Following the Rabbit into Chemical Space
Dr. Brian K. Shoichet, PhD University of California, San Francisco
Hosted by Dr. Molly Shoichet
Snacks & Refreshments Available
Zoom Link:
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Meeting ID: 860 8663 8773
Passcode: 484696
Abstract:
Structure-based docking can be used to screen compound libraries for novel ligands. Recently, docking libraries have expanded from three million “in-stock” to over four billion make-on-demand (“tangible”) molecules. Docking these new libraries versus the dopamine, melatonin, and s2 receptors have revealed novel scaffolds with nM and sub-nM potencies directly from the docking. I will discuss recent applications to the alpha2a-adrenergic, serotonin, and cannabinoid receptors, and the serotonin transporter, where in vivo active leads have been developed for analgesia, depression, and opioid withdrawal. Methods questions will also be considered: the effect of bias toward bio-like molecules in the virtual libraries, how and if docking score improves as the libraries grow, how number tested affects the quality of the experimental actives, and whether we have reached a plateau in the results we can expect from large library docking, or if bigger remains better.
Speaker Bio:
Brian Shoichet received a B.Sc. in Chemistry and a B.Sc. in History in 1985, from MIT. MIT appears to have no record of this. He received his Ph.D. for work with Tack Kuntz on molecular docking in 1991, from UCSF. Shoichet’s postdoctoral research was largely experimental, focusing on protein structure and stability with Brian Matthews at the Institute of Molecular Biology in Eugene, Oregon, as a Damon Runyon Fellow. Colleagues from Eugene have only sketchy memories of his time there. One recalls, “He seemed to travel a lot.” Matthews himself was unavailable for comment. Shoichet joined the faculty at Northwestern University in the Dept.of Molecular Pharmacology & Biological Chemistry as an Assistant Professor in 1996. No record of this Department’s existence can be found outside of one locked filing cabinet in Gene Silinsky’s office. Silinsky was unavailable for comment. In a fit of absent-mindedness, Shoichet was promoted to a tenured Associate Professor in 2002, only one year after his younger sister, Molly Shoichet, received tenure at the University of Toronto. Shoichet denies any sensitivity around this issue. Around that time he was recruited back to UCSF, where he is now a Professor in the Department of Pharmaceutical Chemistry. We confused him with Kevan Shokat, admits a member of the recruiting committee at UCSF. A charismatic speaker, he is recalled as giving ‘the best talk at the worst Keystone Conference I ever attended,’ by a senior NIH Program Officer. Research in the Shoichet Lab seeks to bring chemical reagents to biology, combining computational simulation and experiment. An unanticipated observation emerging from the theory/experiment cycle was the colloidal aggregation of organic molecules. This phenomenon has great effects in early and late drug discovery, and we continue to investigate it. More broadly, we adopt a protein-centric approach that seeks new ligands to complement protein structures. This involves new docking methods, model experimental systems to test them. Using a ligand-centric approach, we seek new targets for established drugs and reagents. Whereas this lacks the physical foundation of the structure-based research program, it returns to an older, pharmacological view of biological relationships, bringing to it a quantitative model. A focus for both approaches is ligand discovery against G Protein-Coupled Receptors (GPCRs).
Professor Larry Lessard
Department of Mechanical Engineering McGill University, Montréal
Hosted by Professor Elizabeth Edwards
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Abstract:
Professor Larry Lessard, from McGill University in Montreal, Canada, works in the research area of recycling of composite materials. He will present work on recent projects on the topic of recycling and sustainability. Furthermore, Professor Lessard is undergoing a round-the-world bike trip to help promote these ideas and to film a documentary film on the subject. Bike62 will be cycling around the world from July 2022 to August 2023, a journey that will cover over 22,000Km, visit around 20 countries, and speak at 30 universities to promote ways to rethink and reuse composite materials.
