supported by Ramaciotti at CMRI and the University of Newcastle (UoN).

The CFK will enable the new discipline of kinomics, not yet available in Australia, to be used in a completely novel drug design strategy. It will enable better understanding of current therapies and their unwanted side effects, as well as the development of new drugs for a multitude of human diseases, many of which are currently without any suitable treatment.

Continued page 3...

The Centre for Kinomics (Ramaciotti/ACRF)

A World First

L to R: Professor Adam McCluskey, CMRI Board Members Professor Frank Martin and Mrs Carolyn Forster, CMRI Director

Professor Roger Reddel and Professor Phil Robinson at the Ramaciotti Awards Dinner after the announcement of the

Biomedical Research Award for the CFK

under the micr scope

Building plans get Minister’sstamp of approvalChildren’s Medical Research Institute (CMRI) often refers to its

dedicated researchers as “Today’s Scientists for Tomorrow’s Children”.

The research excellence which has led to major discoveries in the

areas of cancer, epilepsy, birth defects and gene therapy is the

result of world class scientists being supported by a clear vision of

the importance of research into the fundamental processes of life.

But CMRI is very aware of the need for much more work in all of

these areas, and has begun the planning that will underpin a major

expansion of our research activities.

CMRI presently accommodates 120 research scientists in twelve

laboratories, supported by 30 administration, fundraising, and scientific

support staff. In 2008, CMRI’s Board decided that the Institute should

substantially increase its research activities by recruiting many more

top scientists in all of CMRI’s existing areas of international research

excellence, and to build the laboratory space and facilities needed

to make this possible. The planning process was overseen by CMRI’s

Operations Manager, Greg Craig, who inspected leading research

facilities internationally. Dale Swan, from architectural firm Ancher,

Mortlock and Woolley who designed our existing building were

given the task of planning facilities suitable for the next generation

of cutting-edge CMRI research. Together, they have developed a

5-stage, 7-year building program, that will deliver a world-class,

energy-efficient “green” building capable of accommodating 500

research scientists,with maximum flexibility and functionality, without

major disruptions to the ongoing research work in the meantime.

The building plans have now been fully evaluated and approved by

the NSW Department of Planning. The quality of the plans and the

submitted documents was so high that full approval was able to

be given less than four months after submission. In October 2009,

the then NSW Minister for Planning and now NSW Premier Kristina

Keneally, accompanied by the Minister assisting the Minister for Health

(Mental Health and Cancer), Barbara Perry, visited CMRI to tour CMRI’s

existing facilities, and announce her Department’s approval of the

expansion plans.

A project of this scope will inevitably require government funding to

help make it a reality. CMRI was therefore very disappointed to be

informed by the Commonwealth Government that the rules relating

to the nation-building funds were inadvertently written in such a way

that they exclude applications from medical research institutes that

do long-term basic research into the underlying causes of disease.

Despite this major setback, CMRI will explore other ways of funding

its planned building, and is keenly anticipating the many exciting

opportunities this will bring towards the ultimate goal of improving

the health of future generations of children.

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The new facility will benefit medical researchers throughout

Australia. The Ramaciotti award supports a collaboration

led by CMRI and UoN, and involving three universities,

five medical research institutes, and a total of 23 medical

research teams across NSW. The ACRF award widens the

collaboration even further to involve cancer research

teams throughout the nation.

The CFK is the brainchild of CMRI’s Professor Phil Robinson

and UoN’s Professor Adam McCluskey, whose teams have

worked together for over 10 years. CMRI Director Professor

Roger Reddel describes their long-standing partnership as

“extraordinarily dynamic and highly creative”.

Working in unison in the two purpose-built laboratories at

CMRI and UoN that will comprise the CFK, scientists will set

about understanding the Kinome - the subset of proteins

known as protein kinases.

Protein kinases are the master switches for all normal cell

functions. For this reason they are the target of many drugs

to treat human conditions. Humans have 518 protein kinases

and errors in kinases contribute to at least 400 different

diseases. These include cancer, neurological conditions,

cardiovascular diseases, inflammatory conditions, and asthma.

The combination of the expertise of the CMRI in proteomics

and UoN in medicinal chemistry in this exciting, world-

first venture opens the door to new ways to translate basic

research into new and improved therapies in many areas of

disease to benefit generations to come.

For Professors Robinson and McCluskey and their teams, and

CMRI Director Professor Roger Reddel, this fulfils a big dream.

Thanks to the foresight of the ACRF and the Ramaciotti

Foundations, and their willingness to support high risk

projects with high potential, we expect that the reality

will be even bigger.

PostscriptAs well as the prestigious award of the 2009 Major Initiative

for Biomedical Research Award, CMRI also received two

other Ramaciotti awards announced at the Awards Dinner on

November 12.

Dr Claus Hallwirth from

CMRI’s Gene Therapy

Unit received a $50,000

Biomedical Research

Establishment Grant, and

CMRI Director Roger Reddel

received a $50,000 grant

for the purchase of a new

ultracentrifuge to be used

in cancer, gene therapy and

epilepsy research.

Ramaciotti Award recipient, CMRI’s Dr Claus Hallwirth at the awards dinner

Architect’s drawing of the new building when complete