Research &amp; Innovation

Subheadline

The National Taiwan University ranking evaluates universities based on research output and impact

The ��Ƶ climbed one spot to fourth place globally in the latest National Taiwan University ranking, which evaluates universities based on their research output and impact.

U of T’s strong performance in the 2024 edition of the NTU World University Rankings, released this week, puts it in elite global company. The four other schools in the top five were Harvard University, Stanford University, University College London and the University of Oxford.

Among public universities, U of T placed second globally and first in North America.

“This ranking is yet another reminder that the research produced at the ��Ƶ is truly world-class,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives.

“It also reflects our reputation for research excellence and impact across a broad range of fields – from medicine to the social sciences.”

The NTU ranking analyzes scholarly papers and research citations, scoring each institution based on productivity, impact and excellence. The top 1,000 universities were ranked this year with more than 1,500 considered.

In addition to the overall ranking, NTU ranked universities by six broad fields and 27 specific subjects.

U of T ranked among the top 50 institutions worldwide – and first in Canada – in four of the six broad fields. Notably, that includes a rank of second globally in medicine, the same as last year, and third globally in social sciences – up three spots.

U of T also ranked among the top 10 universities globally in five subject categories: clinical medicine (second), neurosciences and behaviour (third), social sciences (third), psychiatry and psychology (fourth) and biology and biochemistry (sixth).

Two other Canadian universities made the top 100 in the main NTU ranking: University of British Columbia (37th) and McGill University (57th).

Overall, U of T continues to be the highest-ranked Canadian university and one of the top-ranked public universities in the five most closely watched international rankings: Times Higher Education’s World University Rankings, QS World University Rankings, ShanghaiRanking Consultancy’s Academic Ranking of World Universities, U.S. News & World Report’s Best Global Universities and National Taiwan University World University Rankings.

Research team explores next-gen vaccines to guard against sexually transmitted infections

Christopher.Sorensen — Wed, 04 Sep 2024 16:07:53 +0000

Research team explores next-gen vaccines to guard against sexually transmitted infections

Christopher.Sorensen Wed, 09/04/2024 - 12:07

Cutline

Aereas Aung, an assistant professor in the Institute of Biomedical Engineering , is developing new tools to study and manipulate immune cells and their reaction to vaccines (photo by Tim Fraser)

Qin Dai

Topic

Institute of Biomedical Engineering

Connaught Fund

Vaccines

Subheadline

"This work could lay the foundation for more effective vaccines that curb the spread of STIs, particularly in marginalized communities disproportionately affected by these diseases”

A research team from the ��Ƶ is creating a new generation of vaccines that aims to overcome key hurdles faced by some existing formulations.

For example, a common shortcoming of many traditional vaccines is that they can’t produce antibodies in tissues where sexually transmitted infections (STIs) often enter the body.

“Most current vaccines fail to produce sufficient antibodies within mucosal tissues, leaving a significant gap in our defense against sexually transmitted infections,” says Aereas Aung, an assistant professor at the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering who is leading the research effort.

“Our goal is to develop a novel strategy that leverages the strengths of parenteral vaccination while also targeting the mucosal immune system.”

Normally vaccines are injected parenterally, meaning it is injected into or under the skin, into the muscle or directly into the bloodstream. The vaccine then travels to lymph nodes, which are small glands that help produce antibodies. Mucosal tissues in the cervix and rectum present a unique challenge since the mucus in these areas can break down the vaccine quickly and wash it away, making it difficult to reach the lymph nodes and be effective.

Aung’s research proposes fusing a protein carrier to the disease antigens, allowing it to reach distant mucosal lymph nodes after injection.

“We aim to incorporate potent immunostimulatory components into our antigen construct, optimizing its distribution and enhancing mucosal antibody responses,” says Aung.

“If successful, this work could lay the foundation for more effective vaccines that curb the spread of STIs, particularly in marginalized communities disproportionately affected by these diseases.”

