the university of edinburgh | the university of edinburgh ...bovine genome scientific highlights...

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ROSLIN Issue 14 W ell, after the post Xmas lull there seems to have been a rush of activity at The Roslin Institute. Our staff have been winning prizes and entry into top scientific societies, entertaining undergraduate students, fellow scientists, industry leaders and top Scottish Ministers, even doing silly things for charity. In amongst all this the science continues and we report in this issue some of the high profile publications that have come out from the Institute recently. Inside this issue: Events Director’s Message Scientific Highlights News in Brief Research Showcase Recent Publications Page 1 Page 2 Page 4 Page 5 Page 8 Page 10 Page 15 April 2009 reporter Steve Bishop Awarded 2009 BSAS Hammond Prize P rofessor Steve Bishop of The Roslin Institute has won the 2009 BSAS Sir John Hammond Prize. This is in recognition of his extensive contribution to research in animal science especially his novel work on the genetics of host variation in resistance to parasites and disease. This work has had a major influence world wide on how animal scientists and farmers approach breeding for nematode and infectious disease resistance. Recognising the limitations of drug control of helminth parasites particularly of sheep, Steve Bishop, in collaboration with University of Glasgow, initiated a programme to investigate the extent of variation in genetic resistance to such parasites. This revealed substantial amounts of variation, using faecal egg count as a marker, indicating that selection to increase resistance would be successful. Professor Bishop then developed novel genetic/epidemiological models to predict potential rates of improvement and revealed the important positive feedback in the system such that genetic improvement would reduce worm burden and pasture larval contamination as well as increase resistance. This work also revealed some of the mechanisms used by the host which lead to the genetic differences in resistance. The prize was presented at the BSAS Annual Meeting in Southport on 31 st March 2009 where Professor Bishop commented, “I am delighted to receive the prize in recognition of the work that teams of animal scientists at Roslin, SAC and the Universities of Glasgow and Edinburgh have undertaken. Great strides have been made in understanding the need and methods of selection for disease resistance, particularly worm resistance in sheep. This opens the door to identifying and selecting animals that can cope better with diseases in their environment with a minimum of drug related interventions. This is especially important in circumstances where drug resistance is an issue”. Steve Bishop is a New Zealander who took his undergraduate degree in Agricultural Science at Lincoln College, and subsequently a PhD in Genetics at the University of Edinburgh which he completed in 1985. Following a period at the Technical University of Munich at Weihenstephan and as a Geneticist at the Livestock Improvement Corporation in New Zealand, he returned to the UK in 1988 as a project leader at what is now The Roslin Institute, University of Edinburgh. There he has built up a major research group with an international reputation. Steve Bishop has made significant contributions in other areas of livestock genetics. This has included work on improvement of growth, meat quality and fatty acid composition in hill sheep, and specifically on individual loci contributing to variation in these and other species. He undertook studies with MLURI on cashmere goat breeding. He has undertaken a major joint with SAC, showing the lack of impact of selection for scrapie resistance markers on other production traits. BSAS President Professor Jamie Newbold and Professor Steve Bishop

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Page 1: The University of Edinburgh | The University of Edinburgh ...Bovine Genome Scientific Highlights Kirsty The genome sequence of taurine cattle: a window to ruminant biology & evolution

ROSLIN

Issue 14

Well, after the post Xmaslull there seems to

have been a rush of activityat The Roslin Institute. Our staff have been winningprizes and entry intotop scientific societies,entertaining undergraduatestudents, fellow scientists,industry leaders and topScottish Ministers, evendoing silly things for charity. In amongst all this thescience continues and wereport in this issue some ofthe high profile publicationsthat have come out from theInstitute recently.

Inside this issue:

Events

Director’s Message

Scientific Highlights

News in Brief

Research Showcase

Recent Publications

Page 1

Page 2

Page 4

Page 5

Page 8

Page 10

Page 15

April 2009

reporterSteve Bishop Awarded2009 BSAS Hammond Prize

Professor Steve Bishop of The RoslinInstitute has won the 2009 BSAS Sir

John Hammond Prize. This is inrecognition of his extensive contributionto research in animal science especiallyhis novel work on the genetics of hostvariation in resistance to parasites anddisease. This work has had a major influenceworld wide on how animal scientists andfarmers approach breeding fornematode and infectious diseaseresistance. Recognising the limitations of drugcontrol of helminth parasites particularlyof sheep, Steve Bishop, in collaborationwith University of Glasgow, initiated aprogramme to investigate the extent ofvariation in genetic resistance to suchparasites. This revealed substantialamounts of variation, using faecal eggcount as a marker, indicating thatselection to increase resistance wouldbe successful. Professor Bishop then developed novelgenetic/epidemiological models topredict potential rates of improvementand revealed the important positivefeedback in the system such that geneticimprovement would reduce worm burdenand pasture larval contamination as wellas increase resistance. This work alsorevealed some of the mechanisms used

by the host which lead to the geneticdifferences in resistance. The prize was presented at the BSASAnnual Meeting in Southport on 31st

March 2009 where Professor Bishopcommented, “I am delighted to receivethe prize in recognition of the work thatteams of animal scientists at Roslin, SACand the Universities of Glasgow andEdinburgh have undertaken. Greatstrides have been made inunderstanding the need and methods ofselection for disease resistance,particularly worm resistance in sheep.This opens the door to identifying andselecting animals that can cope betterwith diseases in their environment witha minimum of drug related interventions.This is especially important incircumstances where drug resistance isan issue”. Steve Bishop is a New Zealander whotook his undergraduate degree inAgricultural Science at Lincoln College,and subsequently a PhD in Genetics atthe University of Edinburgh which hecompleted in 1985. Following a periodat the Technical University of Munich atWeihenstephan and as a Geneticist atthe Livestock Improvement Corporationin New Zealand, he returned to the UKin 1988 as a project leader at what isnow The Roslin Institute, University ofEdinburgh. There he has built up a majorresearch group with an internationalreputation. Steve Bishop has made significantcontributions in other areas of livestockgenetics. This has included work onimprovement of growth, meat quality andfatty acid composition in hill sheep, andspecifically on individual loci contributingto variation in these and other species.He undertook studies with MLURI oncashmere goat breeding. He hasundertaken a major joint with SAC,showing the lack of impact of selectionfor scrapie resistance markers on otherproduction traits.

