CSBGU and Post-Doc Seminars: Alex Sin (Harrison Lab) and Aaron Sin (Sokolowski Lab)
CSBGU and Post-Doc Seminars
Alex Sin (Harrison lab)
"Does the Mammalian Golgi Complex Grow? A Quantitative Analysis of Golgi Size Changes during Interphase"
Aaron Allen (Sokolowski lab)
"Deciphering Pleiotropic Effects in Energy Homeostasis"
Please join us for talks and pizza lunch in RW 432
CSB Graduate Seminar Series Organizing Committee
Jennifer Doucet, Benjamin Scott, Junior West, Yixie Zhang, Donghoon Lee
Prof. David Graves, Chemical and Biomolecular Engineering, University of California at Berkeley
"Cold Atmospheric Plasma Biomedicine"
Abstract:
Ionized gas plasmas near room temperature are used in a remarkable number of technological applications mainly because they are extraordinarily efficient at exploiting electrical power for useful chemical and material transformations near room temperature. For example, plasma-assisted thin film deposition and etching applications in integrated circuit manufacture have evolved into technologies that allow control of features at the nanometer scale in commercial processes.
In this seminar, I will address the newest area of low temperature ionized gas plasmas, in this case operating under atmospheric pressure conditions, in which the temperature-sensitive material is living tissue. We sometimes use the term cold atmospheric plasma (CAP) to describe near-room temperature, atmospheric pressure partially ionized gas plasmas.
CAP research directed towards biomedical applications such as sterilization, surgery, wound healing and anti-cancer therapy has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that CAP readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ‘redox’ (or oxidation-reduction) biology. I will review the evidence suggesting that RONS generated by plasmas are responsible for their observed therapeutic effects.
Finally, I will review recent research results from our group and from other groups around the world, and suggest some of the more promising intellectual challenges and biomedical applications from our current perspective.
Host: Prof. Maurice Ringuette
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Departmental Seminar Prof. Cheryl Arrowsmith The Structual Genomics Consortium, Princess Margaret Cancer Centre Dept of Medical Biophysics, U of T
"Open Access Chemical Probes of Chromatin Regulators"
Abstract:
Regulation of gene expression via chromatin associated factors and alterations of the cellular epigenome are fundamental to most biological processes, and many disease mechanism. We are taking a protein family approach to understand how chromatin regulatory proteins recognize specific histone tail sequences and their posttranslational modifications. Proteins such as histone methyltransferases, demethylases, acetyltransferases and bromodomains and chromodomains mediate nuclear signaling networks that regulate epigenetic cellular states and gene expression programs. Systematic structural and biochemical analyses of these protein families are revealing key features of selectivity and regulation among these factors, enabling structure-based development of potent, selective, cell-active small molecule inhibitors of individual epigenetic regulatory proteins. Such compounds – Chemical Probes - are extremely valuable for understanding epigenetic signaling mechanisms in cells. Chemical probes are highly complementary to genetic methods and more closely mimic strategies for therapeutic translation. We are providing our epigenetic chemical probes as an open access resource to the biological research community to facilitate understanding of epigenetic mechanisms and to more rapidly identify and validate therapeutic targets for cancer and other diseases.
Host: Prof. Peter McCourt
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Seminar: Prof. Michael Wilson, The Hospital for Sick Children, Dept of Molecular Genetics, University of Toronto
CSB Departmental Seminar
Hospital for Sick Children
Dept of Molecular Genetics
University of Toronto
"Understanding the Human Regulatory Genome with Comparative Genomics"
Abstract:
As exon-based disease gene sequencing strategies give way to whole genome sequencing, the need to interpret the functional relevance of gene regulatory regions will become increasingly important. To test whether evolutionary conservation of combinatorial protein-DNA interactions gives insight into human gene regulatory function, we experimentally determined transcription factor (TF) binding locations of four liver-essential TFs (HNF4A, CEBPA, ONECUT1, and FOXA1) in liver tissue from five species. Indicative of the functional relevance of conserved combinatorial TF binding events, we discover conserved CRMs in the promoters of multiple genes involved in blood coagulation and lipid metabolism pathways that have repeatedly suffered rare, disease causing mutations. I will discuss our ongoing work that suggests that multi-species analyses of experimentally determined combinatorial TF binding will be useful in identifying gene regulatory regions critical for tissue-specific gene control.
