Dr. Celia Greenwood Senior Investigator, Lady Davis Institute Professor, McGill University Montreal, QC, Canada
Two stories of genes, environment, and penalization
When exploring relationships between a trait (or a disease), one or more environmental factors, and a high dimensional genetic or genomic measure, we can make various assumptions about how to model and interpret the relationships. I will tell two stories: one where a simple model goes a long way to explaining the trait of interest, and another where a complex model is needed. In the first story, a lasso-penalized model built on genome-wide genotyping data enables good prediction of fracture and bone mineral density, and is completely uncorrelated with known lifestyle predictors of bone mineral density. In the second story, to model relationships between DNA methylation (measured via bisulfite sequencing) and phenotypes or covariates, we built a rich flexible model that allows for the effects, on the methylation levels, of multiple covariates to vary smoothly along small genomic regions. This method also allows for sequencing errors and can adjust for variability in cell type mixture. Here, penalization introduces smoothness for each covariate effect. We have started exploring associations between rheumatoid arthritis, cell type, and methylation with this new model.
Jyh-Yeuan (Eric) Lee, Ph.D. Professeur adjoint / Assistant Professor Biochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology Faculté de médecine / Faculty of Medicine, Université d’Ottawa / University of Ottawa
“More than just ABC”
The ATP-binding cassette (ABC) transporters carry out substrate translocation across cell membranes by coupling the energy of ATP binding and/or hydrolysis. While the ATPase domain is highly conserved, recent structural studies of ABC transporters have shown diverse structural folds in the integral transmembrane domains. Our research lies in mechanistic understanding of membrane cholesterol transport by studying the structure-function relationship of ABC transporters. This seminar presentation will includes the following three objectives. 1) I will give an overview of the structural diversity of ABC transporters. 2) Using ABCG5/G8 as the primary model, I will describe the challenge and the findings from studying ABC cholesterol transporters. 3) I will discuss our working model and future directions to investigate membrane cholesterol transport by ABC transporters.