Aung’s project is one of 51 U of T faculty members whose work is being supported by the Connaught New Researcher Awards in the most recent round – and one of eight at U of T Engineering. The award helps early-career faculty members establish their research programs.

The other U of T Engineering researchers whose projects are supported by the award are: 

Mohammed Basheer, department of civil and mineral engineering – Integrated hydrological-statistical method and tool for landslide susceptibility mapping in a changing climate
Daniel Franklin, Institute of Biomedical Engineering – Development of equitable pulse oximeters
Sarah Haines, department of civil and mineral engineering – Open Plenums & Indoor Environments (OPEN): Evaluating the impact of return air systems on indoor environmental quality
Mark Jeffrey, Edward S. Rogers Sr. department of electrical and computer engineering – Productively surmounting the memory wall with task parallelism
Caitlin Maikawa, Institute of Biomedical Engineering – Affinity-directed dynamic polymer materials for biomarker sensing
Mohamad Moosavi, department of chemical engineering and applied chemistry – Learning the Language of Metal-Organic Frameworks Topology
Cindy Rottmann, Institute for Studies in Transdisciplinary Engineering Education and Practice (ISTEP) – But I could be fired! How early career engineers hold the public paramount from organizationally subordinate locations

Virtual and augmented reality can temporarily change the way people perceive distances: Study

Christopher.Sorensen — Fri, 30 Aug 2024 17:23:24 +0000

Virtual and augmented reality can temporarily change the way people perceive distances: Study

Christopher.Sorensen Fri, 08/30/2024 - 13:23

Cutline

U of T researchers found that people moved differently in virtual reality and augmented reality, and that these changes led to temporary movement errors in the real world (photo by D-BASE/Getty Images)

Jelena Damjanovic

Topic

Faculty of Kinesiology & Physical Education

Virtual Reality

Subheadline

'We wanted to understand if the way our brains and bodies adapt to these digital environments changes how accurately we can move and interact with real objects"

Researchers at the ��Ƶ have found that using virtual and augmented reality (VR and AR) can temporarily change the way people perceive and interact with the real world – with potential implications for the growing number of industries that use these technologies for training purposes.

The study, published recently in the journal Scientific Reports, not only found that people moved differently in VR and AR, but that these changes led to temporary errors in movement in the real world. In particular, participants who used VR tended to undershoot their targets by not reaching far enough, while those who used AR tended to overshoot their targets by reaching too far.

This effect was noticeable immediately after using VR or AR, but gradually disappeared as participants readjusted to real-world conditions.

“Our study explored how using mixed reality (MR) technologies, like virtual reality and augmented reality, affects our ability to perform everyday physical tasks once we return to the real world,” says Xiaoye Michael Wang, a research associate in the Faculty of Kinesiology & Physical Education who co-authored the study with Professor Tim Welsh.

“Specifically, we wanted to understand if the way our brains and bodies adapt to these digital environments changes how accurately we can move and interact with real objects after using VR and AR.”

Research associate Xiaoye Michael Wang fits a VR display onto study participant Colin Dolynski (photo by Molly Brillinger)

The researchers say they were surprised by two findings: first, that movement patterns in VR and AR transfer to real-world movements; and second, by how quickly the effects of AR wore off compared to VR, with study participants readjusting to real-world conditions faster after using AR.

The difference between VR and AR, they suggest, might be because people in AR can still see and interact with their actual surroundings, which helps them maintain a more accurate sense of depth and distance.

“These findings are crucial because they highlight a potential challenge in transferring skills learned in VR or AR to the real world,” says Welsh. “As more industries and training programs adopt these technologies for skill development, it's important to understand how they might affect real-world performance.

“For example, this could be relevant for training surgeons, pilots or even everyday skills like driving. Knowing the limitations and effects of VR and AR helps ensure these technologies are used effectively and safely.”

The researchers will next be exploring how different types of VR and AR experiences, like those involving more complex or immersive scenarios, affect real-world performance. They’re also interested in seeing how training duration and individual differences such as prior experience with these technologies, influence adaptation and readjustment.

