Cell and Systems Biology

Institute of Biomedical Engineering

Leah Cowen

Sinai Health

Sunnybrook Health Sciences Centre

Unity Health

Centre for Addiction and Mental Health

Anthropology

Astronomy & Astrophysics

Biochemistry

Chemistry

Computer Science

Dalla Lana School of Public Health

Ecology and Evolutionary Biology

Hospital for Sick Children

Laboratory Medicine and Pathobiology

Leslie Dan Faculty of Pharmacy

Mathematics

Physics

Psychology

University Health Network

UTIAS

Subheadline

From better batteries to preventing memory loss, nearly four dozen projects at U of T and its partner hospitals are being supported by the Ontario Research Fund

Researchers in the ��Ƶ’s Thermal Management Systems (TMS) Laboratory are working to improve the way battery systems handle heat and develop structural battery pack components. 

“Whether they are being used for electric vehicles or for stationary energy storage systems that reduce strain on the grid, lithium-ion batteries are transforming the way we use electricity,” said Carlos Da Silva, senior research associate at the TMS Lab in the Faculty of Applied Science & Engineering and executive director of U of T’s Electrification Hub.

“Unfortunately, today’s batteries are still sensitive to temperature: if they get too cold or too hot, it can degrade their performance and even present safety risks. We are working on new technologies that make batteries more resilient to thermal fluctuations.”

The battery-related research is among nearly four dozen projects at U of T and its partner hospitals that are receiving almost $35 million in support through the Ontario Research Fund – Research Excellence (ORF-RE) and the Ontario Research Fund – Small Infrastructure (ORF-SIF). (See the full list of projects and their principal researchers below).

"Research at the ��Ƶ and at all universities and colleges across Ontario is the foundation of the province’s competitiveness now and in the future,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives.

“This investment protects and advances cutting-edge, made-in-Ontario research in important economic sectors and helps ensure universities can continue to train, attract and retain the world’s top talent."

At U of T Engineering’s TMS Lab, researchers led by Cristina Amon, a University Professor in the department of mechanical and industrial engineering, are working on two funded projects. They are developing advanced computational modelling and digital twin methodologies that predict and optimize how heat flows through battery packs. The methodologies are carefully calibrated and validated through industry-relevant experiments in the lab.

Senior Research Associate Carlos Da Silva, left, and University Professor Cristina Amon, right, chat in the Faculty of Applied Science & Engineering's Thermal Management Systems Laboratory (photo by Aaron Demeter)

These methodologies will help battery designers anticipate and prevent thermal management challenges before they arise. It can also enable them to optimize the design and deployment of fire mitigation measures, such as ultra-thin heat barriers, within their battery systems.

The team is also collaborating with Ford Canada and several other companies in the energy storage space. For example, they have worked with Jule (powered by eCAMION) on the development of direct current electric vehicle fast chargers with integrated battery energy storage systems, one of which was recently unveiled on the U of T campus.

“We are grateful for this ORF-RE funding, which will accelerate our research and help us further expand our partnerships, ensuring that battery thermal innovations have a seamless transition from the lab to the marketplace,” Amon said.

“As a result of this work, the next generation of batteries will be safer and more resilient than ever before, which is especially important in colder climates like ours here in Ontario.” 

Ontario Research Fund – Research Excellence:

Cristina Amon in the department of mechanical & industrial engineering in the Faculty of Applied Science & Engineering – Powering Ontario’s grid transformation and electric vehicle fast charging with thermally resilient battery energy storage & Next-gen electric vehicle battery systems: Lightweight, thermally performant and fire safe for all climates
Morgan Barense in the department of psychology in the Faculty of Arts & Science – HippoCamera: Digital memory rehabilitation to combat memory loss
Aimy Bazylak in the department of mechanical & industrial engineering in the Faculty of Applied Science and Engineering – RECYCLEAN: Critical minerals recycling & re-manufacturing for the energy transition
Ian Connell at University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine – MRI-compatible innovations for neuromodulation
Simon Graham at Sunnybrook Health Sciences Centre and the department of medical biophysics in the Temerty Faculty of Medicine – Technological innovations for clinical MRI of the brain at 7 tesla
Clinton Groth in the Institute for Aerospace Studies in the Faculty of Applied Science & Engineering – Hydrogen as a sustainable aviation fuel – combustion research to remove impediments to adoption in gas turbine engines
James Kennedy at Centre for Addiction and Mental Health and the department of psychiatry in the Temerty Faculty of Medicine – Clinical utility and enhancements of a pharmacogenomic decision support tool for mental health patients
Shaf Keshavjee at University Health Network and the department of surgery in the Temerty Faculty of Medicine – Advanced solutions to human lung preservation and assessment using artificial intelligence
Aviad Levis in the department of computer science in the Faculty of Arts & Science – AI and quantum enhanced astronomy
JoAnne McLaurin at Sunnybrook Health Sciences Centre and the department of laboratory medicine & pathobiology in the Temerty Faculty of Medicine – Conversion of astrocytes to neurons to treat neurodegenerative diseases of the brain and the eye
R. J. Dwayne Miller in the department of chemistry in the Faculty of Arts & Science – PicoSecond InfraRed Laser (PIRL) “cancer knife” with complete biodiagnostics via spatial imaging mass spectrometry
Javad Mostaghimi in the department of mechanical & industrial engineering in the Faculty of Applied Science & Engineering – A new generation of compact, transportable mass spectrometers for rapid, in-field sample analysi
Xiao Yu (Shirley) Wu in the Leslie Dan Faculty of Pharmacy – Molecular dynamics modeling and screening of excipients for designing amorphous solid dispersion formulations of poorly–soluble drugs

Ontario Research Fund – Small Infrastructure Fund:

