CSB Special Seminar: Dr. Ivan Shabalin, Dept of Molecular Physiology & Biological Physics, University of Virginia, Charlottesville, VA
Cell & Systems Biology
Special Seminar
Dr. Ivan Shabalin
Research Scientist
Dept of Molecular Physiology & Biological Physics
University of Virginia
Charlottesville, VA
"Transformation of High-Throughput Protein Crystallization Screening into High-Output"
Abstract:
Many protein crystallization methods and tools have been developed over the past decades. Among them are many commercially available screens and numerous protein modification methods for improvement of protein “crystallizability,” such as affinity tag removal/retention, methylation, surface mutagenesis and limited proteolysis. Given the options, choosing an effective crystallization strategy can be a daunting task, especially if the supply of protein is limited and protein production is expensive. In addition, many of those methods are relatively time-consuming, and require significant amounts of consumables. The use of the LabDB/XtalDB database system allowed us to systematically study the crystallization of a large number of protein targets and perform comparative analysis of different methods and approaches. In our recent work on a set of 97 NYSGRC targets, we used various techniques to develop an optimized strategy for protein crystallization, which resulted in the determination of the structures of 42 targets (a 43% success rate). The study was guided by multiple goals—maximizing the number of successful crystallizations, yet limiting the resources necessary for screening and optimization by including tests of some less popular, yet promising, techniques. The methods we used included initial screening with alternative reservoirs, limited proteolysis in situ, co-crystallization with function-based potential ligands, “air-dry” cryoprotection of crystals, and many others. Based on our experience, we suggest an easy-to-follow protein crystallization strategy, which is cost- and time-effective but has proved to be high-output rather than high-throughput.
If time permits, he will also discuss a second topic: Reliability of protein crystal structures for structure-based drug discovery.
CSBGU Seminar: Dr. Mehrdad Hariri, CEO & President of the Canadian Science Policy Centre
CSBGU and Departmental Seminar
Dr. Mehrdad Hariri
CEO & President of the Canadian Science Policy Centre
"Status of Science in Canada, New Frontiers of Science in Society"
Friday April 29, 2016 at 3:30-4:30pm
Ramsay Wright Building, Rm 432
Host: Cell and Systems Biology Graduate Union (CSBGU)
Abstract:
In this presentation Mehrdad Hariri will discuss the status of the science enterprise in Canada, especially in comparison with other nations. He will then address the new frontiers of science in society in the 21st century, along with the opportunities and challenges the scientific community is facing in these new frontiers.
The ever-changing nature of science, along with transformative technological advances and significant changes in societies around the world have all affected the nature of the interaction between science and society. Science today impacts every aspect of our society including the economy, public policy and politics, international affairs, social innovation, communications and more. How does science relate to politics and politicians? How does science relate to public policy, and what is the role of scientists in designing policies? Does science have any role in international affairs and diplomacy? How is science being communicated to various sectors of society, including the public at large?
The scientific community needs to be better prepared for the new frontiers that are transforming how science interacts with society. It is the younger generation of scientists that will play a crucial role in adapting to these changes. Are Canadian institutions ready for this transformation and have we built training capacities for the next generation to take on this role? What career opportunities exist for our students to contribute to this effort? These are some of the questions that Mehrdad Hariri will explore in his presentation.
Background information on Dr. Hariri:
Mehrdad Hariri is the founder and CEO of the Canadian Science Policy Centre, a not-profit virtual HUB for science technology and innovation policy in Canada. He founded the national annual Canadian Science Policy Conference (CSPC), a national multidisciplinary forum dedicated to the Canadian Science Technology and Innovation (STI) Policy discussions, engaging hundreds of organizations from various sectors and across the country to discuss the most pressing issues in Canadian Science and Innovation Policy. Dr. Hariri has numerous publications and opinion pieces in various media outlets, and regularly appears in media as a commentator on science policy issues. He studied in the fields of Veterinary Medicine, Cell Biology and Functional Genomes, in Tehran, Montréal, and Toronto universities, and performed a post-doctoral research fellowship at the McLaughlin-Rotman Centre for Global Health.
Please go to the following website for more information: www.sciencepolicy.ca
CSB Seminar: Dr. Karim Mekhail, Laboratory Medicine and Pathobiology (LMP), University of Toronto
CSB Departmental Seminar
Dr. Karim Mekhail
Laboratory Medicine and Pathobiology (LMP)
University of Toronto
"Genome Stability: From Molecular DNA Ambulances to Destructive RNA-DNA Marriages"
Host: Prof. Jennifer Mitchell
Refreshments will be served. All are welcome!
