Posted on September 16, 2022
Title: Unraveling RNA virus-host interactions reveals novel antiviral targets.
Professor. Department of Cell Biology.
University of Alberta
Abstract: RNA virus infections impose huge economic and social burdens around the globe. Direct-acting antiviral therapeutics and vaccines can be highly effective in controlling epidemic and pandemic viruses, but these drugs/prophylactics take time to develop and their efficacy is often limited to specific viral strains. To minimize the impact of future emerging RNA viruses, a stockpile of broad-spectrum antivirals is required to serve as a first line of defense against these pathogens. Identification of host cell-based pathways that are exploited or inhibited by multiple viruses is expected to reveal novel targets for antiviral therapy. Using targeted and unbiased screening approaches, we have identified multiple host cell pathways that can be pharmacologically inhibited or enhanced to reduce infection by multiple RNA viruses including SARS-CoV-2..
Monday, September 26, 2022 at 2:30 pm at LSC 3 and Zoom
Hosted by: Dr. Eric Jan
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Posted on September 8, 2022
The Department of Biochemistry & Molecular Biology is pleased to announce the appointment of Dr. Eden Fussner-Dupas as Assistant Professor of Teaching! Dr. Fussner-Dupas will be teaching BIOC 302 this fall.
Dr. Fussner-Dupas’ profile page: https://biochem.ubc.ca/person/eden-fussner-dupas/
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Posted on August 31, 2022
Title: Blood clot stability can be controlled using lipid nanoparticle-delivered siRNA
Abstract: Disruptions in the balance of clot formation and degradation can lead to dangerous, potentially fatal, clotting or bleeding events. While a plethora of research tools and clinical therapies exist to control clot formation, options for controlling clot degradation are extremely limited. RNA and lipid-based technologies can be applied to the field of hematology and meet the need for long-acting agents to control the stability of clots. This work developed siRNA-LNP agents that increase or decrease the durability of clots in three model species, enabling further investigation of this pathway as a target for research in a wide range of coagulation disorders.
Monday, September 19, 2022 at 2:30 pm – 3:30 pm via Zoom
Hosted by: Dr. Christian Kastrup
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Posted on August 30, 2022
Title: Ensemble-based computational design of enzyme catalysis and conformational equilibrium.
Professor, Department of Chemistry and Biomolecular Sciences.
University of Ottawa
Abstract: Enzymes are dynamic molecules, and this flexibility is essential to their catalytic function. Yet, computational enzyme design is typically performed using a single protein scaffold as design template, ignoring the important contributions of dynamics in enzyme catalysis. In the past few years, my group has developed multistate computational protein design methods that allow proteins to be modelled as structural ensembles that more realistically represent the range of conformations that these molecules can adopt. Here, I will show how we can use structural ensembles to accurately design more efficient de novo enzymes than previously possible and remodel an enzyme conformational landscape to obtain an 1800-fold substrate selectivity switch.
Monday, September 12, 2022 at 2:30 pm at LSC 3 and Zoom
Hosted by: Dr. Nobuhiko Tokuriki
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Posted on August 24, 2022
Title: Dissecting the biophysical properties and DNA-binding specificity of the ETV6 transcription factor
Abstract: Transcription factors bind to specific DNA sequences and regulate the expression of associated genes. In this thesis, I used several biophysical methods to investigate the structure and DNA-binding specificity profile of the eukaryotic transcription factor ETV6. I investigated the mechanisms by which ETV6 selectively binds its cognate DNA targets. ETV6 prefers DNAs containing a core GGAA motif, unlike other family members where GGA(A/T) is accepted. This specificity toward the fourth adenine is mediated by a single histidine, His396, contrasted with a tyrosine in other family members. Through NMR-monitored pH titrations, I found His396 adopts the neutral Nε2H tautomeric state when ETV6 is both free and DNA-bound. Both structural and surface plasmon resonance binding studies revealed the mutation of His396 to a tyrosine increased its affinity for GGAT-containing DNA, while not diminishing its affinity for DNAs with a GGAA core. Thus I propose that His396 does not serve to enable binding of DNA containing a GGAA core, but rather to disfavour association toward DNAs containing bases other than an adenine at this fourth position. This thereby restricts the transcriptional profile of ETV6 relative to other ETS factors. In a related study I investigated conformational flexibility within the DNA-binding domain of ETV6. All ETS family proteins share a structurally conserved ETS domain, allowing association toward many redundant DNA sequences. These proteins can also recognize subtly different DNA regions to enable transcriptional specificity. I proposed a contributing factor toward the profile of DNAs each family member recognized was domain flexibility. Testing this, I introduced cavity-forming mutations in the ETV6 ETS domain, resulting in increase flexibility determined through relaxation-dispersion NMR experiments. Then, using microarrays, I showed the increase in flexibility weakened selection of near-cognate DNAs, and thereby increased the specificity for cognate DNAs. These flexibility changes predominantly affected selection of DNA bases contacted solely via their phosphodiester backbone, indicating a link between protein flexibility and specificity for the sequence-dependent shape of DNA. Collectively my thesis uncovered many biophysical properties of the ETV6 ETS domain and illustrated how these features contribute to its DNA binding specificity at a molecular level.
Monday, August 29, 2022 at 2:30 pm – 3:30 pm via Zoom
Hosted by: Dr. Lawrence McIntosh
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Posted on August 22, 2022
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Posted on August 2, 2022
Title: The role of the actin cytoskeleton in regulating platelet lifespan and function
Abstract: Platelets are small discoid blood cells that regulate hemostasis and wound healing. Normal platelet function is largely contingent on the shape change reaction that occurs following the cells’ exposure to external stimuli and/or soluble agonists. Agonist-driven platelet shape change is mediated by reorganizations of the actin cytoskeleton (the cell’s structural framework) although the associated molecular mechanisms are not precisely defined. Moreover, platelet lifespan is partly determined by apoptosis (programmed cell death); how the actin cytoskeleton regulates platelet apoptosis is also undefined. My work is focused on how the actin cytoskeleton, and how specific actin-binding proteins such as gelsolin (GSN) and filamin A (FLNA), regulate apoptosis in platelets. A better understanding of the mechanisms underlying platelet survival is key to discovering improved treatments for potentially life-threatening diseases such as idiopathic thrombocytopenic purpura.
Monday, August 08, 2022 at 2:30 pm – 3:30 pm via Zoom
Hosted by: Dr. Hugh Kim
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