Celina Baines in the department of ecology & evolutionary biology in the Faculty of Arts & Science – Impacts of environmental change on organismal movement
Sergio de la Barrera in the department of physics in the Faculty of Arts & Science – Facility for quantum materials and device assembly from atomically thin van der Waals layers
Michelle Bendeck in the department of laboratory medicine & pathobiology in the Temerty Faculty of Medicine – 4D quantitative cardiovascular physiology centre
Laurent Bozec in the department of laboratory medicine & pathobiology in the Temerty Faculty of Medicine – 21st Century challenge for Dentistry: Breaking the cycle of irreversible dental tissue loss
Mark Chiew at Sunnybrook Health Sciences Centre and the department of medical biophysics in the Temerty Faculty of Medicine – Next generation computational MRI for rapid neuroimaging and image-guided therapy
Haissi Cui in the department of chemistry in the Faculty of Arts & Science – A molecule to mouse approach to study the intracellular localization of genetic code interpretation in mammalian cells
Andy Kin On DeVeale at the University Health Network and the Dalla Lana School of Public Health – Sarcopenia and musculoskeletal interactions (sami) collaborative hub
Ali Dolatabadi in the department of mechanical & industrial engineering in the Faculty of Applied Science & Engineering – Advanced cold spray facility
Spencer Freeman at the Hospital for Sick Children and the department of biochemistry in the Temerty Faculty of Medicine – Imaging biophysical determinants of the innate immune response
Liisa Galea at the Centre for Addiction and Mental Health and the Institute of Medical Science in the Temerty Faculty of Medicine – Sex and sex-specific factors influencing brain health across the lifespan
Maged Goubran at Sunnybrook Health Sciences Centre and the department of medical biophysics in the Temerty Faculty of Medicine – AI platform for mapping, tracking and predicting circuit alterations in Alzheimer’s disease
Eitan Grinspun in the departments of computer science and department of mathematics in the Faculty of Arts & Science – A computer graphics perspective on entanglement of slender structures
Levon Halabelian in the Department of Pharmacology and Toxicology in the Temerty Faculty of Medicine – Enabling a high-throughput drug discovery pipeline for targeting disease-related human proteins
Ziqing Hong in the department of physics in the Faculty of Arts & Science – Ultra-sensitive cryogenic detector development for dark matter and neutrino experiments
Eno Hysi at the Unity Health Toronto and the department of medical biophysics in the Temerty Faculty of Medicine – Structural and functional assessments of diabetic skin microvasculature using photoacoustic imaging
Lewis Kay in the department of biochemistry in the Temerty Faculty of Medicine – Helium recovery system for the biomolecular NMR facility
Xiang Li in the department of chemistry and the department of physic in the Faculty of Arts & Science – Real-time multi-faceted probes of quantum materials
Qian Lin in the department of cell & systems biology in the Faculty of Arts & Science – 2p-RAM for whole-brain single-neuron imaging of behaving zebrafish to study neural mechanisms of cognitive behaviours
Xilin Liu in the Edward S. Rogers Sr. department of electrical and computer engineering in the Faculty of Applied Science & Engineering – Integrated circuits for wireless brain implants with multi-modal neural interfaces
Stephen Lye at the Sinai Health System and the department of physiology in the Temerty Faculty of Medicine – Healthy Life Trajectories Initiative (HeLTI) analytics platform
Caitlin Maikawa in the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering – Biointerfacing materials for drug delivery lab
Emma Master in the department of chemical engineering & applied chemistry in the Faculty of Applied Science & Engineering – Accelerating biomanufacturing innovation through enhanced capacity for scale-up and downstream bioprocess engineering
Roman Melnyk at the Hospital for Sick Children and the department of biochemistry in the Temerty Faculty of Medicine – The H-SCREEN: A platform for high throughput and high content imaging-based small molecule screens for disease modulation
Juan Mena-Parra in the department of astronomy & astrophysics in the Faculty of Arts & Science – An advanced laboratory to enable novel radio telescopes for cosmology and time-domain astrophysics
Seyed Mohamad Moosavi in the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering – Machine learning for nanoporous materials design
Enid Montague in the department of mechanical & industrial engineering in the Faculty of Applied Science & Engineering – Automation and equity in healthcare laboratory
Michael Norris in the department of biochemistry in the Temerty Faculty of Medicine – Infrastructure for structural and functional virology research hub
Amaya Perez-Brumer in the Dalla Lana School of Public Health – 3P lab: Centering power, privilege and positionality for health equity research
Monica Ramsey in the department of anthropology at the ��Ƶ Mississauga – Ramsey Laboratory for Environmental Archaeology (RLEA): How human-environment interactions shaped plant-food
Arneet Saltzman in the department of cell & systems biology in the in the Faculty of Arts & Science – Heterochromatin regulation in development and inheritance
Mina Tadrous in the Leslie Dan Faculty of Pharmacy – Developing a centre for real-world evidence to improve the use of medications for Canadians
Shurui Zhou in the department of electrical & computer engineering in the Faculty of Applied Science & Engineering – Improving collaboration efficiency for fork-based software development
Olena Zhulyn at the Hospital for Sick Children and the department of molecular genetics in the Temerty Faculty of Medicine – Targeting translation for tissue regeneration and repair
Christoph Zrenner at the Centre for Addiction and Mental Health and the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering – Next-generation real-time closed-loop personalized neurostimulation

Soil’s secret language: U of T researchers decode plant-to-fungi communication

Christopher.Sorensen — Wed, 13 Nov 2024 21:07:22 +0000

Soil’s secret language: U of T researchers decode plant-to-fungi communication

Christopher.Sorensen Wed, 11/13/2024 - 16:07

Cutline

The interaction between fungi and plant hormones could be harnessed to yield hardier crops, reduce fertilizer use and minimize phosphate run-off into waterways, according to a new study by U of T researchers (photo by iStock|amenic181)

Neil Macpherson

Topic

Subheadline

The discovery could lead to new strategies for cultivating hardier crops and combatting disease-causing fungi

Researchers at the ��Ƶ have cracked the code of plant-to-fungi communication.

Using baker’s yeast, the researchers discovered that the plant hormone strigolactone (SL) activates fungal genes and proteins associated with phosphate metabolism, a system that is key to growth.

