Resarch & Innovation

Researchers at the �ؿ�ζSM and partner hospitals have discovered a DNA repair mechanism that advances understanding of how human cells stay healthy – a finding that could lead to new treatments for cancer and premature aging.

The study, published in the journal Nature Structural and Molecular Biology, also sheds light on the mechanism of action of some existing chemotherapy drugs.

“We think this research solves the mystery of how DNA double-strand breaks and the nuclear envelope connect for repair in human cells,” said Karim Mekhail, co-principal investigator on the study and a professor of laboratory medicine and pathobiology in U of T’s Temerty Faculty of Medicine.

“It also makes many previously published discoveries in other organisms applicable in the context of human DNA repair, which should help science move even faster.”

DNA double-strand breaks arise when cells are exposed to radiation and chemicals, and through internal processes such as DNA replication. They are one of the most serious types of DNA damage because they can stall cell growth or put it in overdrive, promoting aging and cancer.

The new discovery, made in human cells and in collaboration with Razqallah Hakem – a senior scientist at UHN’s Princess Margaret Cancer Centre, University Health Network, and a professor in Temerty Medicine’s department of medical biophysics and department of laboratory medicine and pathobiology – extends prior research on DNA damage in yeast by Mekhail and other scientists.

In 2015, Mekhail and collaborators showed how motor proteins deep inside the nucleus of yeast cells transport double-strand breaks to “DNA hospital-like” protein complexes embedded in the nuclear envelope at the edge of the nucleus.

Other studies uncovered related mechanisms during DNA repair in flies and other organisms. However, scientists exploring similar mechanisms in human and other mammalian cells reported little to no DNA mobility for most breaks.

“We knew that nuclear envelope proteins were important for DNA repair across most of these organisms, so we wondered how to explain the limited mobility of damaged DNA in mammalian cells,” Mekhail says.

The answer is both surprising and elegant.

When DNA inside the nucleus of a human cell is damaged, a specific network of microtubule filaments forms in the cytoplasm around the nucleus and pushes on the nuclear envelope. This prompts the formation of tiny tubes, or tubules, which reach into the nucleus and catch most double-strand breaks.

“It’s like fingers pushing on a balloon,” says Mekhail. “When you squeeze a balloon, your fingers form tunnels in its structure, which forces some parts of the balloon’s exterior inside itself.”

Further research by the study authors detailed several aspects of this process. Enzymes called DNA damage response kinases and tubulin acetyltransferase are the master regulators of the process, and promote the formation of the tubules.

Enzymes deposit a chemical mark on a specific part of the microtubule filaments, which causes them to recruit tiny motor proteins and push on the nuclear envelope. Consequently, the repair-promoting protein complexes push the envelope deep into the nucleus, creating bridges to the DNA breaks.

“This ensures that the nucleus undergoes a form of reversible metamorphosis, allowing the envelope to temporarily infiltrate DNA throughout the nucleus, capturing and reconnecting broken DNA,” says Mekhail.

The findings have significant implications for some cancer treatments.

Normal cells use the nuclear envelope tubules to repair DNA, but cancer cells appear to need them more. To explore the mechanism's potential impact, the team analyzed data representing over 8,500 patients with various cancers. The need was visible in several cancers, including triple-negative breast cancer, which is highly aggressive.

“There is a huge effort to identify new therapeutic avenues for cancer patients, and this discovery is a big step forward,” says Hakem.

“Until now, scientists were unclear as to the relative impact of the nuclear envelope in the repair of damaged DNA in human cells. Our collaboration revealed that targeting factors that modulate the nuclear envelope for damaged DNA repair effectively restrains breast cancer development,” Hakem says.

In the aggressive triple-negative breast cancer, there are elevated levels of the tubules – likely because they have more DNA damage than normal cells. When the researchers knocked out the genes needed to control the tubules, cancer cells were less able to form tumours.

One medication used to treat triple-negative breast cancer is a class of drugs called PARP inhibitors. PARP is an enzyme that binds to damaged DNA and helps repair it. PARP inhibitors block the enzyme from performing repair, preventing the ends of a DNA double-strand break in cancer cells from reconnecting to one another.

The cancer cells end up joining two broken ends that are not part of the same pair. As more mismatched pairs are created, the resulting DNA structures become impossible for cells to copy and divide.

“Our study shows that the drug’s ability to trigger these mismatches relies on the tubules. When fewer tubules are present, cancer cells are more resistant to PARP inhibitors,” says Hakem.

Mekhail says the work underscores the importance of cross-disciplinary collaboration.

“The brain power behind every project is crucial. Every team member counts. Also, every right collaborator added to the research project is akin to earning another doctorate in a new specialty – it’s powerful,” he says.

Mekhail notes the discovery is also relevant to premature aging conditions like progeria. The rare genetic condition causes rapid aging within the first two decades of life, commonly leading to early death.

Progeria is linked to a gene coding for lamin A. Mutations in this gene reduce the rigidity of the nuclear envelope. The team found that expression of mutant lamin A is sufficient to induce the tubules, which DNA damaging agents further boosted. The team thinks that even weak pressure on the nuclear envelope spurs the creation of tubules in premature aging cells.

The findings suggest that in progeria, DNA repair may be compromised by the presence of too many or poorly regulated tubules. The study results also have implications for many other clinical conditions, Mekhail says.

“It’s exciting to think about where these findings will lead us next,” says Mekhail. “We have excellent colleagues and incredible trainees here at Temerty Medicine and in our partner hospitals. We’re already working toward following this discovery and using our work to create novel therapeutics.”