BSAS PresidentProfessor Jamie Newboldand Professor Steve Bishop

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Events

Page 2

This seminar programme is a key aspect of The Roslin Institute science programme. Are there arespeakers that you would like to hear and who will give a talk that will be accessible to and of interest

to most researchers within the broad spread of interests at The Roslin Institute? If there are, pleasesend the name of the speaker you would like to invite plus a few lines about why they will be aninteresting speaker to [email protected]. The suggestions will be reviewed by the seminarcommittee and if your suggestion is chosen you will be asked to host the speaker. If you want todiscuss your ideas with colleagues and possibly host as group etc. that is fine. PhD students andpostdocs are particularly encouraged to make suggestions. The timetable and administrative aspectsof the programme will be organised by Sheelagh Strachan.

Many seminars, workshops, conferences and other events are now listed on the new Roslin Institute website (http://www.roslin.ed.ac.uk/events/events.php).

Please check the site for updates and if you would like to have your event posted, please contact Tricia Hart([email protected]).

EBRC

SEM

INAR

SER

IES Helen

May 6th Dr Alison Gartland, University of Sheffield Medical School. “ATP: the

energy of life...and the skeleton”

13th Dr Lee Innes Moredun Research Institute. “Neospora caninum : a

significant cause of reproductive failure in cattle?”

20th Dr Erez Raz ZMBE University of Munster, Germany. “Primordial germ cell

migration in zebrafish”

27th Dr Uli Nuebel, Robert Koch Institüt, Germany. “Microevolution and

phylogeography of methicillin-resistant Staphylococcus aureus”

June 3rd Dr David Onions, Bioreliance. “Viruses, vaccines, pandemics and paranoia”

10th Professor Eleanor Riley, London School of Health and Tropical Medicine.“Regulation of immunity during murine and human malaria infections”

17th Dr Ross Fitzgerald, The Roslin Institute. “Host jumps, horizontal gene

transfer and the evolution of staphylococcal host-specificity”

24th Dr Keith Morris, MRC Human Reproductive Sciences Unit. “Advancements

in housing, husbandry and training in research”

All seminars take place at The Roslin Institute at 16:00-17:00.

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The next Edinburgh Mouse Club will take place atGeorge Square on 4th May 2009, 16:30-18:00. Further

information about the speakers and venue will be available nearerthe time athttp://www.roslin.ed.ac.uk/events/events.php

Edinburgh Mouse Club

The EBRC workshops are heldquarterly to focus on the work of

early career EBRC scientists (students,postdocs etc), and cultivate a valuableforum for discussion drawing speakersfrom Roslin, SAC, Moredun and the VetSchool. The aim is to fostercommunication and understanding ofeach other’s work in a friendly andinformal environment and develop linksbetween young researchers.

WORKSHOPS

The next EBRC workshop will will beadvertised nearer the time onThe Roslin Institute internet (http://www.roslin.ed.ac.uk/events/events.php).

Attendance is compulsory for allstudents and post docs. There will be sixpresentations with a coffee break halfway through. If you have any questionsplease contact your local representative(Roslin: Vicky MaCrae & Andy Green,SAC: Eileen Wall, Vet School: TimConnelley).

Andreas Lengeling, Bruce Whitelaw,Ian Jackson and I are proposing to

set up an informal Edinburgh MouseNewsletter to support the EdinburghMouse Club, which started in December2007. The aim is to help local scientists,with interests in research involving theuse of mouse models, exchange ideasand information and to foster newcollaborations for grant proposals etc.The Edinburgh Mouse Newsletter will becirculated as a pdf to everyone on theEdinburgh Mouse Club mailing list.

The plan is to keep the format simpleso we are asking you to send text to meas a Word or rtf document. Initially wewill aim for 4 issues per year, starting inMay, but we can increase the frequencyif it is successful.

There will be two main sections. The firstwill be contributed by principalinvestigators and will describe theactivities of their research group. The

second will be contributed by everyoneand will include items such as: StockExchange (if you need a stock or plan todiscard a stock), Scientific Meetings(send us details of relevant meetings),Seminars (send us details of localseminars that involve mouse research),Mouse services (e.g. cryopreservation,genotyping etc.) and Small Ads e.g.positions available, positions wanted,any interesting web sites you have foundthat deal with mice.

Note: I am using Word 2004 on anelderly eMac so if you are using a laterversion such as Word 2007 please saveit as an older version of Word or an rtfso I can open it.

Also please send me any other ideasand forward this email to anyone elsewho may be interested.

John West ([email protected])

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Well it’s been a busy old couple ofmonths. Communication has been

the key with a view to developing theinfrastructure and science of The RoslinInstitute.

In early March we were very pleased towelcome to the Institute Mr JohnSwinney, the Scottish Finance Minister.Joining him were Anne Glover (ChiefScientist for Scotland) and RhonaBrankin (local MSP) and along withInstitute colleagues and Sir Tim O’Shea(University Principal) we discussed themajor economic impact that animalsciences are having in Scotland now. Itwas a great opportunity for us todemonstrate to Mr Swinney how we atThe Roslin Institute and our colleaguesin the Easter Bush Research Consortium(EBRC) are driving forward the field onthe international stage. Of course suchan international presence requires state-of-the-art infrastructure to provide thesupport so I used the new computergenerated fly round of the new build(available at:

Directors Message

http:/ www.easterbush.estates.ed.ac.uk/)

Page 4

to garner support for the ongoing buildas well as the phase II plans. I think theRide of the Valkyries is appropriateaccompaniment.

April has provided a number ofopportunities to show off the science andthe scientists of the Institute. A verysuccessful Student Day provided us allwith a glimpse of the scientific stars ofthe future. This was followed by aResearch Showcase that demonstratedto representatives from around 50companies and other organisations thebreadth and quality of what The RoslinInstitute has to offer in the commercialsector. Several live leads came from this

day, and Sonja, Tricia and others did agreat job in organising it.

