Katie Galloway, Massachusetts Institute of Technology
Host: Prof. Nicole Weckman
Integrating synthetic circuitry into larger transcriptional networks to mediate predictable cellular behaviors remains a challenge within synthetic biology. In particular, the stochastic nature of transcription makes coordinating expression across multiple genetic elements difficult. Further, delivery of large genetic cargoes limits the efficiency of cellular engineering. Thus, our work is focused on the design of highly-compact genetic tools with a minimal genomic footprint. Co-localization of multiple transcriptional units provides a simple method of compact design. However, co-localization introduces the potential for physical coupling between transcriptional units. To address this challenge, we recently developed a theoretical framework for exploring how DNA supercoils—dynamic structures induced during transcription—influence transcription and gene expression in synthetic and native gene systems. Using this model, we find that DNA supercoiling strongly influences the profile of gene expression and that influence is defined by syntax—the relative orientation and position of genetic elements—and the enclosing boundary conditions. In exploring both synthetic and native gene regulatory networks, we find that supercoiling-mediated feedback changes the behaviors accessible to control and supports (or inhibits) the function of transcriptional networks. Importantly, we have recently confirmed several predictions from this model experimentally and used this model to design circuits with massively improved performance in primary cells. Our results suggest that supercoiling couples behavior between neighboring genes, representing a novel regulatory mechanism. Additionally, our predictions suggest why some circuit designs fail and provide a path to improving transgenic designs. Harnessing the insights from our model will enable enhanced transcriptional control, providing a robust method to tune expression levels, dynamics, and noise needed for the construction of transgenic systems for diverse cell engineering applications including cellular reprogramming.
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Katie Galloway is the W. M. Keck Career Development Professor in Biomedical Engineering and Chemical Engineering at Massachusetts Institute of Technology (MIT). Her research focuses on elucidating the fundamental principles of integrating synthetic circuitry to drive cellular behaviors. Her lab focuses on developing integrated gene circuits and elucidating the systems level principles that govern complex cellular behaviors. Her team lever ages synthetic biology to transform how we understand cellular transitions and engineer cellular therapies. Galloway earned a PhD and an MS in Chemical Engineering from the California Institute of Technology (Caltech), and a BS in Chemical Engineering from University of California at Berkeley. She completed her postdoctoral work at the University of Southern California. Her research has been featured in Science, Cell Stem Cell, Cell Systems, and Development. She has won multiple fellowships and awards including the Cellular and Molecular Bioengineering Rising Star, Princeton’s CBE Saville Lecture Award, NIH Maximizing Investigators’ Research Award, the NIH F32, and Caltech’s Everhart Award.
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Questions? Please contact Michael Martino, External Relations Liaison (michael.martino@utoronto.ca)
George Shimizu, University of Calgary
Host: Prof. Mohamad Moosavi
Metal-organic frameworks (MOFs) are transcending from fundamental to applied research, but their use in a large-scale process has not yet been realized. For many industrial uses, MOFs face a challenge of economical performance in a durable, scalable material implementable in an appropriate engineered form. This presentation will deal with three short stories spanning our efforts to design new porous solids while keeping an eye on real-world applications.
The first story concerns the use of MOFs as proton conductors. MOFs offer tunable structures capable of being loaded with protic carrier molecules. Key challenges were initially to enhance stability and levels of proton conduction. Numerous promising examples exist now and a higher technology challenge is the formation of high-performing membranes. Some of our recent work on making high-loaded MOF membranes based on cellulosic composites will be presented.
The second part will deal with a new approach to make MOFs. MOFs typically rely on a reticular (net-based) approach where metal and organic linkers define a topology and pore sizes. We have developed a new route to MOFs where the guest molecules can play a much greater role in structure determination – rather than simply filling the void, determining its structure. This approach relies on robust H-bonded intermediates. Results on the use of this approach for xylene isomer separation will be presented.
Finally, MOFs can be used like a sponge to trap selected gases and release them under some external stimulus (e.g., pressure drop, temperature increase). Such an approach has been challenging for post-combustion carbon capture owing to the presence of water and acid gases in the stream. CO2. We have developed a solid that has moved up the technology ladder, with different academic and industrial partners, to actually be capturing CO2 industrially at 25 tonnes per day scale. This talk will discuss some of the basic science and also the hurdles to translate from milligrams to industrial demonstration including the key aspect of being able to physisorb CO2 in the presence of water.