The research was supported by the Canadian Institutes of Health Research, Royal Society of Canada, U of T and Princess Margaret Hospital.

U of T researchers create more efficient perovskite solar cell

Christopher.Sorensen — Wed, 12 Apr 2023 15:22:11 +0000

U of T researchers create more efficient perovskite solar cell

Christopher.Sorensen Wed, 04/12/2023 - 11:22

Cutline

From left Leiwei Zeng, Zaiwei Wang and Hao Chen show off samples of triple-junction perovskite solar cells that boast record gains in efficiency (photo by Tyler Irving)

Tyler Irving

Topic

Breaking Research

Resarch & Innovation

Electrical & Computer Engineering

Faculty of Applied Science & Engineering

Solar

Solar Cells

Sustainability

A team of researchers from the �ؿ�ζSM has created a triple-junction perovskite solar cell with record efficiency by overcoming a key limitation of previous designs.

The prototype represents a significant advance in the development of low-cost alternatives to silicon-based solar cells, which are the current industry standard.

“In addition to lower manufacturing cost, perovskites offer us the ability to stack multiple layers of light-absorbing materials on top of each other, and even on top of traditional silicon cells,” says Professor Ted Sargent, who recently joined the department of chemistry and the department of electrical and computer engineering at Northwestern University but maintains his lab at U of T’s Faculty of Applied Science & Engineering.

“In this work, we used rational design to address a critical challenge that can arise in this multi-layered paradigm, improving both efficiency and durability.”

Today’s solar cells are made from a single wafer of ultra-pure silicon, which is energy-intensive to produce. By contrast, perovskite solar cells are made using perovskite polycrystalline films that are coated onto surfaces with low-cost, solution-processing techniques similar to those used in the printing industry.

By varying the composition of the perovskite crystals within these films, each layer can be “tuned” to absorb different wavelengths of light, making efficient use of the entire solar spectrum. This is not possible with silicon, which always absorbs the same wavelengths.

Sargent’s group is among those developing new ways to unlock the potential of perovskite solar cells. Their previous work has included two-layered tandem cells, but their latest study, published in Nature, focuses on a three-layer design.

“Multi-layered cells are typically designed so that the top layer with wide-bandgap perovskites absorbs the most energetic photons, meaning high-frequency light with short wavelengths, toward the violet end of the spectrum,” says post-doctoral researcher Zaiwei Wang, one of four co-lead authors on the new paper.

“The next layer will absorb medium wavelengths and the bottom one will absorb longer wavelengths. But it’s in the top layer that we get the challenge of light-induced phase separation.”

The team used a type of perovskite material known as ABX3, which is made from a mix of different substances – including cesium, lead, tin, iodine, bromine and some small organic molecules. The top layer, in particular, is composed of mixed halide perovskites, which have a high proportion of bromine and iodine.

“What happens in light-induced phase separation of these mixed perovskites is that the bombardment of high-frequency photons causes the phases that are richer in bromine to get separated from those that are rich in iodine,” says Hao Chen, a post-doctoral researcher and co-lead author of the study.

“This leads to an increase in defects and a decrease in overall performance.”

To overcome this problem, the research team used detailed computer models to simulate the effect of altering the composition of the crystals. This work suggested two changes: removing the organic molecules for an all-inorganic perovskite structure and introducing the element rubidium.

“The introduction of rubidium suppresses the light-induced phase separation issue,” says Tong Zhu, another post-doctoral researcher and co-lead author.

“Our rubidium/cesium mixed inorganic perovskites show better light stability than [other] perovskite materials, including cesium-based inorganic perovskites and widely used organic-inorganic hybrid perovskites with similar band gaps.”

Using this knowledge, the team then designed and built a triple-junction cell with this composition. They measured its efficiency at 24.3 per cent with an open-circuit voltage of 3.21 volts. They also sent it to be independently certified by the National Renewable Energy Laboratory, which measured a quasi-steady-state efficiency of 23.3 per cent.

“In the past, triple-junction perovskite solar cells have demonstrated a maximum efficiency of around 20 per cent, so this is a big improvement. To our knowledge, this is also the first reported certification efficiency of triple-junction perovskite solar cells,” says PhD candidate Lewei Zeng, another co-lead author.

“Previous designs also tended to lose a lot of their performance in a matter of hours. By contrast, ours maintained 80 per cent of its initial efficiency even after 420 hours of operation – so that’s a big step in terms of durability as well.”

The team says that although further improvements to the performance will be needed before perovskite solar cells can compete with silicon in commercial applications, the latest study demonstrates a path forward.

“Theory tells us that perovskites have the ability to overcome a lot of the inherent limitations of silicon as a material,” Zeng says.

“But it’s not simply a matter of one displacing the other. There might be some applications better suited to perovskites, and some where silicon is better – or we could combine them both. There are a lot of exciting possibilities ahead.”

Second-hand cannabis smoke: Researchers investigate involuntary THC exposure in homes

Christopher.Sorensen — Thu, 06 Apr 2023 15:56:02 +0000

Second-hand cannabis smoke: Researchers investigate involuntary THC exposure in homes

Christopher.Sorensen Thu, 04/06/2023 - 11:56

Cutline

An air purifier can help mitigate the impact of second-hand cannabis smoke in homes, with researchers noting that THC's chemical structure makes it prone to sticking on surfaces (photo by iStock)

Safa Jinje

Topic

Breaking Research

Resarch & Innovation

Faculty of Applied Science & Engineering

�ؿ�ζSM researchers are investigating exposure to second-hand – and even third-hand – marijuana smoke in homes, including the THC that can collect on floors and surfaces.