We also welcomed a number ofcolleagues from the University ofNottingham earlier this month.Nottingham vet school is, like our ownRoyal (Dick) School of VeterinaryStudies, a big RAE winner. There is alot of overlap between their research andours and we hope that there will be a lotof collaboration in the future; this meetingcertainly went a long way to getting therelationship onto a firm footing.

Food Security is very high up theBBSRC agenda, and I have been atseveral meetings in the past few weeksmoving towards a roadmap for futurefunding. Great to hear our BBSRC CEOpursuing this agenda publically in the lastweek, and I hope that in these DET(difficult economic times) we can stillpersuade the government to invest in thefuture.

Finally, I would like to end on a bumperset of congratulations. First to studentKatie Wu on winning the President’sprize for the best presentation at theWorld’s Poultry Science Association UKBranch annual meeting. Next toProfessor Steve Bishop on receiving theBSAS John Hammond award whichacknowledges the outstandingcontribution Steve has made to animalscience. And finally to Jean Manson onher deserved election as a fellow of theRoyal Society of Edinburgh. I have beensimilarly honoured this year by the RSE.We now have 6 Fellows in the Institute,a reflection of the esteem of our scienceand an opportunity to promote theInstitute and Scottish science in thefuture.

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Sequencing theBovine Genome

Scientific Highlights

Kirsty

The genome sequence of taurine cattle:a window to ruminant biology & evolution

ByKirstyJensen

Cattle are arguably the mostimportant mammalian livestock

species in the world. There areestimated to be over 1.3 billion cattleworld-wide; providing nutrition, draught-power and livelihood for the majority ofthe world’s population. Therefore, thecow was the obvious choice to be thefirst mammalian livestock species tohave its complete genome sequenced.The project was undertaken by theBovine Genome Sequencing andAnalysis Consortium and has involvedover 300 scientists from 25 countries.The culmination of this project, whichtook over five years and costed US$53mill ion, is the reporting of the 7xcoverage of the genome of an inbred,female Hereford cow named L1Dominette (Fig.1) in the journal Scienceon 24th April 2009.

The bovine genome is predicted to be2.87 Gbp in size and contains at least22,000 protein-encoding genes. Over4,000 of these predicted genes havebeen manually annotated, largely byvolunteers from the scientific community.

Over 400 genes were annotated duringthe Bovine Annotation Jamboree at TheWellcome Trust Sanger Centre, Hinxtonin May 2007, which was part funded byEADGENE. Several staff and studentsfrom The Roslin Institute and Royal(Dick) School of Veterinary Studiesattended the Jamboree (Fig. 2) and theirmain focus was the annotation ofimmune related genes, e.g. Toll-likereceptors, T cell receptor repertoire andMHC genes.

A companion article in Science reportson the investigation of genetic variationamongst cattle breeds. The completesequence of L1 Dominette andcomparative genome sequences of sixmore breeds was used to investigatesingle nucleotide polymorphisms innearly 500 cattle from 17 geographicallyand biologically diverse taurine andindicine cattle breeds. The resultsprovide further evidence that today’scattle breeds are derived from severaldomestication events.

The analysis of the bovine genomereported in these two Science papers,and 40 other companion papers that willbe published in a special issue of a BMCjournal, provide a unique insight into the

evolution of cattle. The cattle genomeis more similar to that of humans than isthe mouse genome and there is a highdegree of conservation in theirchromosomal architecture. Comparisonwith other genome sequences hasrevealed that the bovine genomecontains several duplicated segmentswhich affect genes important in cattlebiology, e.g. metabolism. This may helpto explain how cattle efficiently convertlow-quality food into energy-rich milk andmeat. It is hoped that this informationwill advance studies in cattle and leadto the selection of more productiveanimals. Overall, the bovine genomesequencing project has significantlyincreased our knowledge of cattlebiology and paves the way for newavenues of research.

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The immune response depends onthe swift detection of an invading

pathogen by innate immune cells. Theyrecognize the pathogens via binding ofvarious pattern recognition receptors toconserved pathogen associatedmolecules. The Toll-like receptors (TLRs)are a family of pattern recognitionreceptors that are an important linkbetween the innate and adaptiveimmunity. Many vaccines incorporateligands for TLRs as adjuvants toincrease protection against infectiousdiseases. These vaccines are normallydeveloped in rodent models, and theresulting data are then transferred toother species. But are they reallytransferable? This is one of the questionswe try to answer within a collaborativeproject of the bovine Toll-like receptorconsortium* which is coordinated byGenesis Faraday and financed byBBSRC and Pfizer.

In a recent paper we showed bycomparison of TLR2 gene phylogeny indifferent mammalian taxa that selective

Evolution of TLR structureand species-specificpathogen recognition By Liz Glass

and Oliver Jann

Figure: Distinct molecular surfaces (A, C) and electrostatic surface potential (B, D)

for the TLR-characteristic solenoid structure of the TLR2 ectodomain of human and

bovine TLR2. Black and white boxes indicate the region of the molecule evolving underadaptive selection. Within this area the ectodomains show clear differences in the structureas well as a highly divergent surface charge distribution (red indicating negative charges,blue indicating positive charges).

Liz

constraints differ between genera. Thesedifferences are particularly pronouncedat sites involved in ligand binding andheterodimerisation with other molecules.This suggests that adaptive selectionshapes ligand binding sites to improvethe recognition of different relevant,potentially host-specific pathogens.Whether the differences are based onstructural differences or differences insurface charge of the extracellulardomains, is yet to be discovered (Figure).

However, such differences are notlimited to TLR2 alone. There are alsoconsiderable differences betweenmammalian species in TLR4 mediatedrecognition of LPS from differentpathogens. Similarly, chicken TLR5possess different flagellin sensingqualities compared to human and mice,and single amino acid substitutions inbacterial flagellin can alter the species-specific TLR5 responses. Also a fewstudies have identified species-specificligands in a group of endosomal surfaceexpressed TLRs (TLR3, 7, 8 and 9).

