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BBSRC David Phillips Research Fellowship BBSRC David Phillips Research Fellowship an interdisciplinary perspective Dr. Ed Tate, Department of Chemistry,

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Presentation on theme: "BBSRC David Phillips Research Fellowship BBSRC David Phillips Research Fellowship an interdisciplinary perspective Dr. Ed Tate, Department of Chemistry,"— Presentation transcript:

1 BBSRC David Phillips Research Fellowship BBSRC David Phillips Research Fellowship an interdisciplinary perspective Dr. Ed Tate, Department of Chemistry, ICL Context: Current research Career Fellowship Applications: Personal perspective Hints and Tips Research fellowship: Advantages, challenges

2 Faculty of Medicine Fellowships Day July 2008 Dr. Ed Tate, Department of Chemistry BBSRC David Phillips Research Fellow (since 2006);

3 What is chemical proteomics? DNA RNAProtein TranscriptionTranslation Post-translational modification >300 types: Phosphorylation, glycosylation, lipidation, acetylation, proteolysis…

4 Origin Post-translational Modifications Phosphorylation Signalling Glycosylation Immune system Cell adhesion Prenylation Trafficking Acylation Membrane association Acetylation Transcriptional regulation Proteolysis Apoptotic cascade Ubiquitination Protein degradation SiteDynamics Function Chemical Proteomics Sulfenic acids Redox response

5 Site-specific labelling of proteins Metabolic tagging Target proteins tagged at site of PTM Protein bearing site- specific chemical feature (active site, PTM) Tagged PTM applied to cells/animal Proteins labelled site-specifically -+++ Drug mode-of- action studies ID proteins and site of PTM Live- and fixed- cell imaging Bioorthogonal ligation chemistry Chemical or enzymatic tagging

6 A platform for Chemical Myristomics (‘Azido-myristic’ acid) Secondary Labels Bioorthogonal ligation Secondary Labels MudPIT analysis 2D-DIGE On-bead purification

7 Activity-based probes Surface layer formation in C. difficile  C. difficile  Spore-forming anaerobe  Most lethal hospital superbug  Resistant to most antibiotics  Lack of genetic tools  Excretes a crystalline S-layer  Post-translational cleavage  Unknown cysteine protease Warhead Specificity element Linker Label Feed to C. difficileAffinity purify, ID

8 Future perspectives

9 Career Overview Career Overview PhD and Postdoctoral Work BSc in Chemistry (Durham) 1993 - 1996 PhD in Organic Chemistry (Cambridge) 1996 - 1999 1851 Research Fellowship (Ecole Polytechnique) 2000 - 2001 Howard Trust Research Fellowship (Institut Pasteur) 2002 - 2003 BBSRC-funded PDRA (ICL) 2004 - 2006 New C-glycosidation reactions Total synthesis of natural products Radical cyclisation chemistry Total synthesis of natural products Role of DNA helix stability & upstream sequences in transcriptional regulation Protein/peptide synthesis and engineering Library generation and screening techniques

10 Application Stage Situation as of August 2005  Prior Applications:  WT fellowship application in 2005 rejected – insufficient biochemical track record  Never been involved in writing a standard grant application!  Personal Situation:  Current PDRA contract due to expire 1 month after expected fellowship decision, no follow-on funding…  Baby due 22 nd November!  Research Track Record:  Good chemical research track record  No biochem research track record at time of application

11 Application Stage Plan of Action  Applied for multiple fellowships  EPSRC Advanced Research Fellowship (ARF)  BBSRC David Phillips Fellowship  Royal Society URF  Wellcome Trust  MRC  Novel proposal: chemical proteomics  Topical and interdisciplinary  Very limited literature precedent  Minimal preliminary data, and no prior track record!  Plan B: other grant proposals  Co-I on MRC Discipline-Hopping grant (related subject)  ‘Researcher Co-I’ on BBSRC responsive mode grant (different subject)

12 Application Stage Making Multiple Applications  Address Remit  Direct your proposal towards the funder’s remit  BBSRC: basic biology, complete independence (PI), 3-year postdoc  MRC: medical emphasis, strong training/career development component  Wellcome: technician for 5 years, previously had to have HoD as PI  EPSRC: steer clear of biological outputs (stick to technology only)  Royal Society: two FRS’s strongly supporting application, no support grant.  Remit is strictly based on the research outputs (‘deliverables’) of your project (not the methodology and techniques applied)  Be flexible, rewrite application to take account of funding available, in particular in justifying your costs  Advantages  Spreads the risk of hitting a referee with strong negative bias  Not always clear in advance of submission which funder is most appropriate

13 Application Stage Writing Applications  Writing the proposal  Steep learning curve, very time-consuming (2-3 months)  Sole PI, so responsible for all aspects of the proposal: financial, planning, scientific  Very good practice for later PI grant applications!  Costing the proposal  Costing may feel rather abstract on the application, but you will appreciate careful costing if you get the fellowship.  Acquire a working knowledge of Full Economic Costing (fEC)  The headline cost can be big: >£1 million for BBSRC DP Fellowship – but 30%+ goes direct to Faculty under fEC…  Request costs at the upper limit allowed if you can justify them for the proposed work.  You can usually move cash around later (within limits!)

14 Application Stage General Tips  Create a career narrative  Justify your career choices (in hindsight)  Highlight why you are ready to go independent  Fellowship proposals vs. grant proposals  An original, cutting-edge idea can carry more weight than a strong track record (esp. when compared to standard grants)  You can get away with having (much) less preliminary data  Interdisciplinary research may fare better in fellowship applications than in standard grant applications.  Salary level  Most funders don’t fix the level arbitrarily  You don’t usually need to justify your own salary level

15 Application Stage Writing Applications

16 Application Stage Stay or Go? Stay…  Access to existing equipment and collaborations  Minimal start-up time  Can you achieve independence? In either case… Ensure your expectations (support, space, teaching etc.) are understood by host institute Be prepared to justify choice of institute in the application and at interview Be prepared for questions regarding future independence if you decide to stay Or go?  Start afresh on your own terms  Will take time to get started May help to get out of the ‘golden triangle’…

17 Interview Stage Some suggestions  Presentation  Practise in front of a diverse audience  Keep it simple!  Interview  BBSRC interview is very brief (20min), and (relatively) friendly.  Interviews for other funders can be more intense…  Be prepared for questions on:  Past career choices  How will a fellowship benefit you and your research?  Minimal teaching, independence, opportunity to apply for further grants during fellowship.  How will you achieve independence?  Where do you see yourself in 5 years, 10 years…  Permanent position in academia, leader of a vibrant research group

18 Award Stage Challenges and Benefits  Benefits  Minimal teaching load (vs. lectureship)  = Time to set up collaborations, supervise research, write new grants…  Support from BBSRC  Once in post, be pro-active in applying for further funding:  From October: 14 (3 PDRAs, 9 PhD + 2 UG research students)  Over £1 million in PI research income (+ £1 million fellowship)  Challenges  Making the transition from PDRA to PI  Managing & applying for grants, recruitment  Supervising a group on your own  Dealing with internal departmental politics  You only have a few years to find a permanent position!   Start looking after 1-2 years  May entail a move to another institute  Consider whether fellows have routinely been taken on permanently at the host department/institute

19 Acknowledgements JemimaGillianTamTook PinarAlexLucy Postgraduate Students (PhD and MRes) WillSasala Postdoctoral Researchers JamesCamille Undergraduate Students

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