The researchers, in Faculty of Applied Science & Engineering, have published a new study that models how THC – the main psychoactive ingredient in cannabis – behaves and transforms once it is released in an indoor environment.

The model enables researchers to explore mitigation strategies that could reduce involuntary exposure levels.

“We began our research on tetrahydrocannabinol (THC), which is the psychoactive part of cannabis that causes intoxication, because when we looked at second- and third-hand smoke, we started to see how much involuntary exposure happens,” says Amirashkan Askari, a PhD candidate in department of chemical engineering and applied chemistry.

Askari co-authored the study with U of T Engineering Associate Professor Arthur Chan and Frank Wania, a professor in the department of physical and environmental sciences at U of T Scarborough.

Between April 2021 and March 2022, Canadians spent $4 billion on regulated, adult-use cannabis, according to Statistics Canada. Dried cannabis accounted for 71.1 per cent of sales, indicating that smoking is the most popular method of consumption.

“Any type of smoking, whether it is tobacco or cannabis, leaves behind a suite of pollutants that can remain in homes,” says Chan. “We now have sufficient chemical knowledge about THC to model its behavior in a typical indoor environment.”

Moreover, involuntary THC exposure can continue long after smoking has ceased. This is due to THC’s large and complex chemical structure, which has a strong tendency to stick to surfaces and create third-hand exposure,” says Askari.

“There are a lot of surfaces indoors – tables, chairs and floors. When you calculate the ratio of surfaces to volume, it is quite elevated compared to the outdoors,” he says. “So, when a pollutant is emitted, it always has the chance to migrate from air to surfaces.

“Involuntary exposure to pollutants starts to become more important when we consider infants and children who reside in homes where this smoking takes place. Children tend to touch surfaces more than adults as they crawl or play; they are also known to frequently put their hands or objects in their mouth.”

Askari used a time-dependent indoor mass-balance model to forecast the level of human exposure to THC. The study also examined the effectiveness of mitigating strategies – from air purifiers to surface cleaners – in reducing second- and third-hand exposure from marijuana smoke.

The model was run for one simulated year under the assumption that THC from single-stream smoke (the lighted end) of a burning cannabis cigarette was emitted into the indoor air for one hour daily.

By modelling the exposure level of an adult and a toddler (who were distinguished by body weight) Askari predicted that residents of all ages who are present during smoking sessions are vulnerable to high levels of involuntary second-hand THC.

The exposure analysis also found that carpet and flooring materials were significant reservoirs of THC that migrated from air to surface. Since younger children are prone to object mouthing – a common part of infant and toddler development – this makes them especially sensitive to THC from third-hand exposure. These results, the study concludes, highlight the importance of preventing children from accessing spaces where cannabis smoking takes place, both during and after smoking.

“When it comes to improving indoor air quality, the best way to degrade air pollutants is to shut down the source,” says Askari.

“But if our aim is to suppress it, we found the most effective measures were strategies that target the air particles directly. So, if you have an air purifier unit that filters particulate matter from the air, that will reduce that exposure significantly.”

While the researchers’ initial study used computer simulation, the second phase of this cannabis and indoor air pollution research involves experiments in collaboration with the Centre for Addiction and Mental Health (CAMH).

“We had volunteers come in and either smoke or vape cannabis,” says Askari. “We measured the composition of air in real time – while they were consuming the cannabis – so we could see what happens to the air quality. We also did comparisons between smoking and vaping.”

The results from this second study have not been published, but the team hopes this research will help individuals and policymakers better understand how this source of indoor air pollution impacts the health of communities.

“We hope that people will start paying more attention to indoor air quality, not just during these high-emitting activities, but also long after they are over,” Chan says.

“Keeping our homes well-ventilated is very effective at lowering our exposures, even if it is just for a brief period of time during and after smoking.”

How U of T’s 'secret sauce' governance model set it up for five decades of success

Christopher.Sorensen — Mon, 14 Nov 2022 20:26:54 +0000

How U of T’s 'secret sauce' governance model set it up for five decades of success

Christopher.Sorensen Mon, 11/14/2022 - 15:26

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Clockwise from top left: Richard Nunn, Mary Anne Chambers, Annamarie Castrilli, Judy Goldring, Brian Lawson, Tom Simpson, Claire Kennedy, Anna Kennedy, Rose Patten, Janet Ecker, Wendy Cecil, Alice Dong and Jane Pepino (photo by Lisa Sakulensky)

Topic

Along with its partner hospitals, the �ؿ�ζSM is world renowned for its many well-publicized innovations and achievements, from insulin, stem cells and deep learning to revelations about Stalinist Russia and medieval poets.

Yet, the most important innovation in its 195-year-old history may well be one the public rarely sees: an unusual – and unusually effective – system of governance.

The university adopted a unicameral model 50 years ago in a bid to ensure business decisions supported its academic mission and vice versa. The mutually reinforcing system, known as Governing Council, has gone on to play a key role in enabling U of T to attract top scholars and researchers, as well as the necessary funding to support their work – all of which has contributed to the university’s consistently high international ranking and enviable credit rating.

U of T was the first – and, for many years, the only – Canadian university to use this model.

“I think it is fair to say that our unicameral system of governance deserves a good deal of credit for the �ؿ�ζSM’s extraordinary success,” U of T President Meric Gertler said at a recent event celebrating Governing Council’s 50^th year in operation.