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George Shimizu completed a Ph.D. (Inorganic Chemistry) at the University of Windsor with Steve Loeb. This was followed by an NSERC postdoctoral position with Fraser Stoddart (Supramolecular Chemistry) at the University of Birmingham and an NSERC Visiting Fellow/Associate Research Officer position with John Ripmeester and Dan Wayner (Functional Materials) at the National Research Council. In 1998, Shimizu moved to the Department of Chemistry at the University of Calgary. Currently, he is a Full Professor and his research concerns novel inorganic-organic materials, mainly metal-organic frameworks.
All group research begins at a very fundamental level, but it is application-directed, and we strive to translate basic science to demonstration. Most work falls in the fields of gas separation with solid sorbents and proton conductors. Three startup companies have emerged from the group’s MOF research. George has received the Strem (2008) and Rio Tinto (2019) Awards for Inorganic Chemistry from the Chemical Institute of Canada and the Alberta Science and Technology Leadership Foundation Award for Energy and Environment Innovation (2021).
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Christine Allen, University of Toronto
Host: Prof. Milica Radisic
The formulation of therapeutic agents in advanced drug delivery systems such as nanoparticles and microparticles can significantly improve their safety and efficacy. However, the design and development of advanced formulations remains expensive, labour-intensive and time consuming with a heavy reliance on the expertise of the formulation development team and composition of formulations that have been approved to date. In the design of these systems, there are a plethora of parameters that must be considered in relation to the drug, material(s) or excipient(s) as well as processing variables. Experimental evaluation of every combination is intractable and at this time it is not possible to predict the performance of specific formulations a priori. As a result, it is likely that some of the formulation candidates that have moved forward to clinical development are not optimal but rather the best that could be achieved with the time and resources available.
Machine learning (ML) has led to significant advances in various fields, such as drug discovery and materials science. In recent years, we have explored integration of ML to discern the relationships between composition, property and performance with a goal towards fast-tracking innovative drug formulation development. In this work, we have identified a lack of robust datasets in the published literature to apply data-driven methods. This has led us to consider strategies such as experimental automation, and more recently to the concept of a materials acceleration platform (MAP), or self-driving laboratory (SDL), that combines automated experimentation with ML-guided experiment planning for the design of advanced drug delivery systems. The integration of such technological advancements in the pharmaceutical sciences has the potential to fast-track preclinical research, improve efficiency in drug development pipelines and thus improve patient access to effective medicines.
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Dr. Christine Allen is a full Professor at the University of Toronto and internationally recognized leader in drug formulation and development with more than 160 publications. She has received numerous career awards and is a fellow of the American Institute for Medical and Biological Engineering, Canadian Academy of Health Sciences, Controlled Release Society (CRS), and the Canadian Society for Pharmaceutical Sciences (CSPS). She has held senior leadership roles including President of CRS (2022 – 2023), President of CSPS (2020 – 2022), Vice-President Ecosystem Development at adMare Bioinnovations (2022 – 2023), Associate Vice-President and Vice Provost Strategic Initiatives at UofT (2019 – 2022) and Interim Dean, Leslie Dan Faculty of Pharmacy (2018 – 2019). She is the co-founder and CEO of a start-up that is transforming pharmaceutical drug development through integration of AI, automation and advanced computing. She is committed to promoting and actioning equity, diversity, inclusion and accessibility in research and innovation.
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Questions? Please contact Michael Martino, External Relations Liaison (michael.martino@utoronto.ca)
Peter Ostafichuk, University of British Columbia
Host: Prof. Jennifer Farmer
Assessment is widely viewed as an integral part of teaching and learning. More than a means to benchmark student performance, effective assessment is a powerful learning activity. In addition, well-constructed assessments allow students to monitor their learning progress and adapt; provide instructors with insights on student development and teaching effectiveness; and help units to evaluate program outcomes as part of continual improvement or accreditation. At the same time, trying to deliver effective assessments in large (and growing) classes with fixed (and often diminishing) resources can be challenging. This talk will explore assessment approaches that address the multiple aforementioned goals while reducing time and resources requirements and allowing scalability to classes of almost any size. Grounded in fundamental principles of effective assessment, multiple evidence-based examples will be featured, including collaborative in-class testing techniques; comparative evaluation and multi-stage peer assessment; and meaningful auto-graded questions suitable for exams and online homework.
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Dr. Peter Ostafichuk is a Professor of Teaching and the Chair of First Year Engineering at the University of British Columbia. He is the Past President of the Canadian Engineering Education Association (CEEA-ACÉG) and leads the national Institute for Engineering Teaching. With over twenty years of experience, Dr. Ostafichuk has delivered courses from first year to graduate level, across multiple subject areas, and in class sizes ranging from 10 to 1000 students. He has authored multiple books related to education and engineering, and he is a recipient of the 3M National Teaching Fellowship, the Engineers Canada Medal of Distinction, the Wighton Fellowship, and many other accolades.