* includes the RI Immunology group, theIAH Compton, the RVC London and theUniversity of Nottingham

Taken together it seems that TLR ligandrecognition and subsequent signallingcontains a species-specific component.In other words, there is a clear need toavoid extrapolation of results betweenspecies!

1. Jann OC, Werling D, Chang JS, HaigD, Glass EJ.: Molecular evolution ofbovine Toll-like receptor 2 suggestssubstitutions of functional relevance.BMC Evolutionary Biology 2008 Oct20;8:288.

2. Werling D, Jann OC, Offord V, GlassEJ, Coffey TJ: Variation matters: TLRstructure and species-specific pathogenrecognition. Trends in Immunology 2009,Mar;30(3):124-30.

References:

Oliver

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The hair follicle/skin relationship isrevealed by a twist in the tail

It is obvious that hair follicles areimportant for growing hair, but it has

long been known that follicles also helpto repair wounds by providing cells todamaged skin. This repair function iscritically important for mending largewounds, such as those caused by severeburns. However, whether hair folliclesever help the growth of unwounded skinhas been a subject of debate. Earlystudies indicated that during periods ofrapid body growth cells can emigratefrom hair follicles to the skin, while morerecent work suggests that this emigrationoccurs only upon wounding. For a number of years we have studiedhair follicle development using mutantmouse lines with impaired signallingthrough the EDA pathway. Theseanimals lack hair follicles and manyglands associated with the skin, havepoorly developed teeth and have kinkedtails (see Fig). As hair follicles, glandsand teeth develop in a similar mannerby budding off the embryonic skin itmade sense that they could all beinfluenced by the same mutation.However, the tail kinks have alwaysstood out as an unusual feature of themutant phenotype as these appeared tohave nothing to do with skindevelopment. Kinked tails are seen in many mutantand transgenic mouse lines and aretypically caused by abnormal bonedevelopment or incorrect folding of thetissue that becomes the spinal cord. Thissuggested that the EDA signallingpathway operates during bone or neuraltube development independently of itsaction in skin development. However,while studying hair follicle patterning wewere surprised to find that restoration ofEDA signalling specifically in the skin led

to straightening of the mutant tails, aswell as restoring hair foll icledevelopment. An undergraduate projectstudent, Jack Heath, analysed themutant and rescued lines and found thatthe mutants have vertebrae that becomecramped as the tail elongates. Inneonatal mutants the hairless skin failsto grow as quickly as the skeletonbeneath it, causing a pile up of vertebraeand the appearance of tail kinks.Stimulation of cell proliferation in themutant skin rescued the kinks,demonstrating that slow skin growth isthe primary cause of the kinking defect.We also tracked the emigration of veryrapidly cycling cells out of the folliclesand onto the skin and hypothesise thatthis cell population at the very top of thehair follicle is the one that contributes torapid skin growth. These findings show that even beforethey begin hair production the folliclesserve to pour cells out onto the skin tohelp it expand. This work adds to theemerging picture of hair follicles asmultifunctional organs with importantroles in producing and maintaining, aswell as insulating and decorating, ahealthy skin.

Wildtype

Mutant(Edaraddcr/cr)

Mutant with skin-specific rescue(Edaraddcrcr, Keratin14::Edaradd)

Denis

By Denis Headon

Page 7

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FRSE By Patricia Hart

News in Brief

Professor Hume has been the Directorof The Roslin Institute since 2007. He isan international authority in genomesciences, with a particular focus on thefunction of specialised cells of theimmune system in infection,inflammatory disease and cancer. Priorto taking his current post at The RoslinInstitute, Professor Hume was Directorof the ARC Special Centre forFunctionaand Applied Genomics at theInstitute for Molecular BioScience at theUniversity of Queensland.

Professor Manson is an internationallyrecognized scientist in TSE research.Her research focuses on elucidatingmechanisms of TSE diseasetransmission within and betweenindividuals using unique transgenicmouse models. She is a member of theWHO TSEs Working Group, the UKSEAC government advisory body andthe Executive Committee of theNeuroPrion EU Network of Excellence.She was awarded an OBE in the 2008New Year’s honour list.

The RSE was founded in 1783 by Royal Charter for the “Advancement of Learningand Useful Knowledge”. It is Scotland’s National Academy of Science and Letters.Today it has around 1500 Fellows whose expertise encompasses the full spectrumof the sciences, medicine, engineering and technology, education, law, the arts,humanities, social sciences, business, industry, the professions and public service.Its mission today is providing public benefit through the advancement of learningand useful knowledge.

Once admitted to the RSE Fellows are encouraged to contribute to the aims andobjectives of the Society, including the provision of expert policy advice to Governmentand Parliament, outreach education programmes for young people, and publicengagement events including conferences and discussion forums.

In welcoming the new Fellows, the RSE President, Lord Wilson of Tillyorn, said, “Iknow that the new intake of Fellows will enhance the already considerable knowledgebase of the RSE Fellowship. We will continue to put this expertise at the service ofeducation and policy development in Scotland, the UK, and where appropriateinternationally.”

Fellows of the Royal Society of Edinburgh (RSE), Professor Alan Archibald andSir John Savill (Vice Principal and Head of College) offered their congratulations

to Professor David Hume (Director of The Roslin Institute) and Professor Jean Manson(Head of the Institute’s Neuropathogenesis Division) on their election as fellows tothe RSE.

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Student Day By Patricia Hart

The annual Royal (Dick) School ofVeterinary Studies (R(D)SVS)

Research Student Day event was heldat the Easter Bush Veterinary Centre onWednesday 1st April 2009. This wasorganised for the first time in cooperationwith The Roslin Institute, which becamea part of the R(D)SVS in May 2008 andit led to an increased level of diversity ofpresentations.

Bernadette Dutia (the PostgraduateCoordinator) welcomed everyone andintroduced the event before HebaAhmed Abd-Alla had the unenviable jobof making the first presentation. All thefinal year students were giving oralpresentations of their research and thespeakers were of a very high standard.They spoke with confidence andpresented their work very well. As finalyears they are clearly ready to move onand take the research world by storm.

