“Staphylococcal protein A is flexible and conformationally heterogeneous: how do we observe and describe its structure?” by Terrence G Oas, Professor, Department of Biochemistry and Chemistry, Duke University.
Monday, October 19, 2015
LSC 3 at 3:00 pm, 2350 Health Sciences Mall
“Role for drug delivery formulations to capture the benefits of chemical synthetic lethal interactions,” by Dr. Marcel Bally, Head and Distinguished Scientist, Department of Experimental Therapeutics of BC Cancer Agency.
Monday, September 28, 2015 @ 3:00 pm, LSC #3, 2350 Health Sciences Mall.
Gairdner Symposium: Michael N Hall and Yoshinori Ohsumi, Gairdner 2015 Symposium Vancouver
Monday, October 26, 4-6 pm
Life Science Center, Lecture #2, UBC 2350 Health Sciences Mall
Michael N Hall, PhD
Recipient of the Canada Gairdner International Award, 2015
“for his discovery of the nutrient activated protein kinase TOR and elucidation of its central control of cell growth, critical to development and aging and widely implicated in cancers, diabetes, cardiovascular and immune diseases“
Professor, Biozentrum, University of Basel, Switzerland
Presentation Title: TOR signalling in growth and metabolism
To learn more about Dr. Hall: http://www.gairdner.org/content/michael-n-hall
Yoshinori Ohsumi, DSc
Recipient of the Canada Gairdner International Award, 2015
“for pioneering the molecular elucidation of autophagy, an essential intracellular, degradation system and when disordered, is linked to many diseases including neurodegeneration, cancer, and infection”
Honorary Prof, Dept. of Frontier Research Center, Tokyo Institute of Technology
Presentation Title: Lessons from Yeast – Intracellular recycling system, autophagy
For information about Dr. Ohsumi:http://www.gairdner.org/content/yoshinori-ohsumi
Thesis title, “Structure, proteolysis, and evolution of secreted tuberculosis virulence factors,” Matthew Solomonson.
Monday, July 27, 2015 at 1:00 pm, Rm 5310, Life Sciences Centre, 2350 Health Science Mall
ABSTRACT
Mycobacterium tuberculosis (TB) uses the ESX-1 type VII secretion system to export proteins to its cell surface, which permeabilize the host macrophage phagosomal membrane, allowing the bacterium to escape and spread to new cells. The structure of the type VII membrane complex and how it mediates this function is unknown, but it is hypothesized that some of the secreted proteins form an extracellular appendage that facilitates membrane lysis or direct secretion of virulence factors into the host cytoplasm. This thesis investigates the structural relationship between one of these secreted proteins, EspB, and a protease that processes it, MycP1. The x-ray crystallographic structures of both proteins are determined. EspB is shown to form a multimer with heptameric stoichiometry, and an EM reconstruction of this multimer is generated and used to create a model of the oligomer using symmetric Rosetta docking. The final model is supported by mass spectrometry-based detection of chemically cross-linked peptides from adjacent subunits. We use mass spectrometry to determine how EspB is proteolytically processed during secretion and discuss the effect of this processing event on the EspB ultrastructure. Finally, the structure of one of the membrane apparatus proteins, EccB1 is determined, revealing structural homology to a phage lysin. The combination of x-ray crystallography, EM, modeling, and mass-spectrometry provides an exciting first glimpse at the structure and function of the type VII secretion system – a critical factor in the TB pathogenesis cycle.
“Characterization of Cricket Paralysis Virus Virus-Host Interaction and Viral Protein Synthesis,”
by Anthony Khong, Doctoral Student in Eric Jan Lab.
Tuesday, July 28, 2015 9:00 AM – Room 1410, Life Sciences Centre, 2350 Health Sciences Mall
“Structural and functional characterization of type III secretion system components,”by Brianne Burkinshaw, Doctoral Candidate in Natalie Strynadka Lab
“Structure, proteolysis, and evolution of secreted tuberculosis virulence factors,” by Matthew Solomonson, Doctoral Candidate in Natalie Strynadka Lab
Monday, July 20, 2015, LSC 3 at 3:00 pm, 2350 Health Science Mall
Thesis title, “Structure, proteolysis, and evolution of secreted tuberculosis virulence factors,” Matthew Solomonson.
