CSB Seminar: Alexander Mosa, A Novel Approach to Polyvalent Vaccine Design for Hyper-Variable Viruses
“A Novel Approach to Polyvalent Vaccine Design for Hyper-Variable Viruses”
Alexander Mosa, Post-doctoral fellow
Institute of Medical Science, University of Toronto
Abstract:
Friday, May 14th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Mounir Abouhaidar
CSB Seminar: Peter Swain, University of Edinburgh
Title: Using a push-pull system of repressors to match glucose transporters to extracellular glucose
Peter Swain
University of Edinburgh
Abstract: A common cellular task is to match gene expression dynamically to a range of concentrations of a regulatory molecule. Studying glucose transport in budding yeast, we determine mechanistically how such matching occurs for seven hexose transporters. By combining time-lapse microscopy with mathematical modelling, we find that levels of transporters are history-dependent and are regulated by a push-pull system comprising two types of repressors. I will argue that matching is favoured by a rate-affinity trade-off and that the regulatory system allows yeast to import glucose rapidly enough to starve competitors.
Friday, June 4, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Alan Moses
CSB Seminar: Thinking of cells as composites of materials: a way to understand shaping of the early Drosophila embryo by cytoskeletal networks
“Thinking of cells as composites of materials: a way to understand shaping of the early Drosophila embryo by cytoskeletal networks”
Tony Harris and Medha Sharma
Cell and Systems Biology
Abstract:
A major question in biology is how cells form and function through the coordinated activities of their molecular components. Tony will describe how this question can be approached by thinking of cells as composites of materials. What signals and components form each material? What are the chemical and physical properties of each material? How do the materials affect each other for chemical and physical change at the cellular scale? These points will be discussed in relation to the cell cortex, a layer of actin networks and additional factors beneath the plasma membrane. Tony will review how the activities and interactions of cortical domains produce dome-like compartments for dividing nuclei of the syncytial Drosophila embryo. Medha will discuss her PhD research focused on a central aspect of this cortical reorganization—how a smooth boundary can form between rough-edged cortical domains. Across the syncytial embryo surface, smooth interfaces form between expanding Arp2/3-based actin caps and surrounding actomyosin networks, demarcating the circumferences of nascent dome-like compartments. The smoothening of the actomyosin interfaces requires Arp2/3 in vivo. To dissect the physical basis of this requirement, Medha reconstituted the interacting networks using node-based models. When actomyosin networks were simulated with clearances instead of Arp2/3 networks, rough boundaries persisted with low levels of myosin contractility. With addition of expanding Arp2/3 networks, network-network interfaces failed to smoothen, but accumulated myosin nodes and tension. After incorporating actomyosin mechanosensitivity, Arp2/3 network growth induced local contractility and smoothening of the interfaces, effects also evident in vivo. In this way, a smooth structure can emerge from the lateral interaction of irregular starting materials, an early step of budding a dome-like compartment from a much larger cell.
Friday, April 30th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Tony Harris (tony.harris@utoronto.ca)
CSB Seminar: Force-dependent activation of actin elongation factor mDia1 protects the cytoskeleton from mechanical damage and facilitates stress fiber repair
“Force-dependent activation of actin elongation factor mDia1 protects the cytoskeleton from mechanical damage and facilitates stress fiber repair”
Sergey Plotnikov
Assistant Professor
Department of Cell and Systems Biology, University of Toronto
Fernando Valencia
PhD Candidate
Department of Cells and Systems Biology, University of Toronto
Abstract:
Cells are truly the ultimate “smart-material” fine-tuning their mechanical properties to match the mechanical demands of their environments. Such plasticity of cell mechanics, which relies heavily on the spatiotemporal regulation of the actomyosin cytoskeleton, allows cells to migrate through narrow spaces, resist shear forces, and safeguard against mechanical damage. Yet, mechanisms of the adaptive changes in cell mechanics remain elusive. In this presentation, we will report a new mechanism whereby mechanically activated actin elongation factor mDia1 controls the dynamics of actin polymerization at focal adhesions, force bearing linkages between the actin cytoskeleton and extracellular matrix. By combining live-cell imaging with mathematical modelling, we show that actin polymerization at focal adhesions exhibits pulsatile dynamics where the spikes of mDia1 activity are triggered by cell-generated contractile forces. We show that suppression of mDia1-mediated actin polymerization at focal adhesions results in two-fold increase in mechanical tension on the stress fibers. This elevated tension correlates with an increased frequency of spontaneous stress fiber damage and decreased efficiency of zyxin-mediated stress fiber repair. Finally, we show that stress fiber protection by mDia1 is essential for differentiation of myofibroblasts, a highly contractile cells that are vital for wound healing. We conclude that tension-controlled actin polymerization at focal adhesions acts as a safety valve dampening excessive mechanical tension on the actin cytoskeleton and safeguarding stress fibers against mechanical damage.