The R(D)SVS was identified as the topUK vet school for research in the 2008Research Assessment Exercise and itwas not difficult to see why. The school’sresearch spans an exciting array ofsubjects from assessing host-pathogeninteractions across a broad spectrum ofinfectious diseases, to cancer research,

neuroscience, genomic analysis ofdisease and epidemiology amongstother subject areas.

Professor David Hume, Director ofResearch at the R(D)SVS sent hiscongratulations to all the post graduatestudents who took part in Student Day.He noted that the oral and posterpresentations were of such a highstandard that the judges had found itvery difficult to decide who would receivethe prizes. Professor Hume said, “Wehave some really excellent students atThe Roslin Institute and R(D)SVSworking on a very diverse group ofsubjects and it was good to see that soably demonstrated at the Student Day”.

The day was concluded by a keynotelecture. This year the R(D)SVS waspleased to welcome Professor Jim Neilof the Leukaemia Research Fund/Cancer Research UK MolecularOncology Laboratory, University ofGlasgow as he presented his lecture“Retroviruses and cancer genomics:past, present and future.” ProfessorDavid Argyle introduced Professor Neilwho is an internationally respectedvirologist and his work has increasedwhat is known about retroviruses

causing cancer which has in turnimproved the knowledge of mechanismsin cancer.

Professor Neil’s talk described theprocess by which he has identified anumber of genes involved in cancer. Anumber of cellular oncogenes areactivated by retroviral insertion in atissue specific manner and it is bystudying these integration events thatProfessor Neil has identified a numberof oncogenes. He also discussed thesafety of retroviral vectors and genetherapy towards the end of what was anextremely interesting and informativepresentation.

At an evening wine reception thewinners of the poster and oralpresentation prizes amounting to £1,000were announced. They were:First year studentposter prize: Katherine StainesSecond year studentposter prize: Laura BaileyMVetSci/Msc by Research studentposter prize: Bryony WaggettFinal year oral presentationfirst prize: Jennifer GillFinal year oral presentationsecond prize: Wandee Kongkaew

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Research Showcase atThe Roslin Institute and R(D)SVS By Patricia Hart and Sonja Vujovic

Research from The Roslin Instituteand the Royal (Dick) School of

Veterinary Studies (R(D)SVS) at theUniversity of Edinburgh was showcasedat an event to foster relationshipsbetween academia and industry.

Researchers provided presentations onprojects at The Roslin Institute andR(D)SVS. These included researchassessing potential applications of stemcells from livestock and companionanimals, generation of appropriatemodels of disease to refine therapeuticstrategies and studies looking at howgenetic variation in production animalscan be exploited by breeding forimproved disease resistance.

Professor Anne Glover, Chief ScientificAdviser for Scotland, who spoke at theevent said, “Scotland has an enviablerecord in terms of the quality of itsresearch. Now, more than ever, it is vitalthat research is partnered with businessacumen through industry collaborations.This will help ensure that the high qualitytranslatable research carried out at TheRoslin Institute and the Royal (Dick)School of Veterinary Science fulfils its

potential to impact on and improvehealth, both in Scotland andinternationally.”

Representatives from 50 companiesand other organisations such as PfizerLtd, Novartis Animal Health, Aviagen Ltd,Scottish Enterprise and MidlothianCouncil attended the event aimed atpromoting collaboration andpartnerships.

Dr Tom Shepherd, Chief ExecutiveOfficer of CXR, is an existing industrialpartner working with The Roslin Institute.He spoke about how the collaborationhas been using state of the art transgenictechnologies to develop new tools toassess the safety of drugs andchemicals. He said: “The Roslin Institutehas an enviable position in the field ofanimal biotechnology and through itsrestructuring now has the opportunity tobuild on this and be a significant playerin the animal bioscience sector.”

The Royal (Dick) School of VeterinaryStudies, which was ranked as theleading vet school in the UK’s 2008Research Assessment Exercise with the

highest proportion of world leadingresearch, will also benefit from a new£42 million teaching building sited nextto the Hospital for Small Animals.

This event was deemed to be a greatsuccess by those who attended it and anumber of important new contacts weremade between the Roslin and R(D)SVSscientists and their guests from industryand elsewhere.

Professor David Hume, Director of TheRoslin Institute and Research Directorof Research at R(D)SVS, said:“Research at The Roslin Institute andR(D)SVS aims to enhance the lives ofanimals and humans through improvedhealth and welfare. In order for us tohave the best chance of applying ourresearch outputs to achieve our aims, itis critical that we work closely withindustry and this event has been anexciting step forward in that process.”

Further images are available at:

(www.roslin.ed.ac.uk/industry-day/gallery/)

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Roslin Student wins WPSA UK prize By Paul Hocking

Katie Wu, a former Roslin Instituteproject student, was awarded the

President’s prize for the bestpresentation at the World’s PoultryScience Association UK Branch annualmeeting on March 30-April 1st atSouthport, UK. Katie took an intercalatedMSc in Animal Behaviour and Welfareat the Royal (Dick) School of VeterinaryStudies (R(D)SVS) last year and did herproject with Paul Hocking at the Institutein the summer of 2008. She is now a thirdyear vet student at Edinburgh.

Her project (which was funded througha WPSA UK Branch summer scholarshipand BBSRC funding) was entitled“Effects of age of bird and litter moisturecontent on foot pad dermatitis inturkeys”. Poor litter management hasbeen the main contributing factor ininducing foot-pad dermatitis (FPD) andother dermatological problems in

commercial turkey farms. FPD causeseconomic losses through downgradingand carcass condemnations and resultsin welfare concerns. High litter moistureconcentration can induce FPD and in thefirst of two experiments the relationshipbetween the proportion of water in thelitter and the severity of FPD lesions wasquantified. The objective of the secondexperiment was to determine therelationship between age and thepropensity to develop FPD.

