Dr. Gian Luca Negri Genome Sciences Centre, BC Cancer Research Centre Unraveling biological complexity through proteomics: applications and challenges
Mass spectrometry has become a commonly used technique to study complex biological processes. Although several strategies now make it possible to measure the proteome with increasing depth and accuracy, several challenges remain. In this talk, I introduce the general workflow of mass spectrometry-based proteomics with a focusing on experimental design, technical and computational considerations. I use examples from flies to humans and highlight the intricacy of integrating mass spectrometry with other high-throughput data.
Dr. Ian Chin-Sang Department of Biology, Queen's University Using a tiny worm to help solve a big problem like cancer
Cancer often results when normal signal transduction pathways go awry due to the abnormal regulation or function of the genes in these pathways. A major oncogenic pathway is the Insulin and Insulin Growth Factor Signaling (IIS) pathway. The insulin and insulin-like growth factor signaling (IIS) pathways have multiple functions in development, metabolism, reproduction, lifespan and behaviour. A very important negative regulator of this pathway is the tumour suppressor PTEN. In a remarkable parallel, loss of the C. elegans PTEN orthologue (DAF-18) causes cells to divide when they should remain quiescent. Furthermore, the human PTEN can functionally replace worm DAF-18. When C. elegans hatch in the absence of food it shuts down its development until food is available in a process called L1 arrest. Normally during L1 arrest the Q neuroblasts remain quiescent, however, in daf-18 mutants the Q neuroblasts proliferate, migrate and differentiate. We have used genetic suppressor screens and pharmacological tests to identify novel branches and regulators of the C. elegans IIS. We also systematically overexpressed each of the 40 Insulin-like peptides in C. elegans to provide roles for each. We showed that some insulin peptides can activate the receptor while some inhibit the receptor, while others have mixed function (agonists or antagonists) depending on the developmental process. We have used this data to determine what makes an insulin-like peptide an activator or inhibitor of the DAF-2 insulin-like receptor. Our research using C. elegans has identified novel regulators of IIS and will help in the clinical setting by providing valuable information on human PTEN variants of unknown significance. The inhibitory insulin-like peptides will provide mechanistic insight for therapies to treat hyperinsulinemia related diseases.
Dr. Elizabeth Rideout Department of Cellular and Physiological Sciences, UBC Molecular mechanisms of sex-specific body size plasticity in Drosophila
The ability to adjust body size in response to nutrients differs between the sexes in most species, including mammals. Yet the molecular mechanisms underlying this sex-specific body size plasticity remain unknown. In our work, we used the fruit fly, Drosophila melanogaster, to reveal the molecular mechanisms underlying the sex difference in body size plasticity. Normally, the magnitude of the body size increase in response to a nutrient-rich diet is higher in female flies. We recently discovered that a nutrient-rich diet augments body size in females and not males because of a female-biased increase in activity of the conserved insulin signaling pathway. We further identified the factors that allow females, and not males, to augment insulin signaling in response to nutrients. This knowledge provides important evidence of how the insulin pathway can be regulated differently in each sex, and provides clues into why there are sex differences in so many phenotypes (e.g. lifespan) and diseases (e.g. type 2 diabetes) associated with the insulin pathway.