Dr Molly Shoichet, PhD, O.C., O. Ont., FRS
Crédits photo: Brigitte Lacombe
Professor Molly Shoichet is University Professor, a distinction held by less than 2% of the faculty, at the University of Toronto. She served as Ontario’s first Chief Scientist in 2018 where she worked to enhance the culture of science. Dr. Shoichet has published over 650 papers, patents and abstracts and has given over 420 lectures worldwide. She currently leads a laboratory of 30 and has graduated 220 researchers. Her research is focused on drug and cell delivery strategies in the central nervous system (brain, spinal cord, retina) and 3D hydrogel culture systems to model cancer. Dr. Shoichet co-founded four spin-off companies, is actively engaged in translational research and science outreach. Dr. Shoichet is the recipient of many prestigious distinctions and the only person to be inducted into all three of Canada’s National Academies of Science of the Royal Society of Canada, Engineering and Health Sciences. In 2018, Professor Shoichet was inducted as an Officer of the Order of Canada and in 2011, she was awarded the Order of Ontario. Dr. Shoichet was the L’Oreal-UNESCO For Women in Science Laureate for North America in 2015, elected Foreign Member of the US National Academy of Engineering in 2016, won the Killam Prize in Engineering in 2017 and elected to the Royal Society (UK) in 2019. In 2020, Dr. Shoichet was awarded the NSERC Herzberg Gold Medal and won the Margolese National Brain Disorders Prize. Dr. Shoichet received her SB from the Massachusetts Institute of Technology (1987) and her PhD from the University of Massachusetts, Amherst in Polymer Science and Engineering (1992).
Overcoming Barriers: Re-engineering the Enzyme Chondroitinase ABC for Slow Release in the Central Nervous System
University Professor and Michael E. Charles Chair in Chemical Engineering,
Associate Chair, Graduate Studies
Chemical Engineering & Applied Chemistry
Donnelly Centre
University of Toronto
160 College Street – room 514
Toronto, ON M5S 3E1
416 978 1460
molly.shoichet@utoronto.ca
https://shoichetlab.utoronto.ca/
@ShoichetLab
Dr Matthew Harrington
Matthew Harrington is Associate Professor and Canada Research Chair Tier 2 in Green Chemistry in the Department of Chemistry at McGill University, as well as co-director of the McGill Institute of Advanced Materials (MIAM). He received his Ph.D. in 2008 from the University of California, Santa Barbara in the lab of J. Herbert Waite. This was followed by a Humboldt postdoctoral fellowship at the Max Planck Institute of Colloids and Interfaces in the Department of Biomaterials, where he was later a research group leader from 2010 until 2017. His research is focused on understanding biochemical structure–property relationships in the function and formation of biological materials and applying extracted design principles for the development and sustainable production of bio-inspired materials.
Biological fabrication of hierarchical materials from protein condensate
Nature provides an excellent role model for inspiring sustainable production of high-performance polymeric materials. For example, mussels rapidly fabricate hierarchically structured biopolymeric fibers known as byssal threads, which have emerged as an important source of bio-inspiration due to their remarkable material properties (e.g. high toughness, self-healing, wet adhesion). Understanding the physical and chemical principles underlying byssal thread production may inspire greener materials fabrication in the future; however, currently, the principles governing this process are poorly understood.
Byssal threads are produced via bottom-up self-assembly of over 15 different protein building blocks, which localize in specific regions of the fiber with nanoscale precision. Our group has harnessed advanced material characterization techniques, including confocal Raman spectroscopy, X-ray fluorescence microscopy and focused ion beam scanning electron microscopy (FIB-SEM), coupled with traditional biochemical approaches to investigate this process. We have discovered that mussels employ condensed fluid protein phases (e.g. coacervates, liquid crystals) as precursors for byssus assembly. These dynamic phases enable the pre-organization of protein building blocks, which respond to specific chemical and physical triggers (pH, redox potential, ion content, mechanical shear) to initiate the “fluid-to-fiber” transformation. Protein condensates are secreted into a network of channels resembling a microfluidic device, where they undergo liquid-liquid phase separation (LLPS) and are simultaneously cross-linked via coordination complexation with co-secreted metal ions (Fe, V, Zn). Extracted design principles hold direct relevance for inspiring production of advanced polymer materials and adhesives.
M. Joanne Lemieux, Professor, University of Alberta
Dr. Joanne Lemieux obtained her BSc, and MSc at Dalhousie University (Canada), and her PhD at New York University (USA), where she determined the structure of a gradient-driven transporter, published in Science 2003. In her postdoctoral fellow position, she focused on crystallization of membrane proteases and solved structures of the rhomboid protease family (PNAS 2007). In 2007 was hired as an Assistant Professor at the University of Alberta. She is currently a Full Professor in the Department of Biochemistry at the University of Alberta. She is also the Director of the Membrane Protein Disease Research Group. She leads a diverse research program to utilizes X-ray crystallography to gain insight into structure of membrane transporters, membrane proteases, optogenetic sensors. More recently her research is focused on the development of antivirals that target coronavirus proteases to treat COVID19.