Host: Prof. Jennifer Mitchell
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Seminar: Prof. Sergey Plotnikov, Cell & Systems Biology, University of Toronto
CSB Departmental Seminar
Prof. Sergey Plotnikov
Cell and Systems Biology
University of Toronto
"Integration of Two Distinct Actin Networks by Focal Adhesions Mediates Cellular Mechanosensing"
Abstract:
Eukaryotic cells sense the mechanical properties of their microenvironment to control a wide variety of physiological functions, including cell survival, proliferation, differentiation, and migration. Recently, much emphasis has been placed on understanding the molecular mechanisms of cell mechanosensing via integrin-based focal adhesions. However, how the actin cytoskeleton, a dynamic network that generates mechanical tension and transmits it to the focal adhesions, contributes to cell mechanosensing remains largely unknown. By combining live-cell imaging, pharmacological perturbations and mathematical modeling, we deciphered the contribution of two functionally distinct actin-based domains, branched actin network and stress fibers, in mechanosensing. We further identified a specific negative feedback between formin-mediated stress fiber elongation and actomyosin contractility that drives dynamics of traction force in focal adhesions and determines range of ECM stiffness sensed by a cell. These findings demonstrate that both lamellipodia and lamellar actin networks mechanically integrated by focal adhesions are critical for mechanosensitive cellular response.
Host: Prof. Maurice Ringuette
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Seminar: Prof. Jean Gariepy, Depts of Pharmaceutical Sciences and Medical Biophysics
CSB Departmental Seminar
Prof. Jean Gariepy
Depts of Pharmaceutical Sciences and Medical Biophysics
University of Toronto
SRI Research Chair in Biomolecular Engineering
Sunnybrook Research Institute
"Functional Aptamers, a New Class of Biotherapeutics"
Abstract:
Aptamers are short, synthetic single strand oligonucleotides that bind specifically and selectively to a given target. Aptamers are derived by an in vitro, PCR-based iterative process known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Our group has recently generated DNA aptamers that bind to well known druggable targets. Importantly, agonistic and antagonistic aptamers to these targets were identified using functional assays making them valuable as potential biotherapeutics. The concept behind aptamer searches and examples of derived aptamers with potent in vitro and in vivo activities will be discussed in this presentation.
Host: Prof. Maurice Ringuette
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Seminar: Prof. Jeffrey F. Harper, Dept of Biochemistry, University of Nevada, Reno
CSB Departmental Seminar
Prof. Jeffrey F. Harper
Chair of Department of Biochemistry
University of Nevada, Reno
"Coding and Decoding Calcium Signals in Plants"
Abstract:
Research in the Harper lab is focused on the role of Ca2+ signalling in various aspects of plant biology, including pollen tube growth and fertilization, and regulation of biotic and abiotic stress responses. Projects include understanding the structure and biological functions of proteins that both create and decode Ca2+ transients. For example, ion channels such as CNGCs (Cyclic Nucleotide-Gated Ca2+-permeable ion Channels) and Ca2+ pumps such as the ACAs (Autoinhibited Ca-ATPases). These pumps and channels form circuits that are regulated to control the influx and efflux of Ca2+ into the cytosol (i.e., Ca2+ transients). In addition, the lab is interested in how different Ca2+ transients are decoded through the activation of CPKs (Calcium-Dependent Protein Kinases) and how these phospho-regulatory pathways are used to control processes important for growth, such as secretion and cell wall biosynthesis.
Host: Prof. Keiko Yoshioka
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Seminar: Prof. John Parkinson, Hospital for Sick Children, Biochemistry & Molecular, University of Toronto
CSB Departmental Seminar
Prof. John Parkinson
Hospital for Sick Children
Biochemistry & Molecular and Medical Genetics
University of Toronto
"Evolution of Symbioses: Understanding the Impact of Genetic Diversity through a Systems Perspective"
Abstract:
Single celled, apicomplexan parasites such as Plasmodium, Toxoplasma and Cryptosporidium cause devastation and misery to millions worldwide. Despite their significance, few effective treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. Our group’s research focuses on combining genomics with systems based methods to understand how genetic diversity contributes to parasite survival strategies and virulence. For example, we showed how strain variants of the coccidian parasite, Toxoplasma gondii, alter their metabolic capacity to affect growth and virulence potential and consequently exhibit differential susceptibilities to drug inhibition; findings with obvious implications for the design of global intervention strategies.