U of T President Meric Gertler (photo by Polina Teif)

The final oversight body in U of T’s governance system – supported by a number of boards, councils and committees – Governing Council has the last word on literally thousands of critical decisions at the university. It comprises 50 volunteers (known as governors) representing what are often referred to as the five estates – faculty, students, staff, alumni and community members appointed by the Ontario government.

It wasn’t always this way.

Until 1972, U of T’s governance was based on a bicameral model made up of two groups. One was the Board of Governors, composed mostly of people from outside U of T who were charged with oversight of the strategic direction of the university and matters such as revenue, control of property and business and operational decisions. The other group was the Senate, which included mostly academic leaders, including deans and departmental chairs, and was responsible for the university’s academic mission, strategy, educational policy and programming.

In the early 1960s, Claude Bissell, then U of T’s president, saw a problem with this approach, calling it “double innocence.” As U of T Law University Professor Martin Friedland noted in his book, The �ؿ�ζSM: A History, “academic decisions were being made by the senate without their financial implications being known, and financial decisions were being made by the board without their academic effects known.”

Governing Council Chair Janet Ecker (photo by Polina Teif)

After almost a decade of discussion and debate (which included involvement from student leaders, including Bob Rae (a future premier of Ontario and a future governor), the model was adopted when the U of T Act was approved in 1972 by Ontario Premier William Davis. Today, current Governing Council Chair (and former Government of Ontario minister) Janet Ecker says it is an achievement to celebrate.

“We have made it to 50 years, and not only do we have rules and traditions, but we have a very strong culture of collegial governance – and we continue to build on that tradition,” she said at an anniversary event held Oct. 27.

Bringing the former two governing bodies into one “created a focal point for governance decisions,” says Jack Dimond, who was secretary of Governing Council from 1981 to 1999.

He adds that the model also places an emphasis on accountability.

“The unicameral model established a high level of transparency,” he said.

Current Secretary Sheree Drummond agrees. “The unicameral model has done what it was designed to do: bring the perspectives from all five estates into one body. With this model, anything that happens at the �ؿ�ζSM that makes its way through governance is always seen through the lens of the academic mission.

“We really do think that it is the secret sauce on being able to get our governance right.”

Drummond and her team are currently in the early planning stages of a symposium on U of T governance to be held in the spring of 2023.

U of T Chancellor Rose Patten speaks at a recent event celebrating 50 years of Governing Council (photo by Lisa Sakulensky)

Chancellor Rose Patten, an executive in the financial sector for many years, noted at the Oct. 27 event that the unicameral model continues to work well at a time when corporate and organizational accountability is receiving more scrutiny than ever before.

“In our world today, many crucial institutions are suffering a crisis of trust,” she said. “Truth and transparency are being questioned. In contrast, through our profound commitment to principles, values and inclusive excellence, the �ؿ�ζSM offers a source of credibility, confidence and hope.

“This is more relevant than ever in this time of social polarization, economic turbulence and geopolitical upheaval.”

Patten – who served on Governing Council as a lieutenant governor in council member, and was vice-chair, and then chair – praised the work commitment of governors.

“The past 50 years of governance at U of T demonstrate the impact of wise and steady leadership. It makes a difference. You make a difference, for the better.”

See a list of Governing Council’s chairs and vice-chairs throughout history

Not in the mood? Researchers examine how couples communicate when desire is low

Christopher.Sorensen — Thu, 17 Feb 2022 20:15:02 +0000

Not in the mood? Researchers examine how couples communicate when desire is low

Christopher.Sorensen Thu, 02/17/2022 - 15:15

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(Photo by Andrea Piacquadio/Pexels)

Topic

Rebecca Horne is pulling back the covers to reveal how couples communicate when it comes to sex and desire.

Rebecca Horne (photo by Drew Lesiuczok)

A PhD researcher at the �ؿ�ζSM Mississauga, Horne studies how couples resolve conflicts of interest through sacrifice – when one person gives up their own self-interest or desires for a partner – and what effect this has on the relationship. Her ongoing work is a longitudinal study of the sacrifices couples make when relocating for the sake of a partner’s job.

Yet, as Horne notes, partners also make sacrifices for each other every day, including during intimate moments.

“The domain of sex is a primary area where couples can have these conflicts, and where sacrificing might be really important – especially because it’s a sensitive and vulnerable context for a lot of people,” Horne says.

The topic is the subject of a recent study, co-authored with Horne’s colleagues at U of T Mississauga, York University and Carleton University, that was published in the Journal of Social and Personal Relationships. It looked at how romantic partners regulate expression of sexual desire, and what effect these tactics have on relationship well-being.

“Romantic partners often regulate their emotions and affection to achieve certain goals, but we wanted to know more about how partners regulate their expression of sexual desire during sex and its implications for couples’ well-being,” Horne says.

Horne notes that we might regulate our emotions to achieve goals in everyday social interactions – for example, smiling at an annoying boss for the sake of workplace harmony or job retention.

In a romantic relationship, this regulation could take the form of expressing fondness and warmth to a partner that’s not really in line with what we’re feeling in the moment, or hiding feelings of sexual disinterest from a partner or pretending to be more enthusiastic about a sexual experience than we really are.

Such tactics might be employed to smooth over the momentary blips in desire that can be caused by a bad day at work, fatigue or distraction in the moment.

“These are ways that we modify our self-interest, presumably for the benefits of our partner,” Horne says, noting that research shows this happens as much as three times per week in a typical romantic relationship.