This insight into how fungi respond to chemical signals at the molecular level – detailed in a new study published in the journal Molecular Cell – could lead to new strategies for cultivating hardier crops and combatting disease-causing fungi.

Shelley Lumba (supplied image)

“As we begin to understand how plants and fungi communicate, we will better understand the complexities of the soil ecosystem, leading to healthier crops and improving our approach to biodiversity,” says Shelley Lumba, lead author and assistant professor in the department of cell and systems biology in U of T’s Faculty of Arts & Science.

In the soil, plant roots engage with fungi in a silent molecular “language” to direct their structure. When plants release SLs, they signal fungi to attach to their roots, providing phosphates – the fuel plants need to grow, and a major component of most fertilizers – in exchange for carbon.

For the study, Lumba and her fellow researchers investigated why and how fungi respond to SLs. Eighty per cent of plants rely on this symbiotic relationship, and enhancing this interaction with beneficial fungi could yield hardier crops, reduce fertilizer use and minimize phosphate runoff into waterways.

For the study, Lumba and her fellow researchers investigated why and how fungi respond to the plant hormone strigolactone. Illustration: Bradley et al., 2024, Molecular Cell 84, 1–17.

In other cases, disease-causing fungi can exploit chemical cues to infect crops, sometimes wiping out entire harvests. Understanding this chemical language could also help block such pathogens.

The researchers treated baker’s yeast with SLs and observed which genes were turned off and on in response. They found that this chemical signal increased the expression of genes labelled “PHO” that are related to phosphate metabolism. Further analysis showed that SLs function through Pho84, a protein on the surface of yeast that monitors phosphate levels, activating a cascade of other proteins in the phosphate pathway.

The researchers determined that plants release SLs when starved for phosphate, signalling the yeast to change its phosphate uptake.

They found the phosphate response to the SL signal holds true not only for domesticated fungi such as baker’s yeast but also for wild fungi – specifically the detrimental wheat blight Fusarium graminearum and the beneficial symbiotic fungus Serendipita indica.

“Gene expression as an output from chemical treatment is key to this approach – it identifies the effect of the SL response on fungal growth.” says Lumba.

Scientists can use this straightforward method to systematically identify plant-derived small molecules that communicate with fungi. Enhancing the interaction with beneficial fungi could lead to advances in agriculture and mitigate pollution and food insecurity.

“The potential impact of this research can improve the lives of so many,” says Lumba. “It’s about healthy soil for a healthy planet.”

With files from A&S News

A master neuron controls movement in worms, with implications for human disease: Study

Christopher.Sorensen — Thu, 16 May 2024 15:01:59 +0000

A master neuron controls movement in worms, with implications for human disease: Study

Christopher.Sorensen Thu, 05/16/2024 - 11:01

Cutline

Researchers at the Lunenfeld-Tanenbaum Research Institute have revealed the crucial role of a neuron called AVA in controlling the worm C. elegans’s ability to shift between forward and backward motion ( photo by ZEISS Microscopy from Germany)

Jovana Drinjakovic

Topic

Sinai Health

Molecular Genetics

Subheadline

The discovery offers a major new insight into a neural circuit that scientists have studied since the inception of modern genetics.

Researchers at Sinai Health and the ��Ƶ have uncovered a mechanism in the nervous system of the tiny roundworm C. elegans that could have significant implications for treating human diseases and advancing robotics.

The study, led by Mei Zhen and colleagues at the Lunenfeld-Tanenbaum Research Institute, was published in the journal Science Advances and reveals the crucial role of a specific neuron called AVA in controlling the worm’s ability to shift between forward and backward motion.

Crawling towards food sources and swiftly reversing from danger is a matter of life and death for the worms. This type of behaviour, where two actions are mutually exclusive, is common in many animals including humans – we cannot sit and run at the same time, for example.

Scientists long believed that control of movements in worms was due to straightforward reciprocal actions between two neurons: AVA and AVB. The former was thought to promote backward motion while AVB facilitated forward motion, with each neuron inhibiting the other to control movement direction.

However, the new data from Zhen’s team challenge this notion, uncovering a more complex interaction where the AVA neuron plays a dual role. It not only instantly stops forward motion by inhibiting AVB, but also maintains a longer-term stimulation of AVB to ensure a smooth transition back to forward movement.

The discovery highlights the AVA neuron’s ability to finely control movement through distinct mechanisms, depending on different signals and across different time scales.

“In terms of engineering, this is a very economical design,” said Zhen, who is also a professor of molecular genetics in U of T’s Temerty Faculty of Medicine. “The strong, robust inhibition of the backward circuit allows the animals to respond to bad environments and escape. At the same time, the controller neuron continues to put in constitutive gas into the forward circuit to generate movement towards safer places.”

Jun Meng, a former PhD student in the Zhen lab who led the research, said understanding how animals transition between such opposing motor states is crucial for insights into how animals move as well as neurological disorder research – and that the worms provide a unique window into basic neural wiring that's to their simple, see-through bodies.

The discovery that the AVA neuron plays such a dominant role offers a major new insight into the neural circuit that scientists have studied since the inception of modern genetics over half a century ago. The Zhen lab successfully leveraged cutting-edge technology to precisely modulate the activity of individual neurons and record data from living worms in motion.

Zhen, who is also a professor of cell and systems biology at U of T’s Faculty of Arts & Science, emphasizes the importance of interdisciplinary collaboration in this research. Meng performed key experiments, while neuronal electrical recordings were conducted by Bin Yu, a PhD student in Shangbang Gao’s lab at Huazhong University of Science and Technology in China.

Tosif Ahamed, a former post-doctoral researcher in the Zhen lab and now a Theory Fellow at the HHMI Janelia Research Campus in the United States, led mathematical modelling efforts that were crucial for testing hypotheses and gaining the new insights.

The findings provide a simplified model to study how neurons can manage multiple roles in movement control – a concept that might extend to human neurological conditions.