Follow Professor Lessard’s journey:
website: www.bike62.com |Instagram: ridebike.saveplanet |YouTube: Bike62
Dr. Johnna Temenoff
PhD Georgia Tech/Emory University
After rotator cuff tendon tear, marked degeneration of the attached muscle is apparent clinically, with both fibrous and fatty infiltration of the tissue. Our laboratory is working on delivery strategies for biologics, including proteins and cells, that might slow or reverse this degeneration. In particular, our laboratory has focused on “jump-starting” host regenerative processes through use of glycosaminoglycan (GAG)-based biomaterials for release of cytokines to promote the recruitment of pro-healing cell populations, such as proresolving macrophages, and mesenchymal stromal cells (MSCs), into the muscle. In other work, we have explored priming strategies for MSCs to alter their immunomodulatory properties as a means to reduce inflammation, such as that which occurs in muscle after rotator cuff tendon tear.
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Dr. Johnna S. Temenoff is the Carol Ann and David D. Flanagan Professor the Coulter Department of Biomedical Engineering at Georgia Tech/Emory University. She is also currently the Deputy Director of a NSF Engineering Research Center in Cell Manufacturing Technologies (CMaT). Scientifically, Dr. Temenoff is interested in tailoring the molecular interactions between glycosaminoglycans and proteins/cells for use in regenerative medicine applications. Her laboratory focuses primarily on promoting repair after injuries to the tissues of the shoulder, including cartilage, tendon, and muscle. Dr. Temenoff has been honored with several prestigious awards, such as the NSF CAREER Award, Arthritis Foundation Investigator Award and Society for Biomaterials (SFB) Clemson Award for Contributions to the Literature, and was named to the College of Fellows of the American Institute for Medical and Biological Engineers (AIMBE), as a Fellow of the Biomedical Engineering Society (BMES) and as a Fellow of Biomaterials Science and Engineering, International Union of Societies for Biomaterials Science and Engineering (IUSBSE). She has co-authored a highly successful introductory textbook – Biomaterials: The Intersection of Biology and Materials Science, by J.S. Temenoff and A.G. Mikos (now in a 2nd edition), for which Dr. Temenoff and Dr. Mikos were awarded the American Society for Engineering Education’s Meriam/Wiley Distinguished Author Award for best new engineering textbook.
Dr. Lonnie Shea
PhD University of Michigan
Vaccines are the initial immunotherapy by providing a means to activate an immune response to specific antigens to protect against disease. This success has motivated the development of alternative immunotherapies for treating undesired immune responses, such as those found in autoimmune disease, allergy, organ transplantation, and cancer, with the objective to attenuate responses. For autoimmune and allergic disease, we have developed nanoparticles loaded with antigen or allergen, which suppresses the antigen specific response without impacting the remainder of the immune system. The nanoparticles maintain the antigen until internalization by immune cells, with subsequent presentation of the antigen coincident with down-regulation of the co-stimulatory factors and up-regulation of negative co-stimulators. Similar nanoparticles have been applied to attenuate inflammation, such as that associated with cancer progression. A critical need for treating undesired immune responses is the identification of disease prior to significant tissue damage, with disease such as Type 1 Diabetes, multiple sclerosis, or metastatic cancer often detected through patients selfreporting symptoms. We have developed scaffold implants that support the formation of tissues that function as an immunological niche to represent the immune function in endogenous tissues. The early detection and treatment of undesired immune responses provides an opportunity to ameliorate disease while preserving tissue function.
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Lonnie Shea is the Steven A. Goldstein Collegiate Professor in the Department of Biomedical Engineering at the University of Michigan (U-M), which is joint between the College of Engineering and the School of Medicine. He received his PhD in chemical engineering and scientific computing from U-M in 1997, working with Professor Jennifer Linderman. He then served as a postdoctoral fellow with then Chemical Engineering Professor David Mooney in the Department of Biologic and Materials Science at the U-M Dental School. Shea was recruited to Northwestern University’s Department of Chemical and Biological Engineering and was on the faculty from 1999 to 2014. In 2014, Shea returned to the University of Michigan as chair of the Department of Biomedical Engineering, with his recruitment coinciding with the endowment of the chair position by William and Valerie Hall. His term as chair completed on June 30, 2021. He is the Steven A. Goldstein Collegiate Professor of Biomedical Engineering and is an internationally recognized researcher at the interface of regenerative medicine, drug and gene delivery, and immune-engineering, whose focus is on preventing tissue degeneration or promoting tissue regeneration. His projects include islet transplantation for diabetes therapies, nerve regeneration for treating paralysis, and diagnostics for immune dysfunction in cancer and autoimmunity. He is currently PI or co-PI on multiple NIH grants. Shea has published more than 270 manuscripts. He served as director of Northwestern’s NIH Biotechnology Training Grant. He has received the Clemson Award from the Society for Biomaterials, and also the recipient of their 2021 Technology Innovation and Development Award for his development of nanoparticles for tolerance in autoimmune disease. Shea is a fellow of the American Institute of Medical and Biological Engineering (AIMBE) and the Biomedical Engineering Society (BMES), a member of the editorial boards for multiple journals such as Molecular Therapy, Biotechnology and Bioengineering, and the Journal of Immunology and Regenerative Medicine.