“We may think we are interacting authentically with our partners, but we do these regulatory strategies in subtle ways.”

Yet, as Horne notes, the result is a disconnect between what we are feeling inside and what we are showing on the outside.

The study involved surveying 225 couples, most in heterosexual long-term romantic relationships, to track the link between regulation of desire and relationship satisfaction. Respondents kept individual 21-day diaries that tracked intimate relations, levels of desire and individual feelings of well-being and satisfaction.

The results showed people engaged in two kinds of primary regulatory tactics when desire was low: amplification of desire and suppression of disinterest.

Amplifying desire is about exaggeration to cover for low interest in sex. That could take the form of erotic talk, caresses or even faking an orgasm.

Suppression of disinterest, by contrast, is employed when a partner hides the fact that they’re not really interested in the experience – either in the moment or overall.

Horne says that a partner may conceal that they have lost interest during sex if they are fatigued or distracted, or if their partner isn’t attending to their sexual needs in the moment.

“When we use these strategies, we’re trying to change the way that we express emotion or desire to somebody after that emotion or desire has already been elicited,” Horne says. “These strategies can be really challenging because there’s a tension between what we’re feeling inside and what we’re showing when we’re not interested.”

Horne adds that not all sexual regulation strategies are created equal – and that sexual authenticity appears to play a key role. Those who employed these tactics reported feeling sexually inauthentic, which predicted lower satisfaction – both sexually and in the relationship.

“We found that there are drawbacks to these behaviours,” Horne says. “Our work suggests that both partners feel less satisfied with their sex lives on days when one partner amplified or exaggerated expressions of desire.”

The story is a little bit different for suppression tactics.

Those who hid their lack of desire reported feeling sexually inauthentic and detached from their own satisfaction, but it wasn’t always detrimental for their partners, who may have been convinced they were interested and engaged in the moment.

While suppressing disinterest can lead to a partner’s higher satisfaction, it can undermine one’s own feelings of satisfaction.

“These things happen during sex, and they have implications for our satisfaction,” Horne says. “When we regulate these displays, it feels sexually inauthentic.”

While all respondents reported engaging in regulation tactics occasionally, Horne says it’s important to notice if it becomes part of a pattern. Being attuned to our partners while balancing our own sexual needs can circumvent the conflicts that might lead to regulation strategies, and can amp up relationship satisfaction for both partners, Horne says.

“If things aren’t feeling right during sex, you could try to re-route, or have an open conversation about the things you like and don’t like," she advises.

“Honest and clear sexual communication is really important, and seems to have more benefits for partner satisfaction.”

The research was supported by the Social Sciences and Humanities Research Council (SHRRC) and a SSHRC Vanier Canada Graduate Scholarship.

Most Middle Eastern and North African Americans don't identify as 'white' – despite what U.S. census says: Study

Christopher.Sorensen — Thu, 17 Feb 2022 20:11:10 +0000

Most Middle Eastern and North African Americans don't identify as 'white' – despite what U.S. census says: Study

Christopher.Sorensen Thu, 02/17/2022 - 15:11

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Neda Maghbouleh's research suggests a majority of Middle Eastern and North African Americans don't identify as white, although they are recognized as such in the U.S. census (photo supplied by Neda Maghbouleh)

Topic

In the U.S. census, Middle Eastern and North African Americans (MENA) are counted as “white,” but new research co-authored by sociologist Neda Maghbouleh suggests most of them may not self-identify or be perceived that way.

Maghbouleh, an associate professor at the �ؿ�ζSM Mississauga and Canada Research Chair in Migration, Race and Identity, says categorizing MENA Americans as white obscures socioeconomic disparities that many say they face, and makes it harder to create targeted social programs and services.

“Without the numerical piece, inequities faced by this community cannot be addressed through customized resources and approaches,” says Maghbouleh, a Wall Scholar at the University of British Columbia while on leave from U of T Mississauga.

She and colleagues from UBC, Washington University in St. Louis and the University of Chicago, conducted online experiments with about 1,100 participants to see if the white label tracked with MENAs' lived experience and external perception. Their findings were published this month in Proceedings of the National Academy of Sciences of the United States of America.

The authors found that when MENA Americans aren't offered a separate classification, 80 per cent identify as white. But when they are given a MENA option, only 10 per cent exclusively tick the “white” category.

Second-generation, Muslim, non-religious and MENA Americans with Middle Eastern ancestry – and those who perceive more discrimination against MENA people – were particularly likely to opt for the MENA option. “We speculate that the MENA category may therefore represent for some a reactive ethnoracial identity, triggered acutely since the events of September 11, 2001, which led to an increase in state surveillance and public stigmatization of this group,” the paper says.

“President Donald Trump’s anti-immigrant and anti-Muslim rhetoric and policies—exemplified by the Muslim Ban, which curtailed immigration from a list of mostly MENA countries—and the significant backlash to such divisive politics may have hastened MENA peoples’ exit from the White box.”

The team surveyed 662 people who identify as MENA, asking: “What is your race or origin?” In the control group, the response options mimicked the U.S. census by listing two MENA nationalities – Lebanese and Egyptian – under the “white” category.

In the treatment group, “Middle Eastern or North African,” including Lebanese and Egyptian, was a distinct identity classification.

In the control group, 80 per cent of participants identified as white. However, 88 per cent of those in the treatment group identified as MENA, or MENA and white.

“If our goal is to have the most accurate measure of the population as possible, then we should have this separate box on the census,” Maghbouleh says.