“This research will help us better understand how to design VR and AR systems that minimize negative after-effects and maximize their potential for training and skill development,” Wang says.

U of T researchers integrate crucial immune cells onto heart-on-a-chip platform

Christopher.Sorensen — Fri, 23 Aug 2024 12:56:51 +0000

U of T researchers integrate crucial immune cells onto heart-on-a-chip platform

Christopher.Sorensen Fri, 08/23/2024 - 08:56

Cutline

L-R: U of T post-doctoral fellow Shira Landau, PhD alum Yimu Zhao and Professor Milica Radisic are three of the primary authors of a study that could lead to advancements in the creation of more stable and functional heart tissues (supplied images)

Qin Dai

Topic

Institute of Biomedical Engineering

Toronto General Hospital

Donnelly Centre for Cellular & Biomolecular Research

University Health Network

Subheadline

The immune cells, known as primitive macrophages, were found to enhance heart tissue function and vessel stability

Researchers at the ��Ƶ have discovered a novel method for incorporating primitive macrophages – crucial immune cells – into heart-on-a-chip technology, in a potentially transformative step forward in drug testing and heart disease modeling.

In a study published in Cell Stem Cell, an interdisciplinary team of scientists describe how they integrated the macrophages – which were derived from human stem cells and resemble those found in the early stages of heart development – onto the platforms. These macrophages are known to have remarkable abilities in promoting vascularization and enhancing tissue stability.

Corresponding author Milica Radisic, a senior scientist in the University Health Network's Toronto General Hospital Research Institute and professor in the Institute of Biomedical Engineering at U of T’s Faculty of Applied Science & Engineering, says the approach promises to enhance the functionality and stability of engineered heart tissues.

“We demonstrated here that stable vascularization of a heart tissue in vitro requires contributions from immune cells, specifically macrophages. We followed a biomimetic approach, re-establishing the key constituents of a cardiac niche,” says Radisic, who holds a Canada Research Chair in Functional Cardiovascular Tissue Engineering

“By combining cardiomyocytes, stromal cells, endothelial cells and macrophages, we enabled appropriate cell-to-cell crosstalk such as in the native heart muscle.”

Professor Milica Radisic's research team have worked on developing a miniaturized version of cardiac tissue on heart-on-a-chip platforms for a decade (photo by Nick Iwanyshyn)

A major challenge in creating bioengineered heart tissue is achieving a stable and functional network of blood vessels. Traditional methods have struggled to maintain these vascular networks over extended periods, limiting their effectiveness for long-term studies and applications.

In their study, researchers demonstrated that the primitive macrophages could create stable, perfusable microvascular networks within the cardiac tissue, a feat that had previously been difficult to achieve.

Furthermore, the macrophages helped reduce tissue damage by mitigating cytotoxic effects, thereby improving the overall health and functionality of the engineered tissues.

“The inclusion of primitive macrophages significantly improved the function of cardiac tissues, making them more stable and effective for longer periods,” says Shira Landau, a post-doctoral fellow in Radisic’s lab and one of the study’s lead authors.

The breakthrough has far-reaching implications for the field of cardiac research. By enabling the creation of more stable and functional heart tissues, researchers can better study heart diseases and test new drugs in a controlled environment.

Researchers say this technology could lead to more accurate disease models and more effective treatments for heart conditions.

