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 include 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.
Professor Department of Microbiology & Immunology Geisel School of Medicine at Dartmouth Hanover, NH
To Build a Biofilm
Biofilms are surface-attached microbial communities. c-di-GMP is a conserved dinucleotide signal that regulates biofilm formation by bacteria. In Pseudomonas fluorescens, a critical pathway for biofilm formation requires the localization of a larger cell surface adhesion, called LapA, to the cell surface. Localization of LapA is regulated by the dinucleotide signaling molecule c-di-GMP. Synthesis of c-di-GMP by diguanylate cyclases (DGCs) and its degradation by phosphodiesterases (PDEs) is well established, and progress has also been made in elucidating c-di-GMP output systems. For example, our group has characterized a membrane protein, LapD, which binds c-di-GMP via a degenerate PDE domain; this c-di-GMP receptor regulates localization of the LapA adhesin to the cell surface, which is a critical event for biofilm formation by P. fluorescens. A central open question in the field is how bacteria like P. fluorescens and P. aeruginosa, with 50+ proteins that make, break and bind c-di-GMP, coordinate the action of these many proteins to provide a coordinated, c-di-GMP-regulated output. I will discuss two aspects of recent work from the lab: (i) explore mechanisms of c-di-GMP signaling specificity that impact the control of a biofilm adhesin system that is conserved in 500+ bacterial genomes, (ii) describe recent findings demonstrating a novel mechanism whereby the c-di-GMP-regulated adhesin LapA is localized to the surface.