Video Conferencing at UTM (DV 3138) & UTSc (MW 229)
Abstract:
Two lines of investigation will be covered in this talk. First, I will present how we used a combination of systems biology, genetic and molecular biology tools in yeast to identify the first molecular DNA ambulance. This line of work revealed a conserved role for motor proteins in the transport of damaged DNA for repair. Similar roles for motor proteins in mediating DNA repair have since been observed in mammals. Second, I will discuss how we have used a combination of yeast and human systems to uncover a role for the ATXN2 gene, which is mutated in amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2), two highly debilitating and too often lethal neurodegenerative diseases. Our findings reveal a conserved role for ATXN2 in the suppression of genome destabilizing RNA-DNA hybrids, or R-loops. This line of work also highlights a molecular mechanism that can unify many neurodegenerative disease-linked genes pointing to important targets for therapeutic development. Overall, these two lines of work reveal exquisite and conserved mechanisms maintaining genome stability and show how such processes are compromised in various human diseases pointing to novel therapeutic avenues.
CSB Seminar: Dr. John Hammer, Molecular Cell Biology Section, National Institutes of Health
CSB Departmental Seminar
Dr. John Hammer
Molecular Cell Biology Section
National Institutes of Health
Bethesda, MD
"Revealing the Secrets of T Cell Immunological Synapse Formation and Function using Super Resolution Imaging"
Host: Prof. Sergey Plotnikov
Refreshments will be served. All are welcome!
Video Conferencing at UTM (HSC 332) & UTSc (MW 229)
Abstract:
Upon antigen recognition, actin assembly and inward flow in the plane of the radially symmetric immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin LFA-1. Using two forms of structured-illumination microscopy (SIM), we have found that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the distal edge of the IS. After traversing the outer, Arp2/3-generated, lamellopodia-like region of the IS, these linear filaments are organized by myosin II into concentric arcs that should possess the anti-parallel organization required for contraction. Quantitative, fixed-cell 3D-SIM shows that open, active LFA-1 often aligns with arcs while TCR MCs commonly reside between arcs, and live-cell TIRF-SIM shows TCR MCs being swept inward by arcs. Consistently, disrupting actin arc formation via formin inhibition results in less centralized TCR MCs, miss-segregated integrin clusters, decreased T: B cell adhesion frequency, and diminished proximal TCR signaling. Together, our results define the origin, organization, and functional significance of a major actomyosin contractile structure at the IS that directly propels TCR MC transport.
CSB Seminar: Prof. Jacqueline Monaghan, Biology Department, Queen's University
CSB Departmental Seminar
Prof. Jacqueline Monaghan
Biology Department
Queen’s University, Kingston
"Mechanisms Regulating Plant Immune Homeostasis"
Host: Prof. Nicholas Provart
Refreshments will be served. All are welcome!
Abstract:
Plants have evolved a multi-faceted immune system to fight against pathogen infection. While necessary for survival, pathogen perception and the activation of immune responses are energetically taxing for the host and have been linked to considerable fitness costs. Although defense signaling pathways must therefore be tightly regulated, very little is known about the biochemical mechanisms that tailor signaling to maintain cellular homeostasis. My research focuses on understanding the regulatory mechanisms that allow plants to defend against a vast array of potential pathogens while maintaining normal growth and development. Using a forward-genetics approach in an immune-deficient background, I previously identified a number of new players involved in immune homeostasis. In this talk I will discuss some of these players and highlight some projects currently underway in my new lab at Queen’s.
CSB Special Seminar: Dr. Msatsugu Toyota, Department of Botany, University of Wisconsin-Madison
CSB Special Seminar
Dr. Msatsugu Toyota
JST PRESTO Researcher
Department of Botany
University of Wisconsin-Madison
“Wound-induced Rapid Systemic Calcium Signaling in Arabidopsis”
Host: Prof. Keiko Yoshioka
Abstract: Plants, unlike animals, do not have a nervous system, but they can rapidly perceive local environmental stresses (i.e., mechanical wounding and herbivore attack), propagate this information throughout the plant body and activate systemic responses. However, the molecular basis underlying such rapid sensory and systemic signal transduction remains unclear. Using genetically-encoded Ca2+ and glutamic acid (Glu) indicators, we have visualized the plant-wide spatial and temporal dynamics of cytosolic Ca2+ and apoplastic Glu in response to wounding stress in Arabidopsis. Mechanical wounding caused immediate Ca2+ and Glu increases in the wounded leaf and subsequently this Ca2+ increase was transmitted via the phloem to distant target leaves. In these target leaves, defense marker genes and jasmonic acid/jasmonoyl-isoleucine were highly up-regulated within 2 minutes of mechanical wounding. We also found that the GLUTAMETE RECEPTOR LIKE (GLR) family of Ca2+-permeable channels was required for the wound-induced Ca2+ transmission and extracellularly-applied Glu in a leaf could trigger the similar systemic Ca2+ transmission and resistance responses. These data suggest that the plant GLR is a sensor to monitor the apoplastic Glu levels, and when symplastic Glu is leaked out of wounded cells GLR rapidly creates the Ca2+ signal propagating throughout the entire plant and activates systemic resistance responses in distant organs.
CSB Deptl Seminar: Dr. Timothy Mosca, Stanford University, Dept of Biology, Lab of Prof. Liqun Luo
CSB Departmental Seminar
Dr. Timothy Mosca
Stanford University
Department of Biology
Laboratory of Prof. Liqun Luo
“Molecular Mechanisms that Regulate Central Synapses in Drosophila”
Host: Prof. David Lovejoy
Refreshments will be served. All are welcome!
