|Assistant Professor of MCD Biology
B. S., University of Alberta
M. S., University of Alberta
Ph.D., Cancer Research UK, Clare Hall Laboratories and University of London
Postdoctorate, University of California, San Francisco
The Ward lab is interested in how the remarkable complexity and noise of gene regulation is converted into the beautiful and precise cellular behaviors that drive animal development. Understanding how a genomic blueprint is read by transcription factors to control gene regulatory programs is challenging in animals due to the complexity of tissues and the often-long distances between transcription factor binding sites and regulated genes.
We use the nematode C. elegans as a model organism to approach this problem. In addition to its powerful genetics, simple tissues, transparency, and invariant cell lineage, C. elegans has an incredibly compact genome, which makes linking transcription factor binding to cognate gene regulation quite straightforward. We use a combination of genetics, molecular biology, microscopy, in vitro biochemistry, and genomics to determine how individual, evolutionarily conserved transcription factors regulate distinct gene expression programs controlling cell division and differentiation and organ development in living animals. We are especially interested in transcription factor regulation of two cellular processes: i) development of the nematode vulva, which is a paradigm of organogenesis; and ii) the nematode molt, which is the shedding of the old skin (cuticle) and generation of a new one. Molting is an essential process required for growth in any organism with an exoskeleton, and in nematodes involves a striking orchestration of asymmetric cell division, cell migrations and fusions, protease inhibition and release, signaling, extracellular matrix remodeling, and stereotyped behaviors.
We also extend our findings into the human parasitic nematode Brugia malayi, which causes the disfiguring disease lymphatic filariasis, in an effort to understand how the gene regulatory networks evolve in the context of a parasitic life cycle. We are also motivated by the public health implications of this work: parasitic nematodes infect over 1.5 billion people globally and also threaten food availability by infecting crops and livestock. As there are only a small number of drugs currently available to fight parasitic nematode infections (ie. lymphatic filariasis, ascariasis, strongyloidiasis), novel approaches are desperately needed. Molting is a particularly good target as it is essential, involves nematode-specific molecules, and is regulated by many druggable targets (proteases, nuclear hormone receptors, etc.). By characterizing key developmental processes in parasites, we aim to develop new approaches to combat helminthic infections.
Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.