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Ayse Asatekin, Tufts University
Host: Prof. Jay Werber
Membranes offer a highly energy-efficient, simple to operate, scalable and portable separation method for many applications, from water treatment to oil and gas processing to pharmaceutical manufacturing. Yet, their broader use is often limited by insufficient selectivity and/or fouling with complex feeds. There are no commercial membranes that can separate small molecules of similar size in the liquid phase based on their chemical properties. We aim to develop new synthetic polymer membranes that accomplish this by self-assemble and create structures that mimic key features of biological pores like ion channels and porins: Constricted pores <5 nm in diameter that confine permeation, lined with functional groups that interact with the target during passage. Our first approach utilized the self-assembly of zwitterionic amphiphilic copolymers (ZACs), synthesized from a hydrophobic and a zwitterionic monomer. When ZACs are coated onto a support to form a thin film composite (TFC) membrane, self-assembled zwitterionic domains act as a network of nanochannels for water permeation. Our first ZAC-based thin film composite (TFC) membranes were size-selective with an effective pore size of ~1.3-1.5 nm. These membranes are exceptionally fouling resistant. We then developed cross-linkable ZACs (X-ZACs), which enabled us to access smaller effective pore sizes, down to ~0.9 nm, where ion separations are possible. Our membranes with the smallest pore sizes exhibited unprecedented selectivity between equally charged anions, including the highest Cl–/F– selectivity in the literature. This selectivity arises from zwitterion-ion interactions, which affect both ion partitioning and ion diffusivity, further emphasized through nanoconfinement. This opens the door to novel membranes with novel selectivity between molecules and ions of similar size and charge, mediated through channel-solute interactions. More recently, we have been exploring new avenues to prepare membranes the self-assembled nanopores and fouling resistance of ZAC-based membranes, but expand the range of separations accessible. We have developed amphiphilic polyampholytes (APAs), where hydrophobic, anionic, and cationic monomers form a random/statistical terpolymer that is insoluble in water. This approach allows access to a very broad array of functional groups lining the effective nanopores of these membranes, opening the door for complex separations. Alternatively, we have formed amphiphilic polyelectrolyte complex (APEC) membranes by coating consecutive layers of two amphiphilic polyelectrolytes (i.e. water-insoluble copolymers combining a hydrophobic monomer with either an anionic or a cationic monomer). Interestingly, these bilayer membranes exhibit very small effective pore sizes as well as higher permeances, implying selectivity arises from the formation of polyelectrolyte complexes at a thin interface between these layers. These approaches demonstrate a versatile and highly customizable approach for developing novel high-performance membranes.
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Ayse Asatekin is an associate professor in the Chemical and Biological Engineering Department at Tufts University, and Steve and Kristen Remondi Faculty Fellow. She received bachelor’s degrees in chemical engineering and chemistry from the Middle East Technical University (METU) in Ankara, Turkey. She went on to receive her Ph.D. in chemical engineering through the Program in Polymer Science and Technology (PPST) at MIT. She pursued her post-doctoral work with Prof. Karen K. Gleason, also at MIT. She co-founded Clean Membranes, Inc., a start-up company that commercialized a membrane technology that she began developing during her doctoral research, and worked as its Principal Scientist before joining the Tufts faculty in 2012. Novel membrane technologies developed in her lab are currently being commercialized by ZwitterCo, Inc., where she serves as the Senior Scientific Advisor. She is a Senior Member of the National Academy of Inventors, and the recipient of the NSF CAREER Award, Massachusetts Clean Energy Council’s Catalyst Award, and the Turkish American Scientists and Scholars Young Scholar Award. Her research interests are in developing novel membranes for clean water and energy-efficient separations through polymer self-assembly. She is also interested in multi-functional membranes, controlling surface chemistry for biomedical applications, polymer science, and energy storage.
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Join author Jeff Karp to celebrate the launch of his much-anticipated new book, LIT: Life Ignition Tools. The event will feature a conversation between Jeff Karp and University of Toronto Professor Dr. Milicia Radisic, followed by a reading, Q&A, and signing.
About the Speakers
Jeff Karp, PhD, is an acclaimed mentor and biomedical engineering professor at Harvard Medical School and MIT, a Distinguished Chair at Brigham and Women’s Hospital, and a fellow of the National Academy of Inventors. He has dedicated his research to bioinspired medical problem-solving, and his lab’s technologies have led to the formation of twelve companies. The technologies they have developed include a tissue glue that can seal holes inside a beating heart; targeted therapy for osteoarthritis, Crohn’s disease, and brain disorders; “smart needles” that automatically stop when they reach their target; a nasal spray that neutralizes pathogens; and immunotherapy approaches to annihilate cancer. Dr. Karp is also head of innovation at Geoversity, Nature’s University, a rainforest conservancy located in one of the top biodiversity hotspots in the world. He was selected as the Outstanding Faculty Undergraduate Mentor among all faculty at MIT and the top graduate student mentor of Harvard-MIT students. Dr. Karp lives in Brookline, Massachusetts, with his wife, children, and two Cavalier King Charles spaniels.
