QUEEN'S BIOLOGY MCIB SEMINAR SERIES
  • Home
  • Schedule
  • Contact

Seminar series of the Molecular, Cellular & Integrative Biology
research groups at Queen's University

Tues Mar 2 // Dr. Che Colpitts // Department of Biomedical and Molecular Sciences, Queen's University

2/25/2021

 
Picture

Dr. Che Colpitts
​Department of Biomedical and Molecular Sciences, Queen's University

One drug to rule them all: Novel antiviral strategies for coronaviruses and beyond

The ongoing COVID-19 pandemic underscores our vulnerability to emerging viruses. Most emerging viruses are zoonotic and jump into humans from animal reservoirs as a result of habitat destruction and ecosystem disruption. As such, we are likely to face future pandemic threats from emerging viruses. Conventional antiviral development relies on detailed characterization of viral enzymes and is not compatible with a rapid response to newly emerging viruses. Rather than pursue a traditional “one bug, one drug” approach to antivirals, we aim to identify and characterize highly conserved virus-host interactions as targets for broadly-acting antivirals to protect against emerging, and yet to emerge, viruses. Many viruses have evolved to attach to cell-surface carbohydrates called glycans as the first step in infection. We have shown that disrupting these glycan-dependent interactions broadly inhibits the cellular entry of unrelated viruses, including hepatitis C virus, herpesviruses, influenza virus, and others. Similarly, many viruses require interaction with a cellular protein called cyclophilin A to successfully replicate in cells. We showed that hepatitis C virus requires cyclophilin A to evade cell-intrinsic antiviral immunity. We are currently characterizing the roles of glycans and cyclophilins in replication of SARS-CoV-2 and other coronaviruses, and are applying this knowledge to define novel antiviral strategies against coronaviruses. These studies inform the development of broadly-acting antivirals to protect against current and future emerging viruses.

Tues Feb 23 // Dr. Melissa Bredow // Monaghan Lab, Queen's University

2/18/2021

 
Picture

Dr. Melissa Bredow
Postdoctoral Fellow, Monaghan Lab, Queen's University
Exploring site-specific modification as a tool to direct pathway specific activity of the multifunctional calcium-dependent protein kinase CPK28

​Calcium (Ca2+) is a ubiquitous secondary messenger involved in most adaptive and developmental signaling programs in plants. Spatially and temporally defined influxes of intracellular Ca2+, known as Ca2+ signatures, are generated in response to environmental cues and are “decoded” by intracellular proteins. Ca2+-dependent protein kinases (CDPKs) are a unique family of Ca2+ sensors that can both perceive Ca2+ and propagate intracellular signals. Many CDPKs serve roles in several pathways and therefore must be capable of decoding distinct Ca2+ signatures. How stimuli specific Ca2+ signatures are distinguished has remained an outstanding and compelling question. In our work, we explore site-specific phosphorylation as a regulator of Ca2+ sensitivity on Arabidopsis CPK28.  We show that phosphorylation at an individual residue (Ser318) dictates the level of Ca2+ required for kinase activation and directs pathway-specific activity of CPK28 in vivo. CPK28 is a negative regulator of immune signaling and also functions in the vegetative-to-reproductive stage transition. Generating a CPK28 allele that could not be phosphorylated at Ser318 resulted in enhanced immunity to bacterial infection without consequences to reproductive growth observed in cpk28 loss-of-function plants. Biochemical analysis indicated that Ser318 phosphorylation promoted a change in protein conformation that “primed” CPK28 for rapid Ca2+ activation, necessary for immune function. In contrast, Ser318 phosphorylation was not required for reproductive growth indicating pathway specific requirements for rapid Ca2+ activation. Further, we identify additional CPK28 phospho-mutant alleles that direct pathway specific activity, enhancing bacterial immunity and promoting plant growth. Ongoing work is aimed at understanding the evolution of multifunctionality in CDPKs and suggests that CPK28 belongs to an ancient core immune pathway. Together, our work points towards a conserved mechanism of Ca2+ priming in CPK28 orthologs and highlights the use of the site-specific modifications to generate stress-resilient plants without fitness costs.  

Tues Feb 9 // Dr. Touati Benoukraf // Discipline of Genetics, Faculty of Medicine, Memorial University

2/4/2021

 
Picture

Dr. Touati Benoukraf
Faculty of Medicine, Memorial University
Interplays between DNA methylation and transcription factor binding events

DNA methylation plays an essential role in gene regulation and chromatin remodeling. Accumulative evidence brought to light an interplay between the recruitment of transcription factors (TF) and DNA methylation, which attenuates the dogma that DNA methylation is strictly associated with the heterochromatin state. Using a large set of public data, we built MethMotif (http://methmotif.org), a database that records precisely TF binding sites (TFBS) along with their DNA methylation status, in a cell-specific manner. MethMotif compiles ~650 TFBS position weight matrices across 17 cell types, in human and mouse cells, computed from 2300 ChIPSeq and 23 whole-genome bisulfites sequencing (WGBS) datasets. In parallel, we launched TFRegulomeR, an R library that allows the manipulation of our data compendium. In particular, TFRegulomeR facilitates the characterization of methyl-specific transcription factor modules. Interestingly, our integrative analyses have brought to light a novel chromatin state: the primed heterochromatin, which is associated with methylated ZBTB33 binding sites. Indeed, these sites are located within condensed chromatin which is inaccessible to DNase I and Tn5 transposase and carries a newly revealed histone post-translational modification signature with significant enrichment of mono-methylation at lysine 4 of histone 3 (H3K4me1) and a complete absence of other active or expected repressive histone marks. In other words, our analyses revealed that ZBTB33 has the unique ability to bind methylated DNA across the heterochromatin, in a transition state, suggesting a potential role for ZBTB33 in heterochromatin priming.

    Archives

    February 2021
    January 2021
    December 2020
    November 2020
    October 2020
    September 2020
    August 2020
    June 2020
    April 2020
    March 2020
    February 2020
    January 2020
    November 2019
    October 2019
    September 2019
    August 2019
    July 2019
    May 2019
    April 2019
    March 2019
    February 2019
    January 2019
    November 2018
    October 2018
    September 2018
    June 2018
    May 2018
    April 2018
    March 2018
    February 2018
    January 2018
    November 2017
    October 2017
    September 2017
    June 2017
    May 2017
    April 2017
    March 2017
    February 2017
    January 2017
    December 2016
    November 2016
    October 2016
    September 2016
    August 2016

Powered by Create your own unique website with customizable templates.
  • Home
  • Schedule
  • Contact