Healthy aging in place: New pilot program to provide high-tech cognitive, physical enrichment for seniors

rahul.kalvapalle — Thu, 22 Aug 2024 13:32:02 +0000

Healthy aging in place: New pilot program to provide high-tech cognitive, physical enrichment for seniors

rahul.kalvapalle Thu, 08/22/2024 - 09:32

Cutline

2RaceWithMe, a tool developed by Professor Mark Chignell from the department of mechanical and industrial engineering in U of T's Faculty of Applied Science & Engineering, combines physical and cognitive engagement by requiring users to pedal to be able to watch scenic videos (photo by Justin Greaves/Centivizer)

Safa Jinje

Topic

Our Community

department of mechanical and industrial engineering

Institutional Strategic Initiatives

Connaught Fund

Subheadline

The initiative, supported by a Connaught Community Partnership Research Program award, explores the use of interactive tools to promote active lifestyles among older adults

Older adults living in a Toronto co-operative apartment building will soon have access to high-tech activity spaces designed to promote cognitive, physical and social enrichment, thanks to a new pilot project led by the ��Ƶ’s Mark Chignell.

The activity spaces aim to promote healthy aging for older adults who are aging in place – meaning they have the social and health supports to live safely and independently. They will be located in the communal area of a City Park co-op building that is considered a naturally occurring retirement community, where more than 30 per cent of occupants are over the age of 65.

The initiative was launched by Chignell, a professor in the department of mechanical and industrial engineering in U of T’s Faculty of Applied Science & Engineering, in collaboration with HelpAge Canada, a non-profit that supports community-based services for seniors, and AGE-WELL, a research network and U of T institutional strategic initiative.

It’s one of nine projects to be supported by 2024-25 Community Partnership Research Program awards, given by U of T’s Connaught Fund with the aim of accelerating research carried out in collaboration with community partners and driven by their needs and priorities.

“My work is motivated by the fact that physical and cognitive health can decline very quickly for older adults,” says Chignell.

“We know the physical body and brain work together, and that physical exercise is important for cognitive status and preventing dementia. So being able to promote more active lifestyles for people who are still living independently in the community can have an immense benefit for our society.”

The activity spaces will feature products from Centivizer, a U of T startup spun off from Chignell’s research, that specializes in creating interactive activities, games and cognitive assessment tools to support healthy aging.

These include 2RaceWithMe, a device that promotes both physical and cognitive engagement by having users pedal while watching scenic videos that only play when the pedals are in motion.

Centivizer has also developed a suite of whack-a-mole-style games for cognitive assessment that Chignell hopes can be used to promote cognitive safety in clinical practice.

A two-time recipient of Connaught Innovation Awards, Chignell says he feels honoured to now receive support from the Connaught Fund's Community Partnership Research Program.

“The Connaught is a great validation as I start this project in naturally occurring retirement communities,” says Chignell. “I am also continuing to work with retirement homes and long-term care centres, including a new collaboration with a long-term care home in Tokyo, Japan.

“I’m hoping that this project will demonstrate the value of using our products in the community to help older people retain their physical and cognitive abilities for longer.”

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle — Tue, 20 Aug 2024 16:17:45 +0000

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle Tue, 08/20/2024 - 12:17

Cutline

The "SynNeurGe" classification system for Parkinson's disease, proposed by researchers led by Professor Anthony Lang of the University Health Network and U of T, is based on three key biomarkers (photo by FG Trade/Getty Images)

Eileen Hoftyzer

Topic

Department of Medicine

Tanz Centre for Research in Neurodegenerative Diseases

Parkinson's

University Health Network

Subheadline

The classification system could enable advancements in the development of tailored treatments for Parkinson's disease

A team of researchers led by Anthony Lang of the University Health Network and the ��Ƶ have proposed a novel classification system for Parkinson’s disease that considers biological features and not just clinical symptoms.

The "SynNeurGe" system, described by Lang and collaborators in a paper published in The Lancet Neurology, classifies Parkinson’s disease based on three biomarkers: presence or absence of misfolded alpha synuclein protein, which is believed to cause or contribute to the underlying neurodegeneration; evidence of neurodegeneration using imaging techniques; and presence of gene variants that increase disease risk.

The researchers argue that such a classification system is necessary to advance the development of tailored treatments for Parkinson’s disease.