Dr. Milica Radisic is a Professor at the University of Toronto, Tier 1 Canada Research Chair in Organ-on-a-Chip Engineering and a Senior Scientist at the Toronto General Research Institute. She is also Director of the NSERC CREATE Training Program in Organ-on-a-Chip Engineering & Entrepreneurship and a co-lead for the Center for Research and Applications in Fluidic Technologies. She is a Fellow of the Royal Society of Canada-Academy of Science, Canadian Academy of Engineering, the American Institute for Medical & Biological Engineering, Tissue Engineering & Regenerative Medicine Society as well as Biomedical Engineering Society. Her impressive accolades include being recognized in the MIT Technology Review Top 35 Under 35, as well as receiving the Queen Elizabeth II Diamond Jubilee Medal, NSERC E.W.R Steacie Fellowship, YWCA Woman of Distinction Award, Killam Fellowship, Acta Biomaterialia Silver Medal, and Humboldt Research Award to name a few. Her research focuses on organ-on-a-chip engineering and development of new biomaterials that promote healing and attenuate scarring.
About LIT: Life Ignition Tools
In the age of convenience, information overload, and endless exposure to stimuli, it’s easy to trudge through the motions of life, pressured, distracted, and seeking instant gratification. When this way of living becomes the norm, it can immobilize us, making it feel impossible to reclaim control of our lives with intention and enthusiasm.
In LIT (William Morrow; April 9, 2024), Harvard Medical School professor, Mass General Brigham and MIT researcher, and renowned bioinspirationalist Jeff Karp, PhD, teaches us to harness the vital wisdom and power of nature to place us into a lit state. Lit is a life magnifier, a heightened state of awareness that drives curiosity, connection, and energy. In short: being lit takes us off autopilot and helps us stay alert, present, and fully engaged.
Diagnosed with learning differences and ADHD at a young age, Karp persisted through nearly insurmountable struggles. After discovering that he could think about thinking at age seven, he became his own science experiment, tapping into the lit state through trial and error to achieve hyper-awareness and explore his curiosity, creativity, and connection to nature. Decades later, as a biotech innovator, husband, and father, lit continues to encourage opportunities for innovation in his professional and personal lives.
He has honed those methods into a diverse toolkit that he calls Life Ignition Tools (LIT), which help us:
- Break out of habitual thinking to discover our own imaginative power.
- Stimulate creativity and excitement at work.
- Integrate our spiritual and personal lives to repair and deepen our relationships.
- Navigate multiple streams of sensory input and manage information overload.
Lit has inspired Dr. Karp’s innovative medical discoveries such as surgical glue inspired by slugs, a diagnostic for cancer based on the tentacles of jellyfish, and surgical staples based on the quills of a porcupine – but you don’t have to be a scientist to live lit. Anyone can use these principles to redirect their lives with energy, focus, creativity, and motivation to create the lives they truly want to lead.
Abstract
Sustainability has many facets and, in this presentation, I will share my recent research endeavors aimed at advancing sustainability in the realms of energy, water, and medicine. The first part of my talk delves into electrochemical transport phenomena in energy storage systems, with a focus on Li plating and dendritic growth on graphite/Li-metal anode, which are the leading causes of degradation and catastrophic failure for batteries under fast charging conditions. Deep understanding of these phenomena would facilitate the design of strategies to reduce, or completely suppress, the onset of lithium plating on the graphite anode, and the instabilities characterizing electrodeposition on the lithium metal anode.
In the second part of my talk, I will present my recent work on the efficient estimation of evapotranspiration for smart agriculture. This includes advancements that accelerate computational time by two orders of magnitude compared to the current standard approach. Finally, I will discuss two biomedical applications: blood transfusion and hypertonic treatment of acute respiratory distress syndrome (ARDS). These efforts contribute to sustainable energy conversion and storage, sustainable agricultural practices, and sustainable blood management, steering us towards a more sustainable future.