Structural studies towards the development of an oral protease inhibitor to treat SARS-CoV-2 infection
Despite progress in vaccine development, antivirals targeting SARS-Co-2 are needed to help combat infection in regions where vaccines are not available or for those who are immunocompromised. Proteases cleave peptide bonds of a very specific sequence making them strong drug targets. Antivirals that target proteases are already used clinically to treat HIV and Hepatitis C virus. We have developed inhibitors of the SARS-CoV-2 protease to prevent the main protease from cleaving the viral polypeptide and subsequent viral replication in cells. Early studies focuses on the re-purposing of the feline coronavirus protease inhibitor, GC376. X-ray crystallography revealed the mechanism of inhibition, and has helped the optimisation of new derivatives. During optimisation, new derivatives were designed and variations were made with both the warhead region and subsite-binding region of the compounds. Our lead compounds have low nanomolar IC50 values and submicromolar EC50 values. Moving forward, these inhibitors will be tested with variant proteases, followed up by pre-clinical studies in animals to determine efficacy and pharmacokinetics in preparation for clinical trials.
Nobuhiko Tokuriki
Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
E-mail: tokuriki@msl.ubc.ca
Exploring evolutionary dynamics and phenotypic diversity of antibiotic resistance genes.
The wealth of enzyme functions found in nature is impressive. The on‐going evolutionary divergence of enzymatic functions continues to generate new and efficient catalysts, which can be seen through the emergence of antibiotic resistance genes among pathogens. While this arms-race between our development of novel antibiotics and the emergence of antibiotic resistance genes is devastating, we can learn much from its dynamics and may be able to develop strategies to evade and control the evolution of antibiotic resistance genes. Such knowledge is also important for understanding general principles of protein evolution, which has helped us to develop new protein engineering strategies.
In this talk, I will present our recent and on-going studies on understanding the evolutionary dynamics of beta-lactamases, one of the major sources of multi-drug resistance genes in pathogens. First, I discuss about the comprehensive protein bioinformatics to unveil the origins of six different beta-lactamase families and existence of massive beta-lactamase genes in environments. Second, I will present how phenotypes and evolvability are different among homologous enzymes within a beta-lactamase family. Third, I will show our efforts to explore high-resolution mutational mapping of metal-beta-lactamases using deep mutational scanning and experimental evolution. I will discuss how phenotypic diversity can arise and the importance of phenotypic diversity in protein evolution and engineering.
Courte biographie du professeur Nobuhiko Tokuriki
2004 : PhD Osaka University (Japan)
2004-2009: Posdoc Weizmann Institute of Science (Israel)
2009-2011: Posdoc University of Cambridge (UK)
2011-2017: Assistant professor, Michael Smith Laboratories, UBC
2017- : Associate professor, Michael Smith Laboratories, UBC
Lewis E. Kay
Lewis Kay is Professor of Molecular Genetics, Biochemistry, and Chemistry at the University of Toronto and a Senior Scientist at the Hospital for Sick Children. He received his B.Sc. in Biochemistry from the University of Alberta in 1983 and his Ph.D. in Biophysics from Yale University in 1988, pursuant to which he spent three years as a postdoctoral fellow in Chemical Physics at the NIH.
Prior to Professor Kay’s appointment at the University of Toronto he was Scholar in Residence from 1991-1992 at Kingston’s minimum security prison. During this time of personal growth and reflection Professor Kay took it upon himself to educate other inmates on the beauty of quantum mechanics. Remarkably, three of the inmates who received instruction are now on faculty at the University of Toronto and are involved in senior administration.
Professor Kay’s research cuts across the interface of physical chemistry and medical sciences. His work focuses on transforming the techniques of nuclear magnetic resonance (NMR) spectroscopy as applied to the study of large proteins and their complexes, in particular those that are involved in health and disease.
Professor Kay is a Fellow of both the Royal Society of London and the Royal Society of Canada as well as an International Member of the National Academy of Sciences.
The important role of dynamics in the function and misfunction of molecular machines
Protein molecules play critical roles in cellular function and they catalyze many of the biochemical reactions that are necessary for life. The three-dimensional shapes of these molecules are crucial for guiding proper function and they can change with time due to interactions with other molecules, various stresses on the cell or simply the result of random fluctuations. Although very detailed static pictures of protein molecules have been produced using traditional biophysical tools, macromolecular function and misfunction is, in many cases, intimately coupled to flexibility and knowledge of molecular motions therefore becomes critical. For the past 3 decades my laboratory has developed biophysical techniques, focusing on solution based Nuclear Magnetic Resonance spectroscopy for the study of biomolecular dynamics. A brief description of some of the methods we have derived will be given along with examples to illustrate the critical importance of dynamics to protein function and misfunction.