Professor Anthony Lang (supplied image)

“This is a complex group of disorders that may cause similar symptoms, but biologically they're very different,” says Lang, a senior scientist and Lily Safra Chair in Movement Disorders at UHN and a professor in the department of medicine and the Tanz Centre for Research in Neurodegenerative Disease at U of T’s Temerty Faculty of Medicine, where he holds the Jack Clark Chair for Parkinson’s Disease Research

“If we cannot find ways to subdivide patients biologically, then applying a therapy designed to affect one biological pathway may not be effective in another group of patients that doesn't have that same pathway involved – and we won’t really have precision or personalized medicine for Parkinson’s disease.”

Currently, Parkinson’s disease is classified based on clinical presentation and symptoms, but the disease can affect the brain for years, possibly even decades, before symptoms appear. For future therapies to treat the underlying disease rather than just the symptoms, patients will need early intervention and treatments tailored to the biological features of the disease, researchers say.

Similar approaches are being used for other diseases – cancer treatments vary not only by the location of tumors but also their molecular features, and the development of drugs for Alzheimer’s disease is increasingly guided by the specific biological mechanisms involved in the disease.

The SynNeurGe classification system, while based on the three key biomarkers, also considers whether clinical features are present. The different combinations of biomarkers classify the disease into various sub-types.

Lang and co-authors note that such a classification should only be used for research at present, although it will almost certainly have clinical applications.

“Eventually we will see a biological approach influencing clinical care, particularly when we finally have effective disease-modifying therapies,” says Lang. “We currently don’t know how important these biomarkers actually are.

"We need large-scale prospective studies of biomarkers, imaging and clinical features to interpret the results, give patients accurate information about their diagnosis and provide appropriate treatment.”

Lang’s team plans to start conducting such studies of cerebrospinal fluid, skin and blood to look for biomarkers of different sub-types of Parkinson’s disease that will help inform the classification system and the development of tailored therapies.

“Now is the time to think about these diseases not solely based on their clinical manifestations, but to look at the biology and try to separate different biological subtypes so we can ultimately improve treatment for this disease,” Lang says.

Professor Graham Collingridge, director of the Tanz Centre, says Lang and his team’s “landmark paper” is poised to have a significant impact on clinical practice around Parkinson's. “I am delighted that our researchers have played such a key role in this important biological classification,” Collingridge says.

Lang says research by Tanz Centre scholars has contributed significantly to the body of knowledge used to develop the proposed biological classification.

For example, Professor Ekaterina Rogaeva’s research on the genetics and epigenetics of Parkinson’s disease has shown that multiple genes and environments can influence Parkinson’s risk, highlighting the need to tailor therapies based on a patient’s genetic makeup.

Other researchers – including Anurag Tandon, Joel Watts, Martin Ingelsson and Gabor Kovacs – have been studying the role of misfolded alpha synuclein in neurodegeneration as well as cases of Parkinson’s disease where alpha synuclein is absent – which informed how Lang’s team included the protein in the classification.

U of T startup Honeybee acquired by global clinical trials firm Leapcure

rahul.kalvapalle — Fri, 16 Aug 2024 14:55:48 +0000

U of T startup Honeybee acquired by global clinical trials firm Leapcure

rahul.kalvapalle Fri, 08/16/2024 - 10:55

Cutline

(photo courtesy of Leapcure)

Rahul Kalvapalle

Topic

Our Community

U of T Entrepreneurship

Innovation & Entrepreneurship

Health Innovation Hub

Impact Centre

ONRamp

Startups

Subheadline

Co-founded by Catherine Chan and Weiwei Li, Honeybee Trials' platform helps clinical trial recruiters find, screen and manage patients for their research

Honeybee Trials, a ��Ƶ startup that connects research teams with patients and study participants, has been acquired by global clinical trials company Leapcure in a deal that is poised to drive more inclusive and affordable trials that’s ultimately applicable to a broader population.

Co-founded by U of T alumni Catherine Chan and Weiwei Li, Honeybee built a web and mobile platform to help clinical trial teams attract, screen, recruit and manage study participants. Since its founding in 2019, the startup has connected over 30,000 patients and participants to more than 1,000 clinical trials across North America.