For example, AVA’s dual role depends on its electric potential, which is regulated by ion channels on its surface. Zhen is already exploring how similar mechanisms could be involved in a rare condition known as CLIFAHDD syndrome, caused by mutations in similar ion channels. Additionally, the new findings could inform the development of more adaptable and efficient robotic systems capable of complex movements.

“From the origin of modern science to the forefront of today’s research, model organisms like C. elegans have been instrumental in peeling back the layers of complexity in our biological systems," said Anne-Claude Gingras, director of the Lunenfeld-Tanenbaum Research Institute, vice-president of research at Sinai Health and a professor of molecular genetics in U of T’s Temerity Faculty of Medicine.

“This research is a great example of how much we can learn from simple animals, to then think about applying this new knowledge to advancing medicine and technology.”

The research was supported by the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council of Canada, the National Natural Science Foundation of China and the European Research Council.

Remembering Yoshio Masui, renowned cell biologist and longtime U of T professor

rahul.kalvapalle — Fri, 26 Apr 2024 18:20:01 +0000

Remembering Yoshio Masui, renowned cell biologist and longtime U of T professor

rahul.kalvapalle Fri, 04/26/2024 - 14:20

Cutline

Professor Emeritus Yoshio Masui is credited with helping make developmental biology an essential discipline (supplied image)

Topic

Subheadline

Professor Emeritus Yoshio Masui's career at U of T spanned more than half a century

The ��Ƶ is mourning the death of Yoshio Masui, a professor emeritus in the departments of zoology (1968 to 2006) and cell and systems biology (2006 to 2024) in the Faculty of Arts & Science and a celebrated cell biologist who spent more than half a century at the university.

Born in Kyoto, Japan in 1931, Masui earned undergraduate, master’s and doctoral degrees in Kyoto University before coming to U of T in 1968, driven by a desire for “freedom for research – neither interference with nor solicitation for choices of research projects”.

Masui made several important discoveries, including revealing details on how eggs mature and uncovering clues as to how cancer can arise from uncontrolled cell growth. He played a key role in making developmental biology an essential discipline, and earned numerous honours including the Order of Canada, Albert Lasker Medical Research Award and Gairdner International Award.

Described as “one of Canada’s finest scientists” by the Order of Canada, Masui was revered by colleagues and students for his wisdom, curiosity and generosity. He died on April 18 at the age of 93.

Read the Faculty of Arts & Science article about Professor Emeritus Yoshio Masui

Researchers use powerful AI tool to gain new insights into protein structures

Christopher.Sorensen — Fri, 03 Nov 2023 16:35:45 +0000

Researchers use powerful AI tool to gain new insights into protein structures

Christopher.Sorensen Fri, 11/03/2023 - 12:35

Cutline

A protein containing amino acids with fixed spiral and ribbon structures, in blue and light blue, as well as thread-like disordered regions in orange (photo by AlphaFold Protein Structure Database (CC BY 4.0).

Chris Sasaki

Topic

Hospital for Sick Children

Global

Subheadline

The findings could lead to a better understanding of the role played by proteins in disease and the development of new treatments

An international team of researchers has revealed new insights about the three-dimensional structure of certain types of proteins by using the powerful artificial intelligence tool AlphaFold2.

Long molecules comprising strings of amino acids, proteins are folded into three-dimensional structures according to a strict set of rules. The myriad of different structures enable proteins to perform their functions. Within organisms, from bacteria to humans, they transport molecules, act as catalysts for chemical processes, operate as valves and pumps – and much more.

While AlphaFold2 has predicted the three-dimensional structure of some 200 million proteins, it has until now been unable to determine whether sections within certain proteins, known as intrinsically disordered regions (IDRs), have any structure at all – much less predict the shape of that structure.

Alan Moses (supplied image)

“This has been a long-standing debate amongst biochemists and molecular biologists – whether IDRs have fixed structure or whether they’re just ‘floppy’ parts of proteins,” says Alan Moses, a computational biologist and professor in the department of cell and systems biology in the ��Ƶ’s Faculty of Arts & Science.

“We confirmed that, [while] AlphaFold2 still can't predict the structure of IDRs very well ... what it can do is tell us which IDRs are likely to have some structure – something that was previously impossible.”

Moses is a co-author of a new paper, published in the journal Proceedings of the National Academy of Sciences, that details the research team’s findings and could lead to a better understanding of the role played by these proteins in disease and to the development of new drug treatments.

His co-authors include Reid Alderson, a post-doctoral researcher with the Medizinische Universität Graz (MUG) who formerly did post-doctoral work at U of T; Julie Forman-Kay, a senior scientist and program head of molecular medicine at the Hospital for Sick Children and a professor of biochemistry in U of T’s Temerty Faculty of Medicine; Desika Kolaric, a research assistant at MUG; and Iva Pritišanac, an assistant professor at MUG and former post-doctoral researcher in Moses’s lab.

The team’s findings are significant because AlphaFold2 wasn't trained to predict structures in IDRs and IDRs were not included in its training data. “It's like AI being trained to drive a car, and then trying to see if it can also drive a bus,” says Moses. “It can't drive the bus all that well, but it can recognize that someone should be driving.”

The team is also the first to do it systematically for all the proteins in humans and other organisms. “So, for the first time we believe we know how often it is happening,” says Moses. “This is important because biology is full of exceptions. We need to know what’s common and what’s exceptional.”

The development of this powerful and unexpected application of AlphaFold2 demonstrates the power of using AI to solve the protein folding problem and will improve researchers’ understanding of IDRs and their role in disease.

“In the IDRs that AlphaFold2 predicts to have some structure, we’ve shown that mutations are far more likely to cause disease than mutations in other structureless IDRs,” says Moses. “This is an important advance in understanding how mutations in IDRs can cause disease, which is generally not well understood. We now believe that many of the mutations are disrupting the structure somehow.

“What’s more, because AlphaFold2 predictions are already available for all proteins, now we can say for the first time how many IDRs across the tree of life have structure. Our paper shows that bacterial IDRs are much more likely to have structure than human and animal IDRs. As far as we know, this is the first time this has been noticed and it may settle the ongoing debate about whether most IDRs have structures or not.”