Monday, July 27, 2015 at 1:00 pm, Rm 5310, Life Sciences Centre, 2350 Health Science Mall
ABSTRACT
Mycobacterium tuberculosis (TB) uses the ESX-1 type VII secretion system to export proteins to its cell surface, which permeabilize the host macrophage phagosomal membrane, allowing the bacterium to escape and spread to new cells. The structure of the type VII membrane complex and how it mediates this function is unknown, but it is hypothesized that some of the secreted proteins form an extracellular appendage that facilitates membrane lysis or direct secretion of virulence factors into the host cytoplasm. This thesis investigates the structural relationship between one of these secreted proteins, EspB, and a protease that processes it, MycP1. The x-ray crystallographic structures of both proteins are determined. EspB is shown to form a multimer with heptameric stoichiometry, and an EM reconstruction of this multimer is generated and used to create a model of the oligomer using symmetric Rosetta docking. The final model is supported by mass spectrometry-based detection of chemically cross-linked peptides from adjacent subunits. We use mass spectrometry to determine how EspB is proteolytically processed during secretion and discuss the effect of this processing event on the EspB ultrastructure. Finally, the structure of one of the membrane apparatus proteins, EccB1 is determined, revealing structural homology to a phage lysin. The combination of x-ray crystallography, EM, modeling, and mass-spectrometry provides an exciting first glimpse at the structure and function of the type VII secretion system – a critical factor in the TB pathogenesis cycle.
“RNA granules at the nexus of stress and innate immunity”, by Richard E. Lloyd, Professor, Department of Molecular Virology and Microbiology, Baylor College of Medicine. Tuesday, July 28, 2015 @ 3:00 pm, LSC #3, 2350 Health Sciences Mall.
Thesis title, “Structural and Functional Characterization of Components of Bacterial Type III Secretion Systems,” by Brianne Burkinshaw.
Monday, July 20, 2015 at 9:00 am, Rm 203, Graduate Student Centre, 6371 Crescent Road.
ABSTRACT
Many Gram-negative pathogens use a type III secretion system (T3SS) to
inject effector proteins into the host cytoplasm, where they manipulate host processes
to the advantage of the bacterium. The T3SS is composed of a cytoplasmic export
apparatus, a membrane-spanning basal body with a central channel formed by the
inner rod, an extra-cellular needle filament and a translocon complex that inserts in
the host membrane. In this thesis, proteins involved in T3SS assembly, as well as a
T3SS effector protein were structurally and functionally characterized. The structure
of EtgA, a T3SS-associated peptidoglycan (PG)-cleaving enzyme from EPEC was
solved. The EtgA active site has features in common with lytic transglycosylases
(LTs) and hen egg-white lysozyme (HEWL). EtgA contains an aspartate that aligns
with lysozyme Asp52 (a residue critical for catalysis), a conservation not observed in
LT families to which the conserved T3SS enzymes were presumed to belong.
Mutation of the EtgA catalytic glutamate conserved across LTs and HEWL, and this
differentiating aspartate diminishes type III secretion in vivo, supporting its essential
role in T3SS assembly. EtgA forms a complex with the T3SS inner rod component,
which enhances PG-lytic activity of EtgA in vitro, providing localization and regulation
of the lytic activity to prevent cell lysis. After assembly of the basal body and needle,
the gatekeeper protein ensures the translocon assembles at the needle tip prior to
secretion of effector proteins. The gatekeeper from EPEC (SepL) was crystallized and
it was shown that it has three X-bundle domains, which likely mediate protein-protein
interactions to control translocon and effector secretion. Through comparison of
SepL to structurally characterized homologs, revealed a number of conserved
residues, which may be required to regulate secretion of translocators or effectors.
Finally, SopB, a Salmonella effector protein, in complex with host Cdc42, an essential
Rho GTPase that regulates critical events in eukaryotic cytoskeleton organization and
membrane trafficking was structurally characterized. Structural and biochemical
analysis of the SopB/ Cdc42 complex shows that SopB structurally and functionally
mimics a host guanine nucleotide dissociation inhibitor (GDI) by contacting key
residues in the regulatory switch regions of Cdc42 and slowing Cdc42 nucleotide
exchange.
Biochemistry welcomes two new Associate Members: Dr. Hugh Kim and Dr. Harry Brumer. Dr. Hugh Kim, an Assistant Professor in the Faculty of Dentistry is a Principal Investigator in The Centre for Blood Research, UBC. Dr. Brumer is a full professor who holds joint appointments in both Chemistry and The Michael Smith Laboratories.
