The current mission of our lab is to understand why the adult human beta cell – the cells that produce and secrete the hormone insulin – will not proliferate.
Why is this important?
Diabetes: Humans need insulin to store excess nutrients from food; if the production of insulin drops below a critical level, blood sugar levels rise, and if they persist, diabetes results. A reduction in insulin can result from exhaustion of the beta cell (Type 2 diabetes) or from beta cell death (Type 1 diabetes). Nearly 1/3 of all Canadians have diabetes or what is called prediabetes, elevated blood sugar that often continues to rise and result in a diabetes diagnosis; thus this is a national and indeed worldwide health concern.
Understanding the human beta cell: A promising strategy for treating diabetes is to simply replace non-functional or lost beta cells. This approach using intact human islets (the clusters of pancreatic cells that contain beta cells) has met with some success but does not last for more than five years, and there are not enough islets to treat all those affected. We are interested in exploring how we can get a patient’s own beta cells to proliferate and regenerate functional islets.
Regeneration: While several tissues possess the ability to regenerate, human beta cells appear to lose this capacity by the time we reach one year of age. We have identified two genes that are turned on in the human beta cell and which act as a brake on proliferation (Robitaille et al. 2016), and we have evidence that there are several more to be found. We specifically focus on the human beta cell, as there appear to be critical functional differences between the human beta cell and other species.
High throughput imaging screens: How do we do this? We use robot-enabled imaging to interrogate the human genome for novel genes that serve to slow down human beta cell proliferation. Once we have identified the genes involved, we can systematically characterize their biochemical function to permit the development of novel small molecules to promote beta cell proliferation in a controlled manner. We have also used this approach to identify genes that regulate the function and health of mitochondria, critical subcellular organelles that govern energy exchange and cell survival decisions (Lefebvre et al. 2013, Norton et al. 2014, Ng et al. 2014).
Personalized Medicine: In addition to diabetes, our work impacts on neurodegeneration and cancer. We have successfully adapted our screening protocols to permit screens in primary human cells, with a view to performing personalized functional screens for identification of genes that underlie patient-specific disease states.
Position available immediately for a Post-Doctoral Fellow. Project involves using functional genomics to identify novel regulators of human beta cell proliferation. Please submit your CV to Dr. Screaton by email roblab@gmail.com, and include a cover letter detailing your PhD work. Prior experience with cell culture of pancreatic beta cells, high-throughput image based screening, and molecular and cell biology is preferred. Outstanding candidates will be contacted for an interview.
Before sending an application, click here for advice! (from Delaney Lab, University of Victoria)