The study also involved presenting these participants – plus 421 people who self-identified as non-Hispanic whites – with randomized profiles of fictitious individuals who varied by name, religion, language, class, skin colour and family ancestry. They were asked to classify each profile as MENA, white or Black. Their results show that whites associated medium skin with the MENA category, while MENA respondents viewed both light and medium skin colours as typical MENA traits.

Maghbouleh says a better understanding perceptions of MENA individuals can lead to more informed perspectives and better government decision-making.

“The past 40 or 50 years have been marked by a real uptick in anti-MENA discrimination – not just at the interpersonal level, but also at the level of policy and statecraft,” she says. “The power of disaggregating the MENA category in the census is that we can bring more nuance to the conversation around whiteness, and improve public dialogue about these issues.”

Improving water equity in India: Research team one of 17 to receive support from U of T's Data Sciences Institute

Christopher.Sorensen — Wed, 16 Feb 2022 20:29:17 +0000

Improving water equity in India: Research team one of 17 to receive support from U of T's Data Sciences Institute

Christopher.Sorensen Wed, 02/16/2022 - 15:29

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(Photo by Atul Loke via Getty Images)

Fanni Barocsi

Safa Jinje

Topic

Global Lens

Data Sciences Institute

Institutional Strategic Initiatives

Resarch & Innovation

Factor-Inwentash Faculty of Social Work

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Geography and Planning

A multidisciplinary team at the �ؿ�ζSM is developing tools and metrics to improve water equity in India by empowering water planners, communities and activists.

While India has made gains in expanding access to water distribution networks, rapid urbanization and inadequate infrastructure have resulted in systems that provide water for less than four hours per day in some regions, impacting 390 million people.

To cope, residents invest in water storage infrastructure and seek alternative water sources, imposing significant financial, environmental, educational, health and time costs, especially on women and girls.

“The level of complexity and inequality is staggering,” says David Meyer, an assistant professor in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering. “Since 2018, I have been exploring options for visualizing and learning from water supply schedules.”

Meyer is leading the project alongside Nidhi Subramanyam, an assistant professor in the department of geography and planning in the Faculty of Arts & Science, and Carmen Logie, an associate professor in the Factor-Inwentash Faculty of Social Work.

It is one of 17 projects receive Research Catalyst Funding Grants through U of T’s Data Sciences Institute.

With their project, “Harnessing Data to Visualize and Mitigate Urban Water Inequities within the Cauvery River Basin, India,” Meyer, Subramanyam and Logie bring together diverse disciplinary perspectives on water and data – including a deep understanding of water engineering, water governance and equity.

“Water is a cross-cutting theme that flows through so many disciplines, geographies, technologies and aspects of our lives,” says Subramanyam. “Any study about water must engage different kinds of data, expertise and knowledge systems.” 

“Professor Subramanyam has helped me realize that data cannot be interpreted properly without considering the data generation process and the data generators themselves,” adds Meyer. “Understanding the context and incentives for water utilities to report and curate data will prove key to leveraging it on an ongoing basis.” 

All projects supported by the Catalyst Grants fund multidisciplinary research teams focused on using the development of new data science methodology or the innovative use of data science to address questions of major societal importance.

“The Data Sciences Institute is committed to fostering new opportunities to cultivate multi-disciplinary collaborations between data science methodologists and researchers in various application domains,” says Timothy Chan, a professor in the Faculty of Applied Science & Engineering who is the Data Sciences Institute’s associate director of research and thematic programming. “This is just the beginning. With this inaugural round, we received 70 highly competitive proposals, which were carefully assessed by a multidisciplinary review panel.”

The Data Sciences Institute Catalyst Grants are supported by the U of T Institutional Strategic Initiatives program and external funding partners, with two of the 2022 Catalyst Grants co-funded by Medicine by Design directed to finding solutions to challenges in regenerative medicine.

See the full list of grant recipients at the Data Sciences Institute

High levels of hazardous chemicals found in Canadian nail salons: U of T study

Christopher.Sorensen — Mon, 14 Feb 2022 21:20:26 +0000

High levels of hazardous chemicals found in Canadian nail salons: U of T study

Christopher.Sorensen Mon, 02/14/2022 - 16:20

Cutline

Jackie Liang, a nail technician and community health worker at Parkdale Queen West Community Health Centre, paints nails in a Toronto salon (photo by Giovana Ramos and Praven Yoganathan)

Heidi Singer

Topic

Breaking Research

Resarch & Innovation

Dalla Lana School of Public Health

Faculty of Arts & Science

Researchers at the �ؿ�ζSM’s Dalla Lana School of Public Health, in collaboration with Parkdale Queen West Community Heath Centre and the Healthy Nail Salons Network, have found that nail technicians in discount salons are exposed to several chemicals widely used as plasticizers and flame retardants.

The study, published this week in the journal Environmental Science and Technology, found that exposure to some hazardous chemicals was higher among nail technicians than among electronic waste workers.

Miriam Diamond (photo by Camilla Pucholt)

“We were very surprised to find exposures for some chemicals up to 30 times higher among nail salon workers relative to exposures in homes, and up to 10 times higher than in e-waste handling facilities,” says Miriam Diamond, co-author and professor at the Dalla Lana School of Public Health and the department of Earth Sciences in the Faculty of Arts & Science.

The study reported higher exposures of several phthalate plasticizers, which was expected given the use of these chemicals in personal care products. One phthalate plasticizer, DEHP, which is not allowed for use in cosmetics under the Canadian Environmental Protection Act, was found at low levels.

