Animals precisely control when and where genes are expressed; failure to do so can cause severe developmental defects and pathology. Transcription factors (TFs) must display extraordinary functional flexibility, controlling very different sets of genes in different cell and tissue types. To do so, they integrate information from signaling pathways, chromatin, and cofactors to ensure that the correct ensemble of genes is orchestrated in any given context. The number of regulatory inputs, and the complex physiology and large number of cell and tissue types in most experimentally tractable metazoans has rendered this combinatorial regulation of transcription nearly impenetrable. The compact genome, invariant development, simple tissues, and tools to track gene expression temporally and spatially make C. elegans an ideal model to study combinatorial transcriptional regulation in a developmental context. I am approaching this problem by exploring three distinct, yet related questions: i) how does a single input (sumoylation) regulate a single TF in different tissues and different points during development; ii) how do two TFs cooperate to integrate multiple inputs to control an essential, yet largely unexplored, developmental gene regulatory network (molting); iii) how has evolution shaped the molting gene regulatory network in a related nematode, the human parasite, B. malayi? Together these aims will dissect how complex regulatory inputs are integrated into gene regulatory networks temporally and spatially during development and how selective pressure during evolution shapes these networks.
My work using C. elegans to study parasitic nematode molting has been funded by a recently awarded K99 grant from the National Institute of General Medical Sciences. Writing a K99 was a challenging, ultimately rewarding experience. I have shared my K99 advice on the strategic planning that I undertook before writing the grant, as well as a list of resources that I found particularly helpful, in an article that I posted on my website: http://www.jordandward.com/k99-grant-writing.html
Ph.D., Biochemistry, 2004-2008
Clare Hall Laboratories, Cancer Research UK/University of London
Advisor: Prof. Simon Boulton
M.Sc. Microbiology, 2001-2004
University of Alberta
Advisor: Prof. Tracy Raivio
B.Sc. Honours (Microbiology), 1997-2001
University of Alberta/Red Deer College
Advisor: Prof. George Owttrim
Fellowships and Awards
2014-2016 NIGMS K99 award (K99GM107345)
2012 UCSF Resource Allocation Program grant
2012-2015 National Science Foundation grant (MCB-1157767; Yamamoto PI)
2011-2013 Canadian Institutes of Health Research Postdoctoral Fellowship (#113032)
2009-2011 Terry Fox Foundation Postdoctoral Fellowship (#700046)
Peer reviewed publications
(*denotes equal contribution, #denotes corresponding authorship)
1. Ward, J.D.# (2015) Rapid and Precise Engineering of the Caenorhabditis elegans Genome with Lethal Mutation Co-conversion and Inactivation of NHEJ Repair. Genetics 199(2):363-77
2. Ratnappan, R., F. Amrit, S.-W. Chen, H. Gill, K. Holden, J. Ward, K.R. Yamamoto, C.P. Olsen, and A. Ghazi. (2014) Germline Signals Deploy NHR-49 to Modulate Fatty-Acid β-Oxidation and Desaturation in Somatic Tissues of C. elegans. PLoS Genetics. 10(12):e1004829. doi: 10.1371/journal.pgen.1004829
3. Ward, J.D.#, K.R. Yamamoto, and M. Asahina. (2014) SUMO as a nuclear hormone receptor effector: New insights into combinatorial transcriptional regulation. Worm doi: 10.4161/worm.29317
4. Ward, J.D.#, B. Mullaney, B.J. Schiller, L.D. He, S.E. Petnic, C. Couillault, N. Pujol, T.U. Bernal, M.R. Van Gilst, K. Ashrafi, J.J. Ewbank, and K.R. Yamamoto. (2014) Defects in the C. elegans acyl‑CoA synthase, acs‑3, and nuclear hormone receptor, nhr‑25, cause sensitivity to distinct, but overlapping stresses.PLoS ONE. doi: 10.1371/journal.pone.0092552
5. Ward, J.D.*, N. Bojanala*, T.U. Bernal, K. Ashrafi, M. Asahina and K.R. Yamamoto. (2013) Sumoylated NHR-25/NR5A regulates cell fate during C. elegans vulval development. PLoS Genetics. 9(12), e1003992. doi: 10.1371/journal.pgen.1003992
6. Dickinson, D.J., J.D. Ward, D.J. Reiner, and B. Goldstein. (2013) Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination. Nat Methods. Oct;10(10):1028-34.
7. ONeil, N.J., J.S. Martin, J.L. Youds, J.D. Ward, M.I.R. Petalcorin, A.M. Rose, and S.J. Boulton. (2013) Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during C. elegans meiosis. PLoS Genet. Jul;9(7):e1003582. doi: 10.1371/journal.pgen.1003582.