The results confirmed the importance oflitter moisture in causing FPD andshowed that turkeys from hatch to 10weeks of age can be affected. Wet littermay cause more feed to be consumedbecause of the energy costs ofevaporation and conduction from wetbody surfaces whereas lower activitymay conserve energy.

Workshop Identifies NewCollaborative OpportunitiesLiz Glass (Roslin) and Gary Entrican

(Moredun/UoE) organised a jointRoslin/Moredun workshop on“Identification of new collaborativeopportunities for research into diseasescaused by intracellular pathogens” heldon 13 March 2009 at Moredun. Thisworkshop brought together a number ofMoredun and Roslin researchers toexplore areas of common interest andcomplementary skills in this area.

The meeting kicked off with a round-table introduction of the participants (LizGlass, Gary Entrican, David Hume, JohnFazakerley, Bob Dalziel, Colin McInnes,David Griffiths, Karen Stevenson, DavidGE Smith, Neil Mabbott, FrancescaChianini, Julio Benevides and Tahar Ait-Ali) followed by a series of short talkscovering a wide range of host species(cattle, sheep and pigs) and theirinteractions with intracellular pathogens,including bacteria and viruses. Garyopened this session with a talk on theimmunological resources available forthese species under the BBSRC funded

“Immunological Toolbox” (http://www.immunologicaltoolbox.com/) andhe briefly mentioned a new funding bidthat is being prepared to continue thisresource. He went on describe the workon Chlamydophila abortus, the mostcommon diagnosed cause of infectiousabortion in sheep flocks in the UK.

Liz described some of the patternrecognition receptors involved in sensingintracellular pathogens, focusing on hergroup’s latest research on positivelyselected single nucleotidepolymorphisms in toll-like receptors andtheir association with variation in immuneresponse and disease resistance.

David Hume gave a very interesting talkon the discovery of a viral PRR thatsenses the presence of double strandedDNA in the cytosol (see http://www.roslin.ed.ac.uk/news/news.php/10017) and which is highly expressed inmacrophages. These cells essentiallydrop dead if this receptor is switched on,making it impossible to transfect primarymacrophages unless a siRNA transcriptfor this receptor is co-transfected. Itseems likely that more PRRs forintracellular pathogens are waiting to bediscovered.

Next up was John Fazakerley whodescribed how insect cells utilise theRNA-induced silencing complex (RISC)as an antiviral defence mechanism totarget RNA viruses such as SemlikiForest Virus for destruction. Intriguingly,however, not all regions of the viralgenome are targeted.

Other talks were from Colin McInneswho gave a general overview of theprincipal livestock diseases worked on

with the Moredun Virology Division (orf,ovine pulmonary adenomatosis andmalignant catarrhal fever), Bob Dalzielwho described his rat model for post-herpetic pain and how this can be usedto screen for effective drugs to controlpain relief in e.g. shingles in humans andDavid GE Smith discussed hisproteomics approach to teasing out howthe very common obligate intracellularpathogen, Lawsonia intracellularis,invades and induces proliferation of gutepithelial cells in pigs. Last and by nomeans least, Neil Mabbott gave afascinating talk on the role of folliculardendritic cells in accumulating PrP fromthe gut, and their importance in theresulting infection of the brain.

The workshop went on longer thanplanned but it was felt to have been veryworthwhile and there was enthusiasm tohold a follow-up workshop towards theend of the year.

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NPD ThanksThe Neuropathogenesis Division

would like to thank everyone atRoslin for all their warm welcome, helpand support during their move fromKings Buildings to Roslin. The move hasinvolved a great deal of work across theDivision, but Jean Manson and hercolleagues are mindful of the fact that alot of other Roslin colleagues have spenta massive amount of time ensuringeverything went smoothly. Thank you toall those who were directly involved, butthanks also to all the helpful souls whohave given directions and advice to lostlooking Neuropathogenesis Division stafffound aimlessly wandering corridors andchicken huts! We look forward to workingmore closely with you in the years to come.

Undergraduate Visitors By DJ de Koning

On Thursday 16th of April the Institutehosted a visit by 60 third year

students in Animals Sciences fromWageningen University. After a 3 hourbus trip from Newcastle they were veryhappy to use the Institute facilities andbe welcomed with coffee and pastries.During the rest of the morning thestudents were entertained by apresentation from Aviagen. After anextensive lunch they were introduced tothe Institute by David Hume, followed byshort & sharp research talks by RossHouston, Kirsty Jensen and WilfredGoldmann. After more coffee & biscuitsthey were bussed to the farm where TimKing, John Bracken and Bruce Whitelawprovided a very informative farm tour.The green pigs and Sahiwal cattle werefirm favourites for photo opportunities.The speakers were all provided withorange towels to commemorate the visit.The visit went extremely smoothly thanksto help of many, including Liz Brown,Patricia Hart, Suzanne Rowe, BurakKaracoeren, Javad Nadaf, Bruno Louroand Eva Strucken. The students werevery interested and uncharacteristicallywell behaved. Still, just as well the glasssheep did not arrive earlier….

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Page 13: The University of Edinburgh | The University of Edinburgh ...Bovine Genome Scientific Highlights Kirsty The genome sequence of taurine cattle: a window to ruminant biology & evolution

David Hume Presents His Inaugural LectureOn 17th March 2009 Professor David

Hume, Director of The RoslinInstitute and Research Director, Royal(Dick) School of Veterinary Studies,presented his Inaugural Lecture in frontof an audience of invited guests.

The Principal of the University ofEdinburgh, Professor Sir Tim O’Shea,introduced David providing his biographyand the international route David hastaken on his journey to his currentposting at The Roslin Institute.

David started his lecture by noting thathe had actually dreamed of becoming aworld class footballer, but a number ofinspiring scientific mentors managed toturn his gaze from the football field tothe laboratory. Over time David’sinterests were fixed on macrophagebiology and so we came to the main partof his lecture “Macrophages, theUniverse and Everything”. Daviddescribed what macrophages are andset to impress upon his audience howimportant they are, at one pointchallenging them to name a disease thatdoes not involve macrophages in someway (I’m sure the challenge still standsif you can name such a disease). Davidalso described how he has used

genomics in his research and laid out hisfuture aspirations.