Friday, March 19th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Sergey Plotnikov (sergey.plotnikov@utoronto.ca)
CSB Seminar: How to make microtubules and build the cytoskeleton
“How to make microtubules and build the cytoskeleton”
Sabine Petry
Associate Professor, Department of Molecular Biology
Princeton University
Abstract:
“How does a cell construct its microtubule cytoskeleton? According to Feynman’s principle “what I cannot create, I do not understand”, my lab pursues this question by building the chromosome segregation machinery from scratch. I will first tell you how the microtubule framework is generated in a cell. Upon deciphering the function of the most important microtubule accessory proteins, I will present how we use those building blocks to reconstitute a spindle substructure in vitro and determine its building plan. Finally, I will outline how we combine spindle substructures like pieces of a puzzle to assemble and thereby understand a functioning spindle that segregates chromosomes.
By studying how the MT cytoskeleton is built, I hope to help explain how hundreds of proteins can self-assemble on the nm scale into a complex molecular machine 1000-fold larger than its constituents, a challenge for the biochemistry of the 21st century.”
Friday, April 23rd, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Student invited speaker (Ernest Iu and Steven Chen)
CSB Seminar: Pollen and its coat – ‘smart’ dressing for the mating game
“Pollen and its coat – ‘smart’ dressing for the mating game”
James Doughty
Dept of Biology and Biochemistry
University of Bath, UK
Abstract:
The earliest steps of plant reproduction involve an intimate interaction between male and female reproductive structures namely the pollen grain, a vehicle for delivering sperm, and the surface of the stigma which ‘screens’ incoming pollen for compatibility. The establishment of the pollen-stigma interaction is proposed to involve a basal compatibility system that enables compatible pollen to be recognised by the receptive stigma. A key aspect of the work in our lab has been focussed on identifying the signals carried on the surface of pollen (in the pollen coat) that permit stigmas to respond in the appropriate manner to potential partners (partners could be from the same or different species). Through proteomic analysis across three species of the Brassicacaeae (Arabidopsis thaliana, Arabidopsis lyrata and Brassica oleracea) we have uncovered an extraordinary diversity of small cysteine-rich proteins that make up a significant proportion of the pollen coat proteome. Studies to date indicate that several of these small proteins play a role in the initial molecular conversation between pollen and stigma. Our goal is to describe the pollen coat proteome and functionally characterise these proteins with the ultimate goal of identifying their molecular targets in female reproductive tissues.
Friday, April 16th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Daphne Goring (d.goring@utoronto.ca)
CSB Seminar: Exerting and sensing forces during integrin-mediated phagocytosis
“Exerting and sensing forces during integrin-mediated phagocytosis”
Valentin Jaumouillé, Assistant Professor
Department of Molecular Biology and Biochemistry, Simon Fraser University
Abstract:
Professional phagocytes are innate immune cells specialized in the uptake and clearance of large particulate materials including infiltrated microbes, apoptotic cells and debris. αMβ2 integrins (also called complement receptor 3) are highly expressed in macrophages and neutrophils. These integrins are thought to be the main phagocytic receptors for many pathogens, and participate in the clearance of dead cells and cancer cells. However, internalization of these different targets involve various physical constraints that professional phagocytes must overcome, including cortical and membrane tensions. In other contexts, such as cell adhesion and migration, cells deform and move using surface-attached integrins, which are coupled to mechanical forces generated by the actin cytoskeleton. By analogy, we asked whether phagocytosis required mechanical coupling of αMβ2 integrins to the actin cytoskeleton. Using quantitative live cell imaging, we found that particle internalization was driven by formation of Arp2/3 and formin-dependent actin protrusions that wrapped around the particle. Focal complex-like adhesions formed in the phagocytic cup, which contained β2 integrins, focal adhesion proteins and tyrosine kinases. Perturbation of talin and syk demonstrated that a talin-dependent mechanical link between integrins, and actin and a syk-mediated recruitment of vinculin independently of myosin II, enabled force transmission to target particles and promoted phagocytosis. Altering target mechanical properties demonstrated more efficient phagocytosis of stiffer targets, which could enable the discrimination of different targets based on their mechanical properties. Thus, macrophages build a myosin II-independent mechanosensitive molecular clutch, which couples integrins to cytoskeletal forces to control particle engulfment.