Leapcure, headquartered in California, offers an array of solutions that combines people-backed services with data-driven technologies to fill clinical trials for global sponsors and CROs, but can now expand affordable patient recruitment to institutional sites, private sites and biotech firms. Moreover, their work alongside patients and advocacy groups has significantly helped to reach underrepresented communities – a focus that will receive a boost following the purchase of Honeybee.

Chan, who earned a master’s degree in the Temerty Faculty of Medicine’s department of nutritional sciences, says the deal grew out of a desire to partner strategically with a larger company that could provide access to broader sectors within the clinical research world.

Catherine Chan (L) and Weiwei Li (supplied image)

“At Honeybee, we offered competitive pricing for academic and hospital sites, local CROs [contract research organizations] and biotech firms,” Chan says. “With this partnership, we’re able to provide services across all of the different types of trial scopes and sizes.”

She adds that both Honeybee and Leapcure have placed a strong focus on diversity, equity, inclusion and accessibility by helping researchers attract study participants of different ethnicities, ages, genders and sexual orientations – helping make clinical trials more equitable and reflective of the wider population.

“It’s important to us that there's a mission and vision alignment between the companies... it couldn’t be a better fit,” Chan said.

The asset purchase deal for an undisclosed amount, which was announced in an Aug. 13 press release, will see Chan transition from CEO of Honeybee to senior director of product at Leapcure.

“We’re excited to join forces with Catherine and Honeybee. They’ve been really focused on the newest recruitment technologies that are most impactful for both patients and research,” said Leapcure CEO Zachary Gobst. “A big reason that things came together was our alignment on impact first. It’s a credit to how they’ve been approaching their business the right way from the beginning."

Honeybee evolved out of the frustrations that Chan faced in recruiting study participants for her master’s thesis. Motivated to explore solutions, Chan created a prototype that would help match participants with trials; she then enrolled in a one-week accelerator program in the Impact Centre (now the Centre for Entrepreneurship) in the Faculty of Arts & Science.

She soon teamed up with Li, who earned his bachelor’s and master’s of applied science degrees from the Faculty of Applied Science & Engineering, to co-found Honeybee. The startup later joined the Health Innovation Hub (H2i) accelerator and operated out of office space in U of T Entrepreneurship’s ONRamp facility prior to the COVID-19 pandemic.

With COVID-19 measures encouraging the adoption of digital tools by clinical research teams, Honeybee found itself well-placed to play an important role. “The pandemic provided an opportunity for many tech companies to scale as the market became more open-minded and ready to adopt technologies to help connect them day-to-day," Chan says. "We saw a rapid adoption of Honeybee’s technology during this time where people moved away from traditional recruitment and patient communications to the current age.

“Although digital adoption across other industries has grown quite rapidly, healthcare has lagged behind, rightfully so and for many reasons, but we’re glad the transformation is happening. Just five years ago, clinical trial coordinators were still using paper handouts to recruit on the street and paper calendars to schedule patients.

“The pandemic expedited researchers being able to meet people where they are.”

Chan says the acquisition by Leapcure will enable the rollout of tiered services ranging from low-cost, self-serve tiers – targeting research teams with more modest budgets – to higher levels of service that include dedicated management.

“I’m really excited about the solutions we now have to offer together as well as the next steps in how we’re going to disrupt clinical trials.”

Professor Paul Santerre, co-founder and director of H2i, hailed Chan as "a model outcome" of the accelerator's mission to empower innovators in translating their ideas into products and companies that tackle important problems.

“Catherine and her team’s achievements are transformative in terms of democratizing the recruitment of patients for clinical study cohorts," said Santerre, the Baxter Chair for Health Technology and Commercialization at the University Health Network and professor in the Faculty of Dentistry and Institute of Biomedical Engineering who is cross-appointed to the department of chemical engineering and applied chemistry.