The new Professor of MammalianFunctional Genomics finished hisinaugural lecture by highlighting what anexciting time this is in his career as wellas that of The Roslin Institute andthanked his various colleagues over the

years for their involvement and supportduring his career so far.

Professor Sir Tim O’ Shea concludedthe occasion with his vote of thanks, thenthe evening was rounded off with a winereception to celebrate Professor Hume’sprofessorship.

By Patricia Hart

John Swinney Visit By Patricia Hart

The Roslin Institute was delighted towelcome the Scottish Government’s

Finance Minister, Mr John Swinney MSP.Mr Swinney was visiting to hear aboutthe work of The Roslin Institute and how

new state of the art large animal facilitiesand further research facilities. Alsoattending were Professor Anne Glover,the Chief Scientific Advisor for Scotland,representatives from Scottish Enterprise,Sir Tim O’Shea (University of EdinburghPrincipal) and Sir John Savill (Head ofthe College of Medicine and VeterinaryMedicine. Prof Hume said, “It was apleasure to welcome Mr Swinney to TheRoslin Institute and we had what I hopewill turn out to be a very productivediscussion about the possibilities to putScottish Animal Sciences at the forefrontof the world stage.”

it fits with the overall area of animalbioscience across Scotland. Scotlandhas a very strong base of animalbioscience research which puts it at theforefront of the field internationally. TheInstitute’s Director, Prof David Hume,was keen that Mr Swinney should beaware of the powerful position Scotlandis in and identified Animal Bioscience asa key area in Scottish science that wouldbenefit greatly if the ScottishGovernment provided its support. ProfHume noted the ongoing infrastructuredevelopment at the Institute andhighlighted the future plans for phase IIfunding that will provide capacity to build

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There were two main reason Inominated my legs to become as

smooth as a babies bum. The first andmost obvious, was to raise as muchmoney for Red Nose Day as possible,the second was because I thought itwould give everybody in the Institute agood giggle.

Rumours have it that a woman’s painthreshold is higher than a man’s andtherefore I expected the waxingexperience to scar me, both mentally andphysically, for life. What a bunch ofrubbish. It was indeed painful but it wasnowhere near as bad as all the ladiesmade out. That doesn’t mean to say thatI will be doing it again anytime soonhowever!

My legs currently look like the outcomeof a crossbreeding experiment betweena teenagers bum fluff and a BernardMathews chicken drum stick. It is safeto say that I will not be donning a pair ofshorts anytime soon.

I raised a total of £350; this total includedthe quiet efforts of my fellow colleagueRona Wilson. Unbeknown to anyoneoutside of the cult that is the NPD, Ronajogged a gruelling 6 miles from her house(close to Mayfield Road) to the Institutein under an hour. Despite feeling a bit

Roslin doing “Something Funny for Money” By Iain Kennedyand Rona Wilson

anxious beforehand, she told me thatonce she got going she was determined

Nottingham Visit By Patricia Hart

The Roslin Institute is always keen toarrange new collaborative

opportunities so it was with greatpleasure that a group of Roslin researchleaders welcomed to the Institute six oftheir counterparts from the University ofNottingham: Prof Paul Barrow, Prof PhilGarnsworthy, Prof David Haig, DrRichard Lea, Dr Tim Parr and Dr KevinSinclair. The guests represented theSchool of Veterinary Medicine andScience and the School of BiologicalSciences and the research taking placewithin the two schools was introducedby Prof Haig. In turn The Roslin Instituteresearch leaders introduced theirresearch and the numerous areas ofoverlap were immediately obvious. Stemcell biology, genetic modification ofalternative species for modelling humandiseases, reproductive biology, foodsafety, TSEs, host/pathogen interactionsand epidemiology were all among themany subjects noted as being on thescience strategy for both organisations.

A number of links already exist betweenThe Roslin Institute and the University

of Nottingham; David Haig collaborateswith Liz Glass studying toll like receptorsin cattle and sheep and Bruce Whitelawretains links with Prof Keith Campbellwho previously worked at the Instituteand was a key member of the groupwhose research led to Dolly the Sheep.Additionally John Woolliams and SteveBishop hold professorial positions at theUniversity of Nottingham, School ofBioscience.

Towards the end of the afternoon anumber of different opportunities wereidentified for future interaction andmechanisms for continuing exchange ofideas were proposed so hopefully this isthe start of a long and successfulassociation between two of the leadingplayers in UK Animal Science.

not to stop. While a good part of herjourney was uphill, she had the weatheron her side and leaving so early meantshe avoided the distraction of the traffic.In the end she actually surprised herselfby making it to work in less than an hourand now she’s planning to run a 10K atthe beginning of May.

I would like to thank everybody for theirkind generosity.

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Recent Roslin Institute Publications

Page 15

If you have any articles you would like to submit for the next Roslin Reporter, please contact:Patricia Hart, Scientific Administrator (email:[email protected] or phone: 0131 527 4200)

or require imagery to accompany articles, please contact:Design and Print Department, Roslin Institute (email:[email protected] or phone: 0131 527 4327/4356)

Ait-Ali T, Wilson AW, Finlayson H, CarréW, Chakravarthy Ramaiahgari S,Westcott DG, Waterfall M, FrossardJP, Baek KH, Drew TW, Bishop SC,Archibald AL. 2009. Functional analysisof the porcine USP18 and its role duringporcine arterivirus replication. Gene.Mar 10. [Epub ahead of print]

Alvarez R, Hocking PM. 2009.

Stochastic modelling of optimum initial

body weight, daily weight gain and

effect of genetic changes in ovulation

rate and age at sexual maturity on total

egg production of broiler breeders. Br

Poult Sci. 50(1):135-43.

Alvarez R, Hocking PM. 2009.Successful modification of a stochasticmodel of egg production in broilerbreeders housed in temperate climatesto predict flock productivity in tropicalfarms in Venezuela. Br Poult Sci.50(1):131-4.

