BMBDG Seminar - Jennifer Mitchell

“Comparative epigenomics determines transcriptional regulatory codes in mammalian genomes,” by Jennifer Mitchell, Department of Cell and Systems Biology, University of Toronto.

Abstract: Non-coding transcriptional enhancers are critical for development, phenotype divergence during evolution and often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown. Enhancers are key drivers of pluripotency maintenance and the reprogramming process; therefore, determining the repertoire of sequences and transcription factors that confer activity to these regions will provide a better understanding of the pluripotent state and reveal transcriptional control mechanisms that define cell identity. Attempts to construct synthetic enhancers using the binding sequences for known pluripotency master regulators reveal our knowledge gaps, as these sequences display activity that is 10 fold lower than an endogenous native enhancer. We used comparative epigenomics to identify conserved enhancers in naïve mouse and human embryonic stem cells. Machine learning revealed these conserved enhancers are enriched in a conserved repertoire of 70 different transcription factor binding sites (TFBS) including known and novel pluripotency regulators. Remarkably, using a diverse set of >10 TFBS from this repertoire was sufficient to construct short synthetic enhancers with activity comparable to native enhancers. We next used this approach to predict the TFBS repertoire for different lineage committed cells and identified embryonic enhancers conserved between mouse and human. These developmental enhancers are normally silenced in the adult but become reactivated in adult cancers.

Monday, December 7, 2020 at 2:30 pm. Join by Zoom.

Hosted by Dr. LeAnn Howe

“New modalities for interfering with outer membrane biogenesis in Gram-negative bacteria”, by Steven Rutherford, Senior Scientist, Infectious Disease, Genentech.

Abstract: Multi-drug resistant bacteria are a global health threat and new strategies are needed to combat them. However, the discovery of novel antibiotics to treat infections by Gram-negative bacteria has been thwarted by the outer membrane, a permeability barrier that excludes cytotoxic compounds from these cells. My laboratory has identified both large and small molecules that interfere with outer membrane biogenesis by targeting the essential proteins BamA and LptD on the bacterial cell surface, thus avoiding the outer membrane penetration problem. These molecules have validated BamA and LptD as potential antibacterial targets and revealed novel insights into the structures and functions of the only two essential outer membrane proteins.

Monday, November 16, 2020 2:30pm. Join by Zoom.

Hosted by Dr. Franck Duong

“The interactive behaviour of white-collar workers in biological systems.” by Dr. Joerg Gsponer, Biochemistry and Molecular Biology, Michael Smith Laboratories, UBC.

Monday, October 19, 2020 at 2:30 pm. Join by Zoom.

Hosted by Dr. Leonard Foster

“Three-Dimensional Transmission and Scanning Electron Microscopy of Molecular and Cellular Structures,” by Brian Caffrey, Candidate Subramaniam Lab.

Abstract: Unravelling the complex spatial arrangement of networks and interfaces between proteins, cells and tissues is fundamental to our understanding of healthy and pathological processes. Therefore, a three-dimensional ultrastructural understanding of this arrangement is key to developing modern diagnostic and therapeutic applications in disease. Here, we discuss our application of transmission and scanning electron microscopy techniques such as the Cryo-Electron Microscopy (Cryo-EM) analysis of disease-related mutant protein dynamics; using Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM) to elucidate the 3D structure of muscular mitochondria and in combination with light microscopy, to study nanoparticle-cell interactions.

Zoom presentations – Monday, October 5th, 2020 from 2:30 – 3:00 pm. Zoom link emailed to department members.

“Structural Characterization of the Bacterial Injectisome,” by Dorothy Majewski, PhD Candidate, Strynadka Lab.

Abstract: The injectisome is a syringe-like protein complex essential for the virulence of many Gram-negative pathogenic bacteria. As a potential target for drug and vaccine design, studies to elucidate its structure have been ongoing over the past two decades. Two components of this system are essential to its function: the pore-assembling pilotin, and the cytosolic ATPase. Through X-ray crystallography, nuclear magnetic resonance, and cryo-electron microscopy, we have solved the structures of these proteins and learned key details about their interfaces with other members of the injectisome complex. Biochemical experiments have further improved our understanding of the binding and enzyme kinetics of these proteins. These structures have given us insight into injectisome assembly and function, forming a basis for future drug design.

Monday, September 14, 2020 at 2:30, join by Zoom.