Certain cancers can activate 'enhancer' in the genome to drive tumour cell growth: Study

Christopher.Sorensen — Mon, 16 Oct 2023 14:30:36 +0000

Certain cancers can activate 'enhancer' in the genome to drive tumour cell growth: Study

Christopher.Sorensen Mon, 10/16/2023 - 10:30

Cutline

(Photo by Ewa Krawczyk, National Cancer Institute \ Georgetown Lombardi Comprehensive Cancer Center, National Institutes of Health)

Neil Macpherson

Topic

Cancer

Graduate Students

Researchers at the ��Ƶ have found that cancer cells can enhance tumour growth by hijacking enhancer DNA normally used when tissues and organs are formed.

The mechanism, called “enhancer reprogramming,” occurs in bladder, uterine, breast and lung cancer – and could cause these types of tumors to grow faster in patients.

Jennifer Mitchell (supplied image)

The research was conducted in the lab of Jennifer Mitchell, a professor in the department of cell and systems biology in the Faculty of Arts & Science, and published recently in the journal Nucleic Acids Research. It pinpoints the role that specific proteins play in regulating the enhancer region which may lead to improved treatments for these cancer types.

Living cells, even cancer cells, follow instructions in the genome to turn genes on and off in different contexts, says first author Luis Abatti, a PhD candidate in Mitchell’s lab.

“The genome is like a recipe book written in DNA that gives instructions on making all the parts of the body,” Abatti says.

“In each organ, only the recipes relevant to that organ should be followed – whether it’s the instructions for lung, breast or some other tissue. Like flipping pages in a recipe book, the DNA containing the instructions for turning genes on in the lung is open and used in the lung, for example, but closed and ignored in other types of cells.

Luis Abatti (supplied image)

“We know that some cancer cells are opening the wrong pages in the recipe book – ones that contain the SOX2 gene, which can cause tumours to grow uncontrollably. We wanted to find out: How does the gene become expressed in cancer cells?”

The researchers analyzed genome data to look for enhancer DNA that could activate SOX2 in cancer cells. The enhancer they found is open in many different types of patient tumours, meaning this could be a cancer enhancer active in bladder, uterus, breast and lung tumours. Unlike many cancer-causing changes, the enhancer reprogramming mechanism does not arise out of mutation due to DNA damage – it is caused by part of the genome opening when it should be staying closed.

The researchers then determined that the enhancer causes increased cancer cell growth because when they removed the enhancer in lab-grown cells, the cancer cells created fewer new tumour colonies.

To figure out why cells have a DNA region that makes cancer worse, the team examined mice without this DNA region and found they do not form a separate passage for air and food in their throat as they develop. Thus, this potentially dangerous cancer-enhancer region is likely in the human genome to regulate airway formation as the human body forms. However, if a developing cancer cell opens this region, it will form a tumour that grows faster and is more dangerous for the patient.

The researchers unravel the mechanism of how developmentally active enhancers become repurposed in a tumour (image: © Abatti et al, 2023, published by Oxford University Press on behalf of Nucleic Acids Research)

“We also found that two proteins known to have a role in the developing airways – FOXA1 and NFIB – are now regulating SOX2 in breast cancer,” says Mitchell, who is associate chair of research in the department of cell and systems biology and is cross-appointed to the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine.

The enhancer is activated by the FOXA1 protein and suppressed by the NFIB protein. This means that drugs suppressing FOXA1 or activating NFIB may lead to improved treatments for bladder, uterine, breast and lung cancer.

“Now that we know how the SOX2 gene is activated in certain types of cancers, we can look at why this is happening,” Mitchell says.

“Why did the cancer cells end up on the wrong page of the genome recipe book?”

The research received support from the Canadian Institutes of Health Research, the Canada Foundation for Innovation and the Ontario government.

Researchers discover new protein needed for rapid wound repair

siddiq22 — Wed, 07 Jun 2023 20:35:11 +0000

Researchers discover new protein needed for rapid wound repair

siddiq22 Wed, 06/07/2023 - 16:35

Cutline

Katheryn Rothenberg, a postdoctoral researcher in U of T's Quantitative Morphogenesis Lab, was lead author on the new study (photo by Qin Dai)

Qin Dai

Topic

Institute of Biomedical Engineering

Medical Research

Subheadline

A new study by researchers from U of T's Faculty of Applied Science & Engineering examines the mechanisms underlying collective cell migration

Researchers from the ��Ƶ's Faculty of Applied Science & Engineering have made progress in understanding the intricate cellular processes involved in tissue development and repair.

The findings, published in the journal Current Biology, shed light on the mechanisms underlying collective cell migration – a fundamental behaviour that plays a crucial role in both normal embryo development and pathological conditions such as cancer metastasis.

“This study advances our understanding of the molecular signals that coordinate cellular behaviours, in embryonic development and tissue repair, and likely also in tumour invasion,” says Rodrigo Fernandez-Gonzalez, a professor in the department of cell and systems biology and the Institute of Biomaterials and Biomedical Engineering who heads the Quantitative Morphogenesis Laboratory.

Researchers found that Rap1 – a molecular switch that regulates cell adhesion and signalling when turned on – plays a role in the formation and remodelling of adherens junctions (protein complexes that occur at cell–cell junctions and cell–matrix junctions in epithelial and endothelial tissue) and the cytoskeleton during the collective cell movements that drive the rapid, scar-less wound healing response in embryos, making it an attractive therapeutic target in the future.

In embryonic wound healing, the cells around the wound move together to seal the lesion. To that end, cells undergo a series of intricate molecular changes. At the centre of these changes, a unique structure called tricellular junction (TCJ) is formed. The TCJ acts as a hub that hosts a series of proteins that are essential in coordinating cell movements.

When researchers tagged the Rap1 protein with a sensor that could be detected by a microscope, they were able to visualize large concentrations of the protein accumulating around the wound, and specifically at the TCJs.