Friday, April 9th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Sergey Plotnikov (sergey.plotnikov@utoronto.ca)
CSB Seminar: Prof Esther Verheyen on Insights into human disease mechanisms using Drosophila: Cdk8 regulates a Parkinson’s Disease Model
“Insights into human disease mechanisms using Drosophila: Cdk8 regulates a Parkinson’s Disease Model”
Esther Verheyen, Professor
Molecular Biology and Biochemistry
Co-Director, Centre for Cell Biology, Development and Disease
Simon Fraser University
Abstract:
Cyclin-dependent kinase 8 (Cdk8) acts with the Mediator complex to regulate RNA polymerase II-meditated transcription. While its role in transcription has been well established in different model organisms, there is limited information about its potential Mediator-independent functions. We find that when Cdk8 is knocked down ubiquitously in Drosophila, it causes defects in flight and climbing ability, as well as reduced lifespan. These phenotypes are found in flies mutant for either Pink1 (PTEN-induced putative kinase 1) or Parkin in Drosophila models of Parkinson’s Disease. Pink1 and Parkin act in quality control of mitochondria. pink1 loss of function leads to the accumulation of damaged mitochondria. We find that ectopic expression of Cdk8 can significantly rescue pink1 mutant phenotypes, including locomotor impairment and defects in mitochondrial morphology and integrity. Furthermore, we show that Cdk8 and its partner CycC regulate mitochondrial morphology under physiological conditions.
Friday, March 26th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Ulrich Tepass (u.tepass@utoronto.ca)
CSB Seminar: The last step is the hardest: Lignin and suberin formation in the cell wall
“The last step is the hardest: Lignin and suberin formation in the cell wall”
Niko Geldner, Full Professor
University of Lausanne
Abstract:
Lignin and suberin are omnipresent polymers, used by humans since the dawn of civilisation. They are the defining components of wood and cork, but the occurence and importance of these two polymers is much more widespread and diverse. This is especially evident for the overall little amount of lignin and suberin deposited in the root endodermis, where absence of lignified Casparian strips or suberised secondary cell walls has a profound impact on root permeability and stress resistance. Beyond its direct physiological importance, the endodermis is therefore an interesting model system to study the cell biology of lignification and suberisation. A protracted problem in lignin and suberin research have been the crucial last steps of monomer delivery to, and polymerisation within, the cell wall. Here, I will report on high-order CRISPR/Cas9-induced mutants of suberin and lignin biosynthetic enzymes, providing strong evidence for the function of GDSL lipase and peroxidases in suberin and lignin polymerisation, respectively. I will also describe overlooked subcellular structures that are strongly associated with suberin deposition in the endodermis and could be involved in delivery of suberin precursor to the cell walls.
Friday, March 12th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Student invited speaker (Natalie Hoffmann and Eduardo Ramirez Rodriguez)
CSB Seminar: Emergent cellular ecosystems in melanoma revealed by single cell analysis
“Emergent cellular ecosystems in melanoma revealed by single cell analysis”
Arjun Raj, Full Professor
University of Pennsylvania
Department of Bioengineering
Department of Genetics
Abstract:
Anti-cancer therapies can often kill the vast majority of tumor cells but a few rare cells remain and grow despite treatment. Non-genetic variability has emerged as a potential contributor to this behavior. However, it remains unclear what drives this variability, and what the ultimate phenotypic consequences are. We have developed a set of new single cell barcoding technologies (Rewind and FateMap) that have enabled us to show how different types of variability can translate into different drug-resistant outcomes upon treatment with drug. In particular, we found that even a genetically and epigenetically clonal population harbors enough latent variability to produce an entire ecosystem of different resistant cell types, and show preliminary evidence suggesting that these cell types can contribute to tumor development in distinct ways.
Friday, 12th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Student invited speaker (Steven Chen)