Benjamin Sanchez-Lengeling
Research Scientist, Google Deepmind
Abstract:Properties of the physical world come to life through our human senses, digitizing these senses allows us to catalog, search and design percepts. We have made remarkable progress in the domain of vision, hearing, but what about the rest? Olfaction is a chemical sense, and in this talk, I will present our recently published work on how we built a digital representation of olfaction for single compounds, which we call the Primary Odor Map and can be used in a variety of olfactory tasks. To validate our representation, we selected a set of 400 novel and diverse molecules with no known recorded scent and had them rated by a panel of trained humans. We compared our predicted olfactory profiles with the panel consensus response and found that our machine learning model outperforms any single human in the panel. The story will touch on deep learning, molecular representations, compound discovery pipelines, training humans to reliably rate odor percepts, as well as diverse applications of a principal odor map.
Speaker Bio: Benjamin Sanchez-Lengeling is a researcher at Google DeepMind, solving chemical problems leveraging data-driven techniques. Ben designs, builds, and evaluates computational tools that enable molecular discoveries, covering small molecules, polymers, chemical mixtures, and proteins. Striving to bring computational predictions into the lab by designing experimental validation with collaborators, prioritizing the interpretation of our discoveries, and making research clear and approachable. Ben graduated with a Ph.D. in Chemistry and Chemical Biology and a secondary field in Computational Science & Engineering from Harvard University under the supervision of Alán Aspuru Guzik. Besides research, he is also passionate about science education and divulgation. He is one of thefounders and organizers of a STEM-education NGO Clubes de Ciencia Mexico and a LatinX-centered AI conference RIIAA.
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Simon Axelrod
PhD, Harvard University
Abstract:Light-activated drugs are a promising way to treat localized diseases for which existing treatments have severe side effects. However, their development is complicated by the set of photophysical and biological properties that must be simultaneously optimized. For example, photoactive drugs based on trans–cis isomerization must isomerize under light, absorb in the near-IR, have reasonably long cis lifetimes, and have differential cis–trans binding to a protein target. To accelerate the design of photoactive drugs, we develop new computational methods for predicting their properties. These techniques combine atomistic simulation with machine learning based on quantum chemistry. They enable the prediction of the isomerization efficiency, absorption spectrum, thermal half-life, and binding affinity. We use these tools to screen 5 million hypothetical ligands for the photoactive inhibition of the PARP1 cancer target. We identify several compounds with redshifted absorption spectra, ideal thermal half-lives, and differential protein binding under illumination. These results show that computation can help address the difficult optimization problem that is central to photoactive drug design.
Speaker Bio: Simon Axelrod received his BSc at Queen’s University in 2016, with a major in Physics. He received his MSc in Physics at the University of Toronto in 2017. He worked under Prof. Paul Brumer in the Chemistry department, developing theoretical models for understanding quantum effects in biology. He received his PhD in Chemical Physics from Harvard University in 2023. He worked under Prof. Eugene Shakhnovich (Chemistry) and Prof. Rafael Gomez-Bombarelli (Materials Science and Engineering, MIT), combining atomistic simulation with machine learning to accelerate drug discovery. In his spare time, Simon likes playing basketball, joking around with friends, and writing short bios.