Ambo M, Moura AS, Ledur MC, Pinto

LF, Baron EE, Ruy DC, Nones K,

Campos RL, Boschiero C, Burt DW,

Coutinho LL. 2009. Quantitative trait

loci for performance traits in a broiler x

layer cross. Anim Genet. Jan 20. [Epub

ahead of print]

Attarzadeh-Yazdi G, Fragkoudis R, ChiY, Siu RW, Ulper L, Barry G, Rodriguez-Andres J, Nash AA, Bouloy M, MeritsA, Fazakerley JK, Kohl A. 2009. Cell tocell spread of the RNAi responsesuppresses Semliki Forest virusinfection of mosquito cell cultures andcannot be antagonised by this virus. JVirol. Mar 18. [Epub ahead of print]

Bell-Sakyi L, Ro~ek D, Gould EA. 2009.

Cell lines from the soft tick Ornithodoros

moubata. Exp Appl Acarol. Mar 1.

[Epub ahead of print]

Dunn IC, Wilson PW, Lu Z, Bain MM,

Crossan CL, Talbot RT, Waddington D.

2009. New hypotheses on the function

of the avian shell gland derived from

microarray analysis comparing tissue

from juvenile and sexually mature hens.

Gen Comp Endocrinol. Mar 20. [Epub

ahead of print]

The FANTOM Consortium and theRiken Omics Science Center. 2009.The transcriptional network thatcontrols growth arrest anddifferentiation in a human myeloid

leukemia cell line. Nat. Genet. 19 Aprildoi:10.1038/ng.368 [Epub ahead of print]

Faulkner GJ, Y Kimura, CO Daub, SWani, C Plessy, KM Irvine, K Schroder,N Cloonan, AL Steptoe, T Lassmann,K Waki, N Hornig, T Arakawa, HTakahashi, J Kawai, ARR Forrest, HSuzuki, Y Hayashizaki, DA Hume, VOrlando, SM Grimmond & P Carninci.2009. The regulated retrotransposontranscriptome of mammalian cells. Nat.Genet. 19 April doi:10.1038/ng.368[Epub ahead of print]

Headon DJ. 2009. Ectodysplasin

signaling in cutaneous appendage

development: dose, duration, and diversity.

J Invest Dermatol. 129(4):817-9.

Hughes K, C, Chudek JA, Goodyear

SR, Aspden RM, Talbot R, Gundersen

TE, Blomhoff R, Henderson C, Wolf

CR, Tickle C. 2009. Cholesterol

metabolism: The main pathway acting

downstream of cytochrome P450

oxidoreductase in skeletal development

of the limb. Mol Cell Biol. Mar 9. [Epub

ahead of print]

Jensen K, Makins GD, Kaliszewska A,

Hulme MJ, Paxton E, Glass EJ. 2009.

The protozoan parasite Theileria

annulata alters the differentiation state

of the infected macrophage and

suppresses musculoaponeurotic

fibrosarcoma oncogene (MAF)

transcription factors. Int J Parasitol. Mar

19. [Epub ahead of print].

Lam AC, Powell J, Wei WH, de Koning

DJ, Haley CS. 2009. A combined

strategy for quantitative trait loci

detection by genome-wide association.

BMC Proc. 3 Suppl 1:S6.

Mellanby RJ, Thomas DC, Lamb J.

2009. Role of regulatory T-cells in

autoimmunity. Clin Sci (Lond).

116(8):639-49.

Nieuwhof GJ, Conington J, BishopSC.2009. A genetic epidemiologicalmodel to describe resistance to anendemic bacterial disease in livestock:application to footrot in sheep. GenetSel Evol. 41(1):19.

Pang LY, Argyle DJ. 2009. Using

naturally occurring tumours in dogs and

cats to study telomerase and cancer

stem cell biology. Biochim Biophys

Acta. Feb 28. [Epub ahead of print]

Pass C, MacRae VE, Ahmed SF,

Farquharson C. 2009. Inflammatory

cytokines and the GH/IGF-I axis: novel

actions on bone growth. Cell Biochem

Funct. 27(3):119-27.

Quan M, Murphy CM, Zhang Z, Durand

S, Esteves I, Doel C, Alexandersen S.

2009. Influence of Exposure Intensity

on the Efficiency and Speed of

Transmission of Foot-and-Mouth

Disease. J Comp Pathol. Feb 10. [Epub

ahead of print]

Rowe SJ, Pong-Wong R, Haley CS,

Knott SA, De Koning DJ. 2009.

Detecting parent of origin and dominant

QTL in a two-generation commercial

poultry pedigree using variance

component methodology. Genet Sel

Evol. 41(1):6.

Sandercock DA, Nute GR, Hocking PM.

2009. Quantifying the effects of genetic

selection and genetic variation for body

size, carcass composition, and meat

quality in the domestic fowl (Gallus

domesticus).Poult Sci. 88(5):923-31.

Sandercock DA, Barker ZE, Mitchell

MA, Hocking PM. 2009. Changes in

muscle cell cation regulation and meat

quality traits are associated with genetic

selection for high body weight and meat

yield in broiler chickens.Schmidt

Taft RJ, EA Glazov, N Cloonan, CSimons, S Stephen, GJ Faulkner, TLassmann, ARR Forrest, SMGrimmond, K Schroder, K Irvine, TArakawa, M Nakamura, A Kubosaki, KHayashida, C Kawazu, M Murata, HNishiyori, S Fukuda, J Kawai, CO Daub,DA Hume, H Suzuki, V Orlando, PCarninci, Y Hayashizaki & JS Mattick.2009. Tiny RNAs associated withtranscription start sites in animals. Nat.Genet. 19 April doi:10.1038/ng.368[Epub ahead of print].

Yin Y, Bangs F, Paton IR, Prescott A,

James J, Davey MG, Whitley P,

Genikhovich G, Technau U, Burt DW,

Tickle C. 2009. The Talpid3 gene

(KIAA0586) encodes a centrosomal

protein that is essential for primary cilia

formation. Development. 36(4):655-64.

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