Upon establishing the localization of Rap1 in the hub of wound repair, the researchers set out to find its role in this complex process. By inactivating or reducing the amount of Rap1 in the embryo, they observed a significant reduction in the wound closure rate compared to normal embryos. Conversely, by activating Rap1, the wound closure rate was dramatically accelerated.

“The fact that collective migration speed can be modulated by Rap1 activity provides a potential pathway for either promoting cell migration – for example, to heal chronic wounds or stopping undesired migration like cancer metastasis,” says Katheryn Rothenberg, a postdoctoral researcher in Fernandez-Gonzalez’s lab who led the study.

Researchers also found that Rap1 plays a crucial role in interacting with cell-cell adhesion proteins necessary to maintain cells together as they move to close the wound, and cytoskeletal proteins that cells use to pull on each other and move collectively. They observed that any disruption to Rap1 can greatly impede the speed at which wounds close.

“By unravelling the intricate molecular mechanisms involved, we have uncovered potential targets for therapeutic interventions in various conditions that rely on collective cell migration,” Fernandez-Gonzalez says.

“We are now keen on understanding the upstream signals that turn Rap1 on during wound healing. This understanding would facilitate the development of tools to activate Rap1 in congenital disorders associated with deficient collective cell behaviour, or to inhibit Rap1 when it contributes to spread disease.”

From Africana development to decarbonization: 34 U of T researchers awarded Canada Research Chairs

Christopher.Sorensen — Wed, 16 Nov 2022 19:01:13 +0000

From Africana development to decarbonization: 34 U of T researchers awarded Canada Research Chairs

Christopher.Sorensen Wed, 11/16/2022 - 14:01

Cutline

Scott Gray-Owen, Caroline Hossein and Marianne Hatzopoulou are three of 34 scholars at U of T who were awarded new or renewed Canada Research Chairs (photos by Nick Iwanyshyn, courtesy of Caroline Hossein, by Johnny Guatto)

Scott Anderson

Topic

Sunnybrook Health Sciences

Leah Cowen

Donnelly Centre for Cellular & Biomolecular Research

Unity Health

Institute of Health Policy Management and Evaluation

Astronomy & Astrophysics

Canada Research Chairs

Centre for Addiction and Mental Health

Computer Science

Dalla Lana School of Public Health

Hospital for Sick Children

History

Ontario Institute for Studies in Education

Rotman School of Management

Sociology

U of T Scarborough

University Health Network

Thirty-four scholars at the ��Ƶ have been awarded new or renewed Canada Research Chairs in fields ranging from artificial intelligence to health and history.

Many of the Canada Research Chairs are working on topics related to complex global challenges – advancing knowledge that will help accelerate the transition to clean energy, for example, achieve more equitable societies or develop new treatments for cancer and other debilitating diseases.

François-Philippe Champagne, Canada’s minister of innovation, science and industry, announced the chairs at the Canadian Science Policy Conference on Nov. 16, along with funding for a range of research programs and projects across the country – including the containment level 3 lab at U of T's Temerty Faculty of Medicine that enables researchers to study certain high-risk pathogens.

Among the 19 new chairs at U of T is Caroline Hossein, an associate professor in global development studies at U of T Scarborough. Named a tier two chair in Africana development and feminist political economy, Hossein studies “solidarity economies,” a movement that emphasizes social benefit over financial gain. She is writing a book about “rotating savings and credit associations” in Canada. These are small groups of immigrants, usually from Africa and the Caribbean, who often lack access to bank capital and come together to help each other financially.

Scott Gray-Owen, a U of T professor in the department of molecular genetics, was named a new tier one chair in infectious immunopathogenesis. His research aims to understand how pathogens such as bacteria and viruses infect their hosts and evade the immune response. In 2021, Gray-Owen was named the inaugural director of a new, forward-looking initiative at U of T called the Emerging and Pandemic Infections Consortium (EPIC), which seeks to combat new infectious diseases and prevent the rise of future pandemics. In that role, he also oversees U of T’s Combined Containment Level 3 Unit, a biosafety facility at the Temerty Faculty of Medicine that enables researchers to conduct research on certain pathogens.

How cities affect our health is the research interest of Marianne Hatzopoulou, a professor in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering. She was named a new tier one chair in transport decarbonization and air quality. Hatzopoulou creates models of emissions from road transportation and evaluates how this air pollution affects the local population. Not long ago, she was involved in a study that used low-cost sensors to measure carbon monoxide, nitrogen dioxide, coarse particulate matter and other pollutants at nearly 70 sites across Beirut, identifying air pollution hot spots where people were most at risk. She also examined the effects of natural gas fracking in the northeast region of British Columbia. Another study examined the potential improvement in air quality resulting from the widespread adoption of electric vehicles.

Among the U of T faculty whose Canada Research Chairs were renewed is Jean Philippe Julien, senior scientist with the molecular research program of SickKids Research Institute and an associate professor in the department of biochemistry in the Temerty Faculty of Medicine. Julien also received support from the Canada Foundation for Innovation’s John R. Evans Leaders Fund (JELF), which helps provide research infrastructure associated with the Canada Research Chairs program, for his project, “Molecular Biological Systems for the Study of Antibody-Antigen Complexes.” Named for late U of T President Emeritus John R. Evans, the fund helps institutions recruit and retain outstanding researchers and provide them with the necessary tools and technology to perform their work.

(See the full list of new and renewed Canada Research Chairs at U of T)

“I’d like to commend all ��Ƶ researchers who were named new Canada Research Chairs or who had their chair renewed in this latest round,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives.

“The Canada Research Chair program provides critical support for researchers across our three campuses who are generating new knowledge, developing key innovations and helping to address some of the world’s most complex challenges.”

Established in 2000, the Canada Research Chair program invests up to $310 million annually to attract and retain top academic talent in disciplines spanning engineering, the natural sciences, health sciences, humanities and social sciences.