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Benoit Lessard, University of Ottawa
Host: Prof. Tim Bender
Our society is faced with an increasing challenge of E-waste, and with the proliferation of the internet of things and smart packaging, this is only going to get worse. Low cost printed electronics are facilitating the development of emerging technologies, from artificial skin to stretchable and bendable cell phone displays. The desire to integrate these materials onto biodegradable substrates or to use compostable active materials is necessary. Furthermore, the chemical toolbox available to us enables the fine-tuning of the materials to design and engineer the desired properties. This seminar will cover our groups recent advances in the simple fabrication of semiconductive single walled carbon nanotube transistors on high performing green dielectrics, advances towards the development of biodegradable and flexible transparent heaters, and the use of phthalocyanines as low cost semiconductors for the development of point-of-source sensors such as cannabinoid detection and speciation. We aim to build structure property relationships between material design, thin film processing, and device performance for the enabling of sustainable next-generation electronics.
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Professor Benoit Lessard joined the Department of Chemical & Biological Engineering at the University of Ottawa in 2015 as an Assistant Professor, was promoted to Associate Professor in May 2019, and Cross Appointed to the School of Electrical Engineering and Computer Science in 2020. He was awarded the Tier 2 Canada Research Chair in Advanced Polymer Materials and Organic Electronics (renewed in 2020), 2018 Ontario Early Researcher Award, the 2015 Charles Polanyi Prize in Chemistry, The University of Ottawa Early Career Researcher of the Year Awards for 2021, the 2021 Chemical Engineering Innovation award (under 40), 2022 The Canadian Journal of Chemical Engineering Lectureship award and NOVA Chemicals MSED Early Career Investigator Award. Prof. Lessard was also named a 2018 J. Mater. Chem. C Emerging Researcher (RSC), Flexible and Printed Electronics Emerging Leaders of 2023 (IOPscience) and 2023 “Small” Nano Micro Rising Star (Wiley Journals).
Since 2008, Prof. Lessard has published 147 peer reviewed journal articles, 16 patent applications, and presented his work over 150 times at international and national conferences. Lessard is co-founder of Ekidna Sensing inc, a spinoff company based on cannabinoid sensors. Prior to joining uOttawa, Prof. Lessard completed an NSERC Banting Fellowship at the University of Toronto studying crystal engineering and OPV/OLED fabrication and obtained his PhD (2012) from McGill University in Polymer reaction engineering.
View the complete 2023-24 LLE schedule
Questions? Please contact Michael Martino, External Relations Liaison (michael.martino@utoronto.ca)
Professor Anne Kietzig
McGill University (Department of Chemical Engineering
Abstract: Functional surfaces in nature are often characterized by patterns of similar multi-length scale surface features of regular but random geometry. In science and engineering we prefer precise feature geometries that are accessible by mathematical formulations for kinetic and thermodynamic considerations. Femtosecond (fs) laser machining has emerged in the past decades as a versatile material processing technique which requires only one single process step to induce specific microfeatures that entail surface functionality. There is no limit to the material type that can be machined with lasers, however, the topological outcome is a direct response dictated by the respective material’s properties. Next to altering the surface topology of materials, laser irradiation also often causes changes in a surface’s chemistry, which upon understanding the underlying reaction mechanism can be exploited to tailor surface wetting and adhesion properties. This talk will provide an overview of our advances in exploiting laser-matter interactions to address various applications. Examples range from much discussed plant-leaf inspired non-wetting, to pitcher plant inspired directional and extreme wetting, shark skin-like drag reducing surfaces, easy flow surfaces and textured glass surfaces that change their opacity upon wetting like the “skeleton” flower, penguin-feather inspired ice-shedding and tailored adhesion of epoxy-metal bonds.
Speaker Bio: Anne Kietzig is a Professor at McGill University, Canada. She teaches and carries out research at the Department of Chemical Engineering and acts as Associate Dean for Student Affairs in the Faculty of Engineering. She started her undergraduate education of Chemical Engineering and Economy Studies at the Technical University of Berlin, Germany, where she graduated in 2006. She pursued her doctoral studies focused on microscopic ice friction at the Department of Biological and Chemical Engineering at the University of British Columbia in Vancouver, Canada. In 2010, she joined McGill as an Assistant Professor, where she leads a research program in Biomimetic Surface Engineering, which is built on two fundamental pillars: one being laser-material-interactions and the other being surface wetting. The fields of application are manifold and target tailoring optical properties, adhesion, drag, and friction on many materials.