“The finding of low exposure to the plasticizer DEHP is important – it shows the current regulations for this compound are working,” Diamond says.

However, the researchers did not expect to find high levels of flame retardants that are not known to be used in personal care products.

Several of the chemicals studied have some restrictions on their use (or restrictions are proposed) under the Canadian Environmental Protection Act. Yet, most of these chemicals are not explicitly regulated in Ontario workplaces. The specific source of these chemicals in nail salons was not determined in the study.

The chemicals in question have been associated with adverse health effects, including neurological and reproductive effects, with some evidence that in utero exposure may be important.

Victoria Arrandale

“Nail technicians have been raising concerns about the impact of their work on their bodies, including worries about reproductive, respiratory, skin and musculoskeletal health for many years now,” says Victoria Arrandale, co-author and assistant professor at the Dalla Lana School of Public Health.

Despite these concerns, nail technicians enjoy the artistry and personal care that their work entails.

“This research shows us that our federal government needs to pay attention to making the products that are used in nail salons safer for both customers and nail technicians,” says Van Tran, nail technician and nail salon outreach Worker at Parkdale Queen West Community Health Centre.

This study points to the need to consider the wide range of workplace settings when regulating chemical use in Canada. Study authors urge government and product manufacturers to make safer personal care products and safer spaces for workers and customers in the personal services sector.

“We are proud of the work we do and we would like our workplaces to be safer,” says Jackie Liang, a nail technician and community health worker at Parkdale Queen West Community Health Centre.

The study was a joint effort of researchers at U of T, Occupational Cancer Research Centre, Centre for Research Expertise in Occupational Disease and the Parkdale Queen West Community Health Centre. It was funded by the Ontario Ministry of Labour, Training and Skills Development Research Opportunity Program.

U of T art installation pulls back curtain on molecular science

Christopher.Sorensen — Mon, 20 Dec 2021 15:09:42 +0000

U of T art installation pulls back curtain on molecular science

Christopher.Sorensen Mon, 12/20/2021 - 10:09

Cutline

Ten images depicting diverse research projects pursued by investigators at U of T's Donnelly Centre for Cellular and Biomolecular Research comprise a unique art installation on campus (image courtesy of Ronit Wilk)

Jovana Drinjakovic

Topic

City & Culture

Temerty Faculty of Medicine

Resarch & Innovation

Donnelly Centre for Cellular & Biomolecular Research

Hospital for Sick Children

A remarkable collection of images normally reserved for the eyes of scientists is now available to the �ؿ�ζSM community via an exhibition celebrating cutting-edge research in biomedicine.

The recently unveiled installation, which won’t be available for general viewing until pandemic restrictions ease, features stunning data visualizations and microscopy images created by U of T researchers working in the fields of genomics, computational biology and bioengineering in the Donnelly Centre for Cellular and Biomolecular Research at the Temerty Faculty of Medicine.

Envisioned as a single art piece, the installation comprises 10 images depicting diverse research projects pursued by the centre’s investigators. These include the world’s first complete genetic network of a cell resembling a dandelion, grown-from-scratch human nerve fibers lacing the surface of a Petri dish that hold potential for regenerative medicine and the world’s first map of the human liver at the molecular level that could unlock future treatments.

With the individual pieces laser-printed on aluminum panels, which heightens image quality and preserves colour from fading, the exhibit offers visitors a chance to revel in a world less seen while they learn about ongoing research at the Donnelly Centre.

“As scientists it’s our job to make sense of data patterns and of what we capture under the microscope, and it’s easy to overlook the sheer beauty of biology,” says University Professor Brenda Andrews, who was founding director of the centre and commissioned the exhibit.

“We wanted to share this beauty with the public and to use the artwork to tell stories about some of the discoveries that have made the centre globally known as a leading hub for research in biomedicine.”

The exhibition was intended to mark the 15th anniversary of the Donnelly Centre in 2019, but its realization got delayed due to the coronavirus pandemic.

Founded in 2004, the centre brought under one roof researchers from across scientific disciplines to harness genomic technology for the advancement of science, medicine and health. During this time, the centre’s investigators carried out landmark studies that have transformed our understanding of cellular function and how it is linked to disease.

Andrews helmed the centre from its founding through three consecutive terms before stepping down in 2020 after completing her final term. Public outreach also blossomed under her leadership, with multiple initiatives aimed at instilling curiosity and the love of science among Canadians of all ages, especially schoolchildren.

For Ronit Wilk, the scientist and artist who created the piece, the exhibit is a dream come true. Wilk, who was previously a research associate in the centre and performed a lot of microscopy, always wanted to bring the “magical world” of cells to a wider audience.

“It’s a real privilege that we have as scientists to look into this world that’s invisible to most people,” said Wilk, who obtained her PhD at U of T in the lab of Professor Howard Lipshitz at the department of molecular genetics, followed by a post-doctoral stint at the Hospital for Sick Children before joining the centre in 2009.

“You transform into this tiny being looking around a cell that is colour-coded for you,” she said, referring to fluorescent markers scientists use to label different structures inside cells.

To prepare the exhibit, Wilk solicited scientific images from all 30 Donnelly Centre labs. She then selected the final 10 based on their theme, colour and composition to create a collage that captures the diverse research landscape in the centre. Wilk also artistically rendered each image using image-processing software before printing.