"She has much to still teach us about the power of digital tools and their ethical use to achieve impact in clinical research trials – and this acquisition will accelerate that outcome."

U of T researchers develop AI model to predict 'very dynamic' peptide structures

Christopher.Sorensen — Thu, 15 Aug 2024 12:54:41 +0000

U of T researchers develop AI model to predict 'very dynamic' peptide structures

Christopher.Sorensen Thu, 08/15/2024 - 08:54

Cutline

PhD Graduate Osama Abdin and Professor Philip M. Kim developed a deep-learning model that can predict all possible shapes of peptides, which are are of keen interest to researchers who are developing therapeutics (supplied image)

Anika Hazra

Topic

Donnelly Centre for Cellular & Biomolecular Research

Alumni

Artificial Intelligence

Computer Science

Subheadline

The new model expands on the capabilities of Google DeepMind's AlphaFold, the leading AI system for predicting protein structures

Researchers at the ��Ƶ have developed a deep-learning model that can predict all possible shapes of peptides – chains of amino acids that are shorter than proteins, but perform similar biological functions.

Called PepFlow, the model combines machine learning and physics to model the range of folding patterns that a peptide can assume based on its energy landscape.

Peptides, unlike proteins, are dynamic molecules that can take on a range of conformations. They are involved in many biological processes that are of keen interest to researchers who are developing therapeutics.

“We haven’t been able to model the full range of conformations for peptides until now,” said Osama Abdin, first author on the study and recent PhD graduate of molecular genetics at U of T’s Donnelly Centre for Cellular and Biomolecular Research. “PepFlow leverages deep-learning to capture the precise and accurate conformations of a peptide within minutes.

“There’s potential with this model to inform drug development through the design of peptides that act as binders.”

The study was recently published in the journal Nature Machine Intelligence.

A peptide’s role in the human body is directly linked to how it folds since its 3D structure determines the way it binds and interacts with other molecules.

“Peptides were the focus of the PepFlow model because they are very important biological molecules and they are naturally very dynamic, so we need to model their different conformations to understand their function,” said Philip M. Kim, the study’s principal investigator and a professor at the Donnelly Centre. “They’re also important as therapeutics, as can be seen by the GLP1 analogues, like Ozempic, used to treat diabetes and obesity.”

Peptides are also cheaper to produce than their larger protein counterparts, said Kim, who is also a professor of computer science in U of T’s Faculty of Arts & Science and a professor of molecular genetics in the Temerty Faculty of Medicine.

The new model expands on the capabilities of AlphaFold, the leading Google DeepMind AI system for predicting protein structure. It does this by generating a range of conformations for a given peptide. Taking inspiration from highly advanced physics-based machine learning models, PepFlow can also model peptide structures that take on unusual formations, including the ring-like structure that results from a process called macrocyclization. Peptide macrocycles are currently a highly promising venue for drug development.

“It took two-and-a-half years to develop PepFlow and one month to train it, but it was worthwhile to move to the next frontier beyond models that only predict one structure of a peptide,” Abdin said.

There are, however, limitations given that PepFlow represents the first version of a new model. The study authors noted a number of ways in which PepFlow could be improved, including training the model with explicit data for solvent atoms, which would dissolve the peptides to form a solution, and for constraints on the distance between atoms in ring-like structures.

Yet, even as a first version, the researchers say PepFlow is a comprehensive and efficient model with potential for furthering the development of treatments that depend on peptide binding to activate or inhibit biological processes.

“Modelling with PepFlow offers insight into the real energy landscape of peptides,” said Abdin.

The research was supported by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.

Common antibiotics carry small but serious risks of life-threatening drug reactions: Study

Christopher.Sorensen — Wed, 14 Aug 2024 12:51:57 +0000

Common antibiotics carry small but serious risks of life-threatening drug reactions: Study

Christopher.Sorensen Wed, 08/14/2024 - 08:51

Cutline

(photo by vorDa/Getty Images)

Misty Pratt

Topic

Sunnybrook Health Sciences