8. Taubert, S., J.D. Ward, and K.R. Yamamoto. (2011) Nuclear hormone receptors in nematodes: Evolution and function. Mol Cell Endocrinol. 334(1-2): 49-55
9. Ward, J.D.*, D.M. Muzzini*, M.I. Petalcorin*, E. Martinez-Perez, J.S. Martin, P. Plevani, G. Cassata, F. Marini and S. J. Boulton. (2010) Overlapping Mechanisms Promote Postsynaptic RAD-51 Filament Disassembly during Meiotic Double-Strand Break Repair. Mol Cell 37(2): 259-272. (Article highlighted in Mol Cell (2010) 37(2):157-8*)
10. Youds, J. L., D.G. Mets, M.J. McIlwraith, J.S. Martin, J.D. Ward, N.J. O’Neil, A.M. Rose, S.C. West, B.J. Meyer and S.J. Boulton. (2010) RTEL-1 Enforces Meiotic Crossover Interference and Homeostasis. Science 327(5970): 1254-8.
11. Adamo, A., S.J. Collis, C.A. Adelman, N. Silva, Z. Horejsi, J.D. Ward, E. Martinez-Perez, S.J. Boulton and A. La Volpe. (2010) Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol Cell 39(1): 25-35.
12. MacRitchie, D.M., J.D. Ward, A.Z. Nevesinjac, and T.L. Raivio. (2008) Activation of the Cpx Envelope Stress Response Down-regulates Expression of Several LEE-encoded genes in Enteropathogenic Escherichia coli. Infection and Immunity. 76:1465-75
13. Barber, L.J., J.L. Youds, J.D. Ward, M.J. McIlwraith, N.J. O'Neil, M.I. Petalcorin, J.S. Martin, S.J. Collis, S.B. Cantor, M. Auclair, H. Tissenbaum, S.C. West, A.M. Rose, and S.J. Boulton. (2008) RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 135(2):261-71.
14. Adamo, A., P. Montemauri, N. Silva, J.D. Ward, S.J. Boulton, and A. LaVolpe. (2008) BRC-1 acts in the inter-sister pathway of meiotic double strand break repair EMBO Reports. 9: 287-292.
15. Youds, J.L., L.J. Barber, J.D. Ward, N.J. O'Neil, S.J. Collis, S.J. Boulton, and A.M. Rose. (2008) DOG-1 is the Caenorhabditis elegans BRIP1/FANCJ homolog and functions in interstrand cross-link repair. Molecular and Cellular Biology. 28:1470-9.
16. Goodyer, W., S. Kaitna, F. Couteau, J.D. Ward, S.J. Boulton, and M. Zetka. (2008) Distinct requirements for HTP-3 in the transition to a meiotic chromosome structure competent for DSB formation and homolog pairing In C. elegans. Developmental Cell. 14:263-74.
17. Hobson, N., N.L. Price, J.D. Ward, and T.L. Raivio. (2008) Generation of a restriction minus enteropathogenic Escherichia coli E2348/69 strain that is efficiently transformed with large, low copy plasmids. BMC Microbiol 8, 134.
18. Ward, J.D., L.J. Barber, M.I. Petalcorin, J. Yanowitz, and S.J. Boulton. (2007) Replication blocking lesions present a unique substrate for homologous recombination. EMBO Journal. 14: 3384-96
19. Collis, S.J., L.J. Barber, A.J. Clark, J.S. Martin, J.D. Ward, and S.J. Boulton. (2007) HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability. Nature Cell Biology. 4: 391-401
20. Collis, S.J., L.J. Barber, J.D. Ward, J.S. Martin, and S.J. Boulton. (2006) C. elegans FANCD2 responds to replication stress and functions in interstrand cross-link repair. DNA Repair. 11: 1398-406
Articles, blogs, other publications
1. Calarco, J. H. Chiu, D.J. Dickinson, A.E. Friedland, J. Lee, T.W. Lo, H. Schwartz#, Y. Tzur and J.D. Ward#. (2013) Workshop review: Engineered nucleases for genome editing in nematodes. Worm Breeder’s Gazette. 19(3): 26.
2. Ward, J.D. How to write a K99: One Canuck’s Perspective. http://www.jordandward.com/k99-grant-writing.html
3. Ward, J.D. An 'elegans' approach to better CRISPR/Cas9 editing efficiency. Invited blog, AddGene.org
Trail running, hiking, cooking, grilling/bbqing, good food and drink, watching football