Video Conferencing at UTM (HSC 332) & UTSc (MW 229)
Abstract:
Modern neuroscience seeks to understand system-wide connectivity and whole-brain activity as determinants of the complex computations that underlie behavior, thought, and memory. Recent work, though, has revealed that knowledge of three-dimensional synaptic organization is essential to interpret connectivity through the lens of activity and vice versa. To date, synaptic organization in the brain has been less understood due to a lack of techniques to understand the three-dimensional synaptic landscape of an intact circuit. To address this, we have developed light level methods for quantifying synaptic organization in identified classes of neurons in the intact Drosophila brain. I will demonstrate the application of our new methodology, first to understand the basic "rules" that a CNS circuit follows to organize, and second, to describe the essential roles for a number of molecules in enforcing such rules. One such family of molecules, the Teneurins, evolutionarily conserved cell surface proteins, have critical roles at multiple phases of synaptic development via different mechanisms. I will highlight and contrast those specific roles and detail recent work both into Teneurin mechanisms and additional synaptic organizers working in the same system as the Teneurins to ensure proper synaptic organization and development.
CSB Deptl Seminar: Prof. David Lovejoy, Cell & Systems Biology, University of Toronto
CSB Departmental Seminar
Prof. David Lovejoy
Cell & Systems Biology
University of Toronto
"Adhesion G-protein Coupled Receptors: The Origin of
the Regulation of Stress-associated Metabolism in the Metazoa"
Host: Prof. Maurice Ringuette
Refreshments will be served. All are welcome!
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
Abstract:
The teneurin-ADGRL (latrophilin) pairing is the only trans-synaptic adhesion system that is conserved between invertebrates and vertebrates. Both the teneurin ligand and ADGRL receptor ligand was the result of lateral gene transfer from prokaryotes to an early eukaryotic ancestor of metazoans. Through subsequent gene duplications both systems radiated throughout the Metazoa. At the distal extracellular tip of the teneurins lies a bioactive peptide termed the “teneurin C-terminal associated peptide” (TCAP). Evidence indicates that TCAP was once the payload of a prokaryotic polymorphic proteinaceous toxin but has evolved to become a progenitor of metabolic peptides in vertebrates.
CSB Deptl Seminar: Prof. Vito Mennella, Dept of Biochemistry, University of Toronto
CSB Departmental Seminar
Prof. Vito Mennella
Dept of Biochemistry, University of Toronto
Cell Biology Program, The Hospital for Sick Children
"Supramolecular Assembly of the Centrosome"
Host: Prof. Maurice Ringuette
Refreshments will be served. All are welcome!
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
Abstract:
The centrosome is an organelle essential for human health: alterations of centrosome structure and function are responsible for neurodevelopmental disorders such as primary microcephaly and ciliopathies and for cancer progression. The centrosome plays a critical role in determining these disease states because it functions as the major microtubule-organizing center of the cell controlling the location and timing of microtubule nucleation, thereby ensuring accurate chromosome segregation, cilia formation and cell differentiation. To finely control microtubule organization, centrosomes form the Pericentriolar Material. This “supramolecular” assembly –a complex structure composed of multiple protein complexes —has previously eluded analysis of its high-order organization, because of its size below the diffraction limit of light. In this presentation we discuss our recent findings on the molecular architecture of the pericentriolar material and present evidence of a novel mechanism of regulation of its assembly.
CSB Deptl Seminar: Prof. Olivia Wilkins, Dept of Plant Science, McGill University
CSB Departmental Seminar
Prof. Olivia Wilkins
Department of Plant Science
McGill University
"Integrative Analysis Reveals the Gene Regulatory Network of Rice Leaves in Response to Environmental Stress"
Host: Prof. Nick Provart
Refreshments will be served. All are welcome!
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
Abstract:
Global regulatory networks (GRNs) coordinate the timing and rate of gene expression in response to environmental and developmental signals, genome-wide. The interactions between protein transcription factors (TFs) with conserved regulatory elements in genomic DNA that comprise the GRNs, are regulated through a variety of post-transcriptional and post-translational mechanisms. Learning GRN from single data types (e.g. gene expression, proteomics) has severe limitations as GRNs integrate signals on many levels. My research aims to learn GRNs associated with the response of tropical Asian rice (Oryza sativa), to high temperatures and water deficit, two of the main stresses affecting growth and yield.
In model prokaryotic and eukaryotic systems, where much of the true architecture of many GRNs is known, methods that combined expression data and additional data types that define structure priors were able to infer more accurate regulatory networks that methods based on gene expression data alone. We therefore undertook to incorporate multiple genome scale measurements to construct a robust network prior and to learn our GRN. This approach not only overcomes some of the shortcomings implicit in transcriptome based network prediction (e.g. co-expression as a proxy for regulation), it also leverages a multi-factor experimental design, including controlled and agricultural field experiments, to increase the resolution of the inferred network.