Here is the full list of new and renewed Canada Research Chairs at U of T:

New Canada Research Chairs

Aimy Bazylak in the department of mechanical and industrial engineering in the Faculty of Applied Science & Engineering, Tier 1 in clean energy.

Denise Belsham in the department of physiology in the Temerty Faculty of Medicine, Tier 1 in neuroendocrinology.

Maged Goubran at the Sunnybrook Health Science Centre and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in artificial intelligence and computational neuroscience.

Scott Gray-Owen in the department of molecular genetics in the Temerty Faculty of Medicine, Tier 1 in infectious immunopathogenesis.

Robin Hayeems at the Hospital for Sick Children and the Institute of Health Policy, Management and Evaluation in the Dalla Lana School of Public Health, Tier 2 in genomics and health policy.

Marianne Hatzopoulou in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering, Tier 1 in transport decarbonization and air quality.

Caroline Hossein in the department of global development studies at U of T Scarborough, Tier 2 in Africana development and feminist political economy.

Muhammad Husain at the Centre for Addiction and Mental Health and the department of psychiatry in the Temerty Faculty of Medicine, Tier 2 in treatment innovation in mood disorders.

Courtney Jones at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in leukemia stem cell metabolism.

Andrea Knight at the Hospital for Sick Children and the department of paediatrics in the Temerty Faculty of Medicine, Tier 2 in mental health and chronic disease of childhood.

Sushant Kumar at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in genomic medicine.

J. Rafael Montenegro Burke in the Donnelly Centre in the Temerty Faculty of Medicine, Tier 2 in functional metabolomics and lipidomics.

Deborah O'Connor in the department of nutritional sciences in the Temerty Faculty of Medicine, Tier 1 in human milk and infant nutrition.

Vijay Ramaswamy at the Hospital for Sick Children and the department of paediatrics in the Temerty Faculty of Medicine, Tier 2 in pediatric neuro-oncology.

Gregory Schwartz at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in bioinformatics and computational Biology.

Jay Shaw in the department of physical therapy in the Temerty Faculty of Medicine, Tier 2 in responsible health innovation.

Anastasia Tikhonova at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in stem cell niche biology.

Burton Yang at Sunnybrook Health Sciences Centre and the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine, Tier 1 in cardiac remodeling.

Darren Yuen at Unity Health Toronto and the department of medicine in the Temerty Faculty of Medicine, Tier 2 in fibrotic injury.

Renewed Canada Research Chairs

John Calarco in the department of cell and systems biology in the Faculty of Arts & Science, Tier 2 in neuronal RNA biology.

Myron Cybulsky at the University Health Network and the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine, Tier 1 in arterial wall biology and atherogenesis.

David Duvenaud in the department of computer science in the Faculty of Arts & Science, Tier 2 in generative models.

Julie Forman-Kay in the Hospital for Sick Children and the department of biochemistry in the Temerty Faculty of Medicine, Tier 1 in intrinsically disordered proteins.

Bryan Gaensler in the David A. Dunlap department of astronomy and astrophysics in the Faculty of Arts & Science, Tier 1 in radio astronomy.

Alec Jacobson in the department of computer science in the Faculty of Arts & Science, Tier 2 in geometry processing.

Jean-Philippe Julien at the Hospital for Sick Children and the department of biochemistry in the Temerty Faculty of Medicine, Tier 2 in structural immunology.

Kang Lee in the department of applied psychology and human development at the Ontario Institute for Studies in Education, Tier 1 in moral development and developmental neuroscience.

David Levin in the department of computer science in the Faculty of Arts & Science, Tier 2 in simulation-driven graphics and fabrication.

Jed Meltzer at Baycrest Hospital and the department of psychology in the Faculty of Arts & Science, Tier 2 in interventional cognitive neuroscience.

Sean Mills in the department of history in the Faculty of Arts & Science, Tier 2 in Canadian and transnational history.

Kimberly Pernell-Gallagher in the department of sociology in the Faculty of Arts & Science, Tier 2 in economic sociology.

Arun Ramchandran in the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering, Tier 2 in engineered soft materials and interfaces.

Andras Tilcsik at the Rotman School of Management, Tier 2 in strategy, organizations, and society.

Haley Wyatt in the department of biochemistry in the Temerty Faculty of Medicine, Tier 2 in mechanisms of genome instability.

A new model for innovation? How Elizabeth and Aled Edwards are driving an open science revolution

rahul.kalvapalle — Mon, 07 Nov 2022 15:38:12 +0000

A new model for innovation? How Elizabeth and Aled Edwards are driving an open science revolution

rahul.kalvapalle Mon, 11/07/2022 - 10:38

Cutline

Elizabeth and Aled Edwards say an open science approach promises to accelerate key discoveries that will help address everything from the next pandemic to climate change (photo by Johnny Guatto)

Rahul Kalvapalle

Topic

Open Science

Structural Genomic Consortium

Molecular Genetics

Institutional Strategic Initiatives

When the COVID-19 pandemic struck, scientists, corporations and governments around the world scrambled to share research data and ideas to advance the understanding of the disease and produce life-saving vaccines and therapies in record time.

For many, it was a crash course in “open science” – the practice of freely sharing research information and, often, eschewing intellectual property protections on early-stage inventions for the sake of accelerating discovery.

But for the ��Ƶ’s Elizabeth and Aled Edwards, it was little more than a well-publicized example of an approach for which they’ve long been advocates (and an example Aled argued should have been extended by making access to COVID-19 vaccines more equitable globally). Over the course of their careers, the two researchers – who are married – have attracted numerous industry partners to open science initiatives in medicine (Aled) and engineering (Elizabeth), helping establish U of T as a hotbed of what could be described as a new model of innovation.

Each has been made an Officer of the Order of Canada for their industry partnership work. Elizabeth received the honour in 2020 for her contributions to bioremediation, while Aled was honoured earlier this year for his efforts in advancing Canada as a leader in open science research through his leadership of the Structural Genomics Consortium (SGC), which he founded in 2003.