Claudia Schmidt-Dannert, University of Minnesota
Host: Prof. Emma Master
In biological systems, simple building blocks such as proteins, nucleic acids and lipids are precisely organized to form higher ordered structures across multiple length scales. Harnessing the principles and mechanisms underlying the self-assembly and self-organization of natural structures and materials offers tremendous opportunities for the design and scalable fabrication of functional biomaterials with emergent properties. Proteins and peptides provide the greatest versatility for the bottom-up design and low-cost production of such self-assembling supramolecular materials due to the chemical diversity of their amino acid building blocks. They are also genetically encoded, allowing for the genetically programmable production of self-organizing materials using cell factories or synthesize self-assembling materials de novo via cell free expression systems. Proteins are also key players in the formation of inorganic-organic composite materials with properties unmatched by synthetic properties. Inspired by the spatial organization of enzymes at the subcellular level via protein nanostructures, we are taking advantage of these mechanisms for the design of self-assembling protein-based nano-architectures for different applications, including for in vitro biocatalysis and the fabrication of new types of functional materials. Of key interest to us is the discovery and design of mechanisms with which to interface protein-based materials with biomineralization processes to produce innovative materials with unique mechanical and other properties. I will discuss possibilities and examples from our work for the design of genetically encoded self-assembling 2D and 3D-protein scaffolds as functional materials for diverse applications, including for biocatalysis and biosynthesis and as living materials.
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Dr. Claudia Schmidt-Dannert is a Distinguished McKnight Professor and Kirkwood Chair of Biochemistry in the Dept. of Biochemistry and the Director of the Biotechnology Institute at the University of Minnesota.
She completed her B.S. and M.S. in Biochemistry and Genetics at the TU Braunschweig and performed her PhD research at the National Research Center for Biotechnology in Braunschweig (GBF, now Helmholtz Center for Infectious Diseases). She then moved to the University of Stuttgart and became group leader of the Molecular Biotechnology Group in the Institute of Technical Biochemistry (Rolf Schmid group). In 1998, she received a Habilitation Fellowship from the German Science Foundation for “molecular breeding of pathways” and with this project, joined Prof. Arnold’s group at Caltech. In 2000, she joined the faculty at the University of Minnesota.
Current research efforts in her group focus on using synthetic biology approaches for the design of genetically programmable materials for biosynthesis, biocatalysis and other applications, including the fabrication of living materials. Another area of expertise in her group is in the engineering of different microbial chassis organisms to produce valuable chemicals. Dr. Schmidt-Dannert has published numerous manuscripts, patents, and book chapters; serves as Editor and board member of several journals and received several awards such as a David and Lucile Packard Fellowship and McKnight Fellow- and Professorships.
View the complete 2023-24 LLE schedule
Questions? Please contact Michael Martino, External Relations Liaison (michael.martino@utoronto.ca)
David Sinton
Professor, Canada Research Chair
Department of Mechanical & Industrial Engineering | University of Toronto
Abstract
The capture and conversion of CO2 – when powered by renewable electricity – presents an opportunity to reduce emissions and de-carbonize the production of fuels and chemicals. These processes will require electrocatalytic systems that provide reactants, electrons, and products at high rate and efficiency, and that are compatible with established upstream and downstream processes. In this talk I will outline our progress on electrochemical systems to meet this challenge. To enable renewably-powered CO2 capture, we have developed an electrochemical capture fluid regeneration strategy that circumvents the thermal process, and associated emissions, of the incumbent system. To convert the captured CO2 we develop a cascade approach, with CO2-to-CO followed by CO-to-products. I’ll close with a discussion on the challenges ahead for the field to achieve commercial viability, stability and scale.
Speaker Bio
David Sinton is a Professor and Canada Research Chair in the Department of Mechanical & Industrial Engineering at the University of Toronto. He is the Academic Director of the Climate Positive Energy Initiative. Prior to joining the University of Toronto, Dr. Sinton was an Associate Professor and Canada Research Chair at the University of Victoria, and a Visiting Associate Professor at Cornell University. He received a BASc from the University of Toronto, MEng from McGill University and his PhD from the University of Toronto. The Sinton group develops fluid systems for applications in energy. The group is application-driven and is currently developing fluid systems for CO2 capture and conversion and to develop energy efficient industrial working fluids.
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