Biography
Weiyu Li is a postdoctoral scholar in the Departments of Physics and Materials Science and Engineering at Stanford University. Her research focuses on modeling and simulation of electrochemical transport in energy storage systems. She received her PhD in Energy Science and Engineering from Stanford University. Her other research interests include data assimilation and biomedical modeling. Prior to her doctoral studies, Weiyu obtained her M.Sc. degree in Mechanical and Aerospace Engineering from Princeton University. Weiyu is the sole recipient of the Siebel Scholars Award in Energy Science, class of 2023. She has also received Henry J. Ramey Fellowship Award at Stanford University, and the Princeton University Fellowship in Natural Sciences and Engineering.
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Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder for which there are two FDA-approved anti-fibrotic drugs, nintedanib, and pirfenidone. While these drugs slow the rate of decline in lung function, responses are variable and side effects are common. Using an in-silico data-driven approach, we identified a strong inverse connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications. Accordingly, we investigated the anti-fibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: (i) in vitro in normal human lung fibroblasts (NHLFs); (ii) in vivo in bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-β) murine models of pulmonary fibrosis; and (iii) ex vivo in mice and human precision cut lung slices from these two murine models as well as from patients with IPF and healthy donors. In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone. Transcriptomic analyses of TGF-β-stimulated NHLFs identified specific gene sets associated with fibrosis including epithelial mesenchymal transition (EMT), TGF-β, and WNT signaling that was uniquely altered by saracatinib. Transcriptomic analysis of whole lung extracts from the two animal models of pulmonary fibrosis revealed that saracatinib reverted many fibrogenic pathways including EMT, immune responses, and extracellular matrix organization. Amelioration of fibrosis and inflammatory cascades in human precision cut lung slices confirmed the potential therapeutic efficacy of saracatinib in human lung fibrosis. These studies identify novel Src-dependent fibrogenic pathways and support the study of the therapeutic effectiveness of saracatinib in IPF treatment.
Biography
Dr. Downey received his MD from the University of Manitoba and completed Internship and Residency in Internal Medicine at Harvard Medical School, Beth Israel and Brigham and Women’s Hospital, Boston. He then completed clinical training in Pulmonary and Critical Care Medicine at the University of Colorado, Denver. He undertook post-doctoral research training in Immunology in the laboratory of Dr. Peter Henson at National Jewish Health. He was appointed Assistant Professor at the University of Toronto rising through the ranks to become the Director of the Division of Respirology, Professor and Vice-Chair, Department of Medicine, and the recipient of a Tier 1 Canada Research Chair in Respiration Sciences. Dr. Downey returned to Colorado as Executive Vice President of Academic Affairs and Provost and Professor of Medicine, Pediatrics, and Immunology and Genomic Medicine at National Jewish Health, and Professor of Medicine and Immunology and Microbiology and Associate Dean of the School of Medicine, University of Colorado. His current research interests include innate immunity, signaling mechanisms involved in acute lung injury/ARDS, the effects of particulate matter exposure on lung health, and mechanisms and treatment of pulmonary fibrosis. His research has been funded by the National Institutes of Health, the Canadian Institutes of Health Research, and the US Department of Defense for over 30 years. Dr. Downey has >250 publications in top ranked journals including the New England Journal of Medicine, Science, Science Translational Medicine, Nature Cell Biology, the Journal of Cell Biology, the American Journal of Respiratory and Critical Care Medicine, the Journal of Experimental Medicine, Blood, PNAS, the American Journal of Respiratory Cell and Molecular Biology, and the Journal of Immunology and his work has been cited over 23,000 times by other authors (h-index 83). Dr. Downey is a member of the American Society for Clinical Investigation, the Association of American Physicians, the American Thoracic Society, the American College of Chest Physicians, the Royal College of Physicians and Surgeons of Canada. He currently serves as the Immediate Past President of the American Thoracic Society.
This talk presents some preliminary findings from an in-process study of hydrocarbon-eating microbes and the humans who have discovered, researched, cared for, grown, killed, sold, and otherwise interacted with them. Following some discussion of why this topic seems of interest in and beyond anthropology and science/technology studies, I focus on some historical examples that range from the early years of petroleum microbiology in Russia through the Cold War-era race to develop “petroprotein.” I conclude with some questions prompted by contemporary research in this field, including but not limited to bioremediation.
Douglas Rogers
is Professor of Anthropology at Yale University and author of two award-winning books about Russia. For the past few years, he has been collecting materials for a new research project about the history and contemporary practice of petroleum microbiology and biotechnology. He was recently named a 2024 Fellow of the John Simon Guggenheim Memorial Foundation.
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Academic libraries are facing a myriad number of challenges and opportunities ahead. AI is just one example. Paint a picture of the science library of the future – what will it offer to remain core to teaching, learning, research and the overall student experience? How will you, as a leader, prepare the health science and science libraries for that future?
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