“Society’s big problems – such as how AI can help drug discovery, how we’re going to create bio-manufacturing capabilities that can provide medicine to the world affordably, how we’re going to tackle climate change and how we prevent the next pandemic – can’t be solved by any single actor,” says Aled, a professor in the departments of medical biophysics and molecular genetics and the Temerty Nexus Chair of Health Innovation and Technology in the Temerty Faculty of Medicine. “They require spaces to focus purely on innovation – the science, engineering and other research – in which ideas are freely shared and worries about patenting are set aside.

“We believe that universities in general, and U of T specifically, are ideally positioned to host these spaces.”

While some critics fear a sharing-first approach will dampen incentives and scare off industry, SGC’s open science policy, which expressly forbids patenting on its research, has so far had precisely the opposite effect. Over the past 15 years, the expansion of SGC’s open science remit has only served to bring more industry partners to the table.

A more recent SGC project – Critical Assessment of Computational Hit-Finding Experiments (CACHE) – was organized with several partners from Big Pharma and aims to accelerate development of AI methods in drug discovery. It invites experts to participate in “challenges” around predicting which small molecules bind to specific target proteins implicated in diseases including Parkinson’s disease and COVID-19, and placing the drug starting points in the public domain. In an interview for the CACHE website, Alexander Hillisch, vice-president and head of computational molecular design at Bayer AG in Wüppertal, Germany – one of the companies supporting CACHE – said the incentive for companies lies in being able to access quality experimental data and get to know the most skilled scientists for potential future collaborations.

Beyond his stewardship of SGC, Aled has founded and led numerous companies including the more traditional Affinium Pharmaceuticals, a venture-backed company that developed and sold a new antibiotic, and the more unusual M4K Pharma, which is developing new, but affordable, therapeutics for rare children’s cancers using an open science business model.

Aled sums it up: “To me, in my work, open science is not an end – it’s a business tactic to reach an end, which is to help us understand more about the human genome and human biology, and to allow this knowledge to be translated as rapidly as possible to drive new treatments.”

Elizabeth, meanwhile, traces her early forays into open science to when she worked with industry partners to develop a microbial culture, KB-1, that can dechlorinate pollutants in groundwater. That invention led to the creation of the spinoff company SiREM.

Since KB-1 was a collaborative discovery, patenting it became more of a headache than it was worth.

“When we started working together, we weren’t thinking about IP – it wasn’t even on the radar,” says Elizabeth, a University Professor in the department of chemical engineering and applied chemistry in the Faculty of Applied Sciences & Engineering who is cross-appointed to the department of cell and systems biology in the Faculty of Arts & Science.

“So, we just negotiated a royalty and have kept working together ever since, with students going back and forth.”

KB-1 has since been deployed at some 900 sites around the world by organizations ranging from Fortune 500 companies to NASA, with SiREM continuing to collaborate with Elizabeth and her students to develop cultures that can degrade other contaminants.

Elizabeth Edwards gives a tour of U of T’s BioZone research centre, which has freely disseminated nearly all of its research (photo by Nick Iwanyshyn)

Elizabeth is also the founding director of BioZone, an interdisciplinary research centre that is dedicated to developing biotechnologies that address sustainability challenges. Nearly all of of BioZone’s past research output has been disseminated freely, and all new industry partnerships are being pursued using the no-patent, open science approach – including Elements of Bio-Mining, which aims to harness microbial science to stabilize waste tailings from mining. Industry partners include mining giant Vale and commodity trader Glencore.

The U of T open science industry partnership roadmap is also driving similar projects across Canada. That includes “Open Plastic,” led by Queen’s University assistant professor and U of T alumnus Laurence Yang, which focuses on the discovery of enzymes that can break down plastics in the environment – and has attracted partners including chemicals giant DuPont; Star Produce, a distributor of fruits and vegetables; and Carbios, the first industrial-scale foray into enzymatic PET recycling.

Elizabeth says the long list of corporate partners that have collaborated on open science ventures proves that IP isn’t the main motivating factor for companies looking to work with universities. With the help of student interns from the Faculty of Law, Elizabeth, Aled and colleagues at BioZone rebutted common misconceptions about industry partnerships in an article titled “Could open science stimulate industry partnerships in chemical engineering university research?” published in the Canadian Journal of Chemical Engineering.

“The people who work in companies read the same literature as professors do, and they’re just as smart and capable – but they have a different mandate,” she says.

“If something interesting happens in their labs but it’s a little bit sideways, they’re not allowed to pursue it because they have a core business to stick to. So, these companies love [open science partnerships] because it helps them find out more about the things they wish they could do, but don’t have time for.”

Aled agrees.

“Industry loves the clarity of the policy; they know exactly what they’re going into the collaboration for – to talk science, to engage with brilliant young people, to do science they would not have the time to do internally, and to get excited about the latest scientific developments,” he says.

“Elizabeth and I see the university’s role in the innovation economy as being a vehicle for industry to ask far-out questions, while allowing them a way to engage and attract students to their problems – and students really enjoy tackling real-world problems.”

He adds that U of T’s support of his and Elizabeth’s open science initiatives has placed the university in a leadership position in industry engagement worldwide.

“In supporting us to explore this radical way to innovate, U of T has painted a picture of how the Canadian university of the future can work with the private sector and others to tackle big problems and more effectively move ideas from the lab to the market.

“It’s an innovation on innovation, and we hope U of T continues to lead the way.”

Good for you, better for the planet: U of T cyclists pedal toward a more sustainable future

Christopher.Sorensen — Thu, 20 Oct 2022 20:13:42 +0000

Good for you, better for the planet: U of T cyclists pedal toward a more sustainable future

Christopher.Sorensen Thu, 10/20/2022 - 16:13

Cutline

Beth Austerberry, executive director of Bikechain, helps Walid Maraqa, a grad student in biostatistics, perform basic maintenance on his bike (photo by Geoffrey Vendeville)

Mariam Matti

Topic

City & Culture

Climate Positive Energy

Cycling