Dr. Marie-Laurence Lemay Département de microbiologie, infectiologie et immunologie, Université de Montréal Fundamental and applied research in dairy microbiology: a phage scientist’s perspective
As a graduate student in the lab of Prof. Sylvain Moineau, Canada Research Chair in Bacteriophages, I got to experience discovery-based research by studying phages infecting Lactococcus lactis, a workhorse of the dairy industry. As a microbiology specialist for Agropur, one of North America's leading dairy processors, I got to experience applied research in industry. In this seminar, I will share my experience in both settings, and I will discuss the advantages of academic-industrial partnerships by presenting an overview of a collaborative research effort spanning almost two decades to establish a phage monitoring program. By partnering with phage scientists, dairy industries can access specialized expertise to develop or optimize rational solutions to respond to phage problems. By partnering with dairy industries, phage scientists can access valuable samples to study phage population dynamics and fill knowledge gaps in our understanding of phage biology. In the end, fundamental and applied research are two sides of the same coin; it all comes down to creating new knowledge that can be applied to dairy microbiology and far beyond.
Dr. Maria Tokuyama Department of Microbiology and Immunology, University of British Columbia Exploring the genomic dark matter: immunomodulatory roles of endogenous retroviruses
Endogenous retroviruses (ERVs) make up 8% of the human genome, yet their functional role in immunity is not well understood. My research program is focused on how ERVs modulate the immune system in the context of autoimmunity and antiviral response. Through the development of a bioinformatics pipeline called ERVmap to analyze the human ERV transcriptome, my work uncovered unique sets of ERVs that define cell types and disease states and identified an ERV envelope protein that promotes neutrophil activation in lupus. We have also uncovered a protective role of ERVs against mucosal viral challenge. This seminar will be an overview of these projects and future projects in the Tokuyama lab.
Dr. Donovan German Department of Ecology and Evolutionary Biology, University of California, Irvine Unlocking the mysteries of the inner tube of life: a gut-eyed view of nutritional ecology
Among the multitude of physiological processes, those that influence energy and resource acquisition are the most likely to have an effect on an animal’s behavior, ecological and trophic interactions. However, given the importance of digestive processes in determining an animal’s ecology, digestive physiology is not investigated as often as might be warranted. In this seminar, I will share how studying the digestive physiology and biochemistry of different animals provided insight into their ecology not granted by studying diet alone. I will start by exploring digestion in seagrass-eating bonnethead sharks from the Gulf of Mexico, the first confirmed omnivorous shark. I will then continue by investigating the genomic underpinnings of dietary specialization in a marine herbivorous fish, emphasizing the role of lipases and lipids in an herbivorous diet. This work has strong implications for the future of sustainable aquaculture. I will conclude by delving into our newer investigations into the enteric microbiomes of various taxa, and how there may be feedbacks between what the gut is secreting into the distal intestine, and what microbes establish there. Overall, the gut is a dynamic biochemical system that has been relatively understudied in terms of its role in ecology and evolution. Indeed, interest in the human digestive tract (and microbiome) has also increased in recent years. I hope to pique your curiosity through interesting examples and investigation of the alimentary canal in different animal models and make the links to our own “inner tube of life”.
Discussion of: Michael B Eisen's recorded talk at the University of Alberta "Reinventing science publishing"
Are you curious about preprints? Passionate about open science? Do you think impact factors are a flawed measure? Do we even need journals?? Who better to learn about the state of science publishing than from Michael B Eisen, Professor at UC Berkeley, co-founder of PLoS and the Editor in Chief at eLife. Recently, Dr Eisen presented a thought-provoking, meme-filled seminar at the University of Alberta, which was recorded. So, we thought we’d do something a bit different for the MCIB Seminar next week:
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.
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.
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.
Bryden O'Gallagher MSc Candidate, Plaxton Lab, Queen's University Exploring the role of the dual-targeted 'mammalian type' purple acid phosphatase AtPAP17 in Arabidopsis thaliana phosphate and ROS metabolism
Orthophosphate (H2PO4-, Pi) is an essential, but environmentally limiting macronutrient required for many fundamental metabolic processes. Pi starved (–Pi) plants undergo a complex array of morphological and biochemical/molecular adaptations, collectively known as the ‘Pi starvation response’. Purple acid phosphatases (PAPs) play an indispensable role in the PSR by scavenging and recycling Pi from intra- and extracellular Pi-monoesters. The aim of this thesis has been to integrate biochemical and genetic approaches to help assess the role of AtPAP17 (one of 29 predicted Arabidopsis PAPs) in Pi and ROS metabolism. AtPAP17 is unique to previously characterized PAPs as it: i) is transcriptionally induced in response to Pi-starvation, leaf senescence, salinity, drought, as well as immune-related biotic stress, and ii) exists as a low molecular weight (35 kDa) ‘mammalian like’ PAP that exhibits both acid phosphatase and peroxidase activity. I determined the H2O2 peroxidase kinetics of purified AtPAP17, while demonstrating that this PAP is de novo synthesized and dual-targeted to the secretome and intracellular fraction of –Pi, senescing, or salt stressed Arabidopsis, but rapidly turned over following Pi resupply to –Pi plants. Nevertheless, loss of AtPAP17 expression in an atpap17 mutant did not influence the ability of Arabidopsis to acclimate to Pi deprivation, salinity or oxidative stress, or to recycle Pi during leaf senescence. This research field is enabling the development of innovative strategies for engineering Pi-efficient and stress-tolerant crops, urgently needed to reduce inputs of unsustainable Pi fertilizers for maximum agronomic benefit and long-term global food security and ecosystem preservation.
Howard Teresinki PhD Candidate, Snedden Lab, Queen's University Identification and characterization of novel targets for a subfamily of Arabidopsis calmodulin-like (CML) proteins
Calcium is a ubiquitous second messenger in signal transduction pathways of all eukaryotic cells. In plants, calcium signalling plays critical roles in a variety of developmental processes as well as during cellular responses to abiotic and biotic stress. The evolutionarily-conserved calcium sensor, Calmodulin (CaM), responds to calcium signals and, through protein-protein interactions in cells, facilitates downstream responses. Plants possess an additional and unique family of “calmodulin-like” (CML) calcium sensors which, in Arabidopsis thaliana, contains 50 members. Despite this expanded complexity, few of the binding partners and/or in vivo functions of CMLs are known. Here I present data from my PhD thesis demonstrating that CaM and a subfamily of biochemically unusual CMLs are capable of interacting with specialized structural domains from among three distinct and unrelated protein families in Arabidopsis. I utilised a combination of genetic, biochemical, and biophysical approaches to explore the physical properties and physiological roles of CML interactions with these putative targets. Collectively, my data suggests novel functions for plant CMLs in gene regulation and cytoskeletal activity.