In more recent work, we sequenced the genome of Sarcocystis neurona, a tissue-cyst forming member of the Coccidia and close relative of T. gondii, that is arguably the most successful single celled parasite genus in the world. Genome comparisons across the clade, including Eimeria, Neospora and Toxoplasma identified a variety of molecular innovations that have helped drive the transition from a purely enteric parasite dependent on a single host (Eimeria), to those able to invade the tissues of multiple intermediate hosts (Sarcocystis, Toxoplasma and Neospora). Through the identification of pathways that can be targeted for therapeutic intervention, these studies are laying the foundation for future drug development strategies.
Host: Prof. Maurice Ringuette
Video Conferencing at UTM (DV 4001) & UTSc (MW 229)
CSB Seminar: Dr. Ann Dean, National Institutes of Health, Bethesda, Maryland
CSB Departmental Seminar
Dr. Ann Dean
Laboratory of Cellular and Developmental Biology
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health, Bethesda, Maryland
“LDB1 Contributions to Enhancer Chromatin Looping and Erythroid Gene Activation”
Abstract:
Distal enhancers control cell-specific transcriptomes through contacting target genes. Interactions between lineage specific activators bound to enhancers and target promoters can account for the cell-type specificity of gene activation. One example is the dimerization of LDB1 bound at the b-globin LCR and gene promoter as part of an erythroid complex including GATA1, LMO2 and TAL1. The dimerization domain of LDB1 is both necessary and sufficient to mediate this chromatin looping. Moreover, the LDB1 dimerization domain provides a transcription activating function through which it is required for recruitment of RNA pol II to a looped b-globin locus. Genome-wide mapping in murine primary hematopoietic cells revealed a large cohort of erythroid genes regulated by LDB1, suggesting it can function broadly to affect lineage commitment, potentially through enhancer looping. However, only about 15% of erythroid genes have promoters bound by the LDB1 complex. We identified a subset of erythroid genes with CTCF-bound promoters that interact with LDB1-bound known or putative enhancers. LDB1 and CTCF interact directly to mediate enhancer-gene contact. CRISPR-Cas9 deletion of select enhancers compromises gene transcription, validating enhancer function and generalizing the contribution of LDB1-CTCF interaction to enhancer looping. Thus, in addition to self-interaction, LDB1 can co-opt CTCF into cell type specific enhancer looping interactions to specify an erythroid transcriptome.
Host: Jennifer Mitchell
CSB Seminar: Prof. Zhonglin Mou, Microbiology and Cell Science, University of Florida
CSB Departmental Seminar
Prof. Zhonglin Mou
Microbiology and Cell Science
University of Florida
“Function of Extracellular NAD(P) in Plant Immunity”
Abstract:
Emerging evidence from research in mammalian cells has indicated that cellular NAD(P) can be actively or passively released into the extracellular compartment (ECC), where NAD(P) is processed or perceived by ectoenzymes or cell-surface receptors/channels, leading to transmembrane signaling. Surprisingly, no homologous proteins of mammalian ectoenzymes have been identified in plants, which calls into question whether extracellular NAD(P) [eNAD(P)] and eNAD(P)-activated signaling pathways exist in plants. We found that exogenous application of NAD(P) induces immune responses without changing intracellular NAD(P) homeostasis in Arabidopsis, suggesting that NAD(P) may function in the ECC of plant cells. Moreover, during pathogen infection, cellular NAD(P) is released into the ECC and the amount of NAD(P) released is sufficient for activating immune responses in Arabidopsis. These data suggest that eNAD(P) may act as an endogenous elicitor in plant immune response. Supporting this hypothesis, the well-characterized human NAD(P)-metabolizing ectoenzyme CD38, when expressed in Arabidopsis, suppresses eNAD+-induced defense gene expression and disease resistance, indicating that the mechanisms used by plants to process or perceive eNAD(P) for immune response activation may not be the same as those in mammalian cells. Presently eNAD(P)-activated signaling networks in plants remain undefined and how eNAD(P) is processed or perceived by plant cells is unknown. We are addressing these questions through microarray and genetic experiments. Results of these experiments and possible plant cell-surface targets/receptors of eNAD(P) will be discussed.
Host: Keiko Yoshioka