One panel in particular holds special value for Wilk. It shows exquisite patterns of RNA localization in fruit fly embryos, which Wilk herself took when she worked in Professor Henry Krause’s lab in the centre. The lab was the first to show that the majority of genes’ messages, transcribed into intermediate RNA molecules, show specific and dynamic localization within the embryo – and even inside individual cells – which helps ensure that the encoded proteins are made at the right place and time.

Although Wilk has moved on from the lab, she remains a staunch supporter of science by donating 10 per cent of her artist fee to foundational research.

“Basic research gets overlooked and usually there’s excitement about discoveries that can be applied right away,” said Wilk.

“But people don’t realize that by studying, for example, how RNA works, what is controlling it – those types of questions can lead to amazing discoveries later on, like we’ve seen with the first RNA-based vaccines in this pandemic.”

Researchers working on injection-free cell therapy for diabetes

Christopher.Sorensen — Fri, 17 Dec 2021 20:40:18 +0000

Researchers working on injection-free cell therapy for diabetes

Christopher.Sorensen Fri, 12/17/2021 - 15:40

Cutline

Juan Carlos Zúñiga-Pflücker and Sarah Crome are among the researchers working on generating pancreatic cells that can be transplanted to diabetes patients without being destroyed by their immune systems (photos courtesy of Medicine by Design)

Julie Crljen

Topic

Our Community

Institute of Biomedical Engineering

Insulin 100

Princess Margaret Cancer Centre

Sunnybrook Health Sciences

Temerty Faculty of Medicine

Toronto General Hospital

Resarch & Innovation

Medicine by Design

Stem Cell

University Health Network

In a person with type 1 diabetes, the body mistakenly attacks pancreatic cells that produce insulin, a hormone responsible for regulating blood sugar.

Without insulin, serious and eventually fatal symptoms will occur. Yet, imagine if, instead of needing daily insulin injections, people with diabetes could have insulin-producing cells placed back into the body, fixing the problem at its source. This is the vision of a Medicine by Design-funded research team.

The approach is not without its challenges.

“Scientists are able to generate pancreatic cells from stem cells in the lab, and they can be transplanted to someone who has lost pancreatic function, but they’ll be reattacked by the immune system,” says Juan-Carlos Zúñiga-Pflücker, senior scientist at Sunnybrook Research Institute and professor of immunology in the Temerty Faculty of Medicine. “What our work is meant to do is enable those transplants to be broadly acceptable so anyone can benefit from transplanted therapies. But the barrier of the immune system is a difficult thing to overcome, and even more so in the context of autoimmunity.”

The cells are attacked because the immune system recognizes them as harmful invaders instead of helpful therapies. It is a complex problem that demands a complex strategy – and that strategy is an emerging area of research called immunoengineering, which uses bioengineering techniques to manipulate the immune system.

The only way to currently suppress the immune system is through drug treatments, but they’re not selective; they suppress the whole immune system and leave people vulnerable to infection and illness.

The team’s strategy aims to be more precise. They want to finely tune the immune system to maintain a healthy system while not rejecting a therapeutic transplant.

Zúñiga-Pflücker says a collaborative effort is important in solving this major challenge to regenerative medicine. “We can optimize cell types and engineer effective tissues in our separate labs. But if we don’t come together to create better tools to engineer the immune system, these therapies will not be usable. It’s something very fundamental.”

The team is one of 12 sharing nearly $21 million in funding from Medicine by Design over three years. Funded by a $114-million grant from the Canada First Research Excellence Fund, Medicine by Design is a strategic research initiative that is working at the convergence of engineering, medicine and science to catalyze transformative discoveries in regenerative medicine and accelerate them toward clinical impact.

Though the research could be applied broadly across regenerative medicine therapies, type 1 diabetes makes an ideal test case, says Zúñiga-Pflücker, who is also chair of the department of immunology.

“Not only is diabetes an autoimmune disease, where the diabetic’s own immune system attacks and kills insulin producing cells, but attempts to replace the lost cells with transplanted cells are also challenged by other impacts of the disease, as well as the presence of auto-reactive immune cells,” he says. “This makes it a powerful test case for our research since we can test the transplants under multiple immune stresses.”

Zúñiga-Pflücker leads the project, which brings the work of six different labs together.

Two labs, led by the Temerty Faculty of Medicine’s Maria Cristina Nostro, a senior scientist at the University Health Network’s (UHN) McEwen Stem Cell Institute; and Sara Nunes Vasconcelos, a scientist at UHN’s Toronto General Hospital Research Institute, are using stem cells to generate tissues containing insulin-secreting cells for transplants.

Zúñiga-Pflücker says that this arm of the project is well ahead of schedule. “The Nostro and Vasconcelos labs are defining the right conditions that are necessary for generating insulin-producing cells, which are called islet cells. They’re creating newer and more effective ways to make these tissues.”

Nostro and Vasconcelos are also associate professors at U of T in the department of physiology and Institute of Biomedical Engineering, respectively.

The tissues created in their labs will be used to test the work of the other four labs involved in the project, which are concerned with engineering the immune reaction. And here, each of these labs is bringing a piece of the puzzle.

Read about research into therapeutic cell “cloaking”

Zúñiga-Pflücker and Naoto Hirano, a senior scientist at Princess Margaret Cancer Centre and a professor of immunology at U of T, work on producing regulatory T cells (Tregs). These cells can supress immune response and play a role in preventing autoimmune diseases like diabetes.

In earlier Medicine by Design-funded research, Zúñiga-Pflücker and Hirano came up with a method for producing T cells in a defined way. Some of the key breakthroughs developed as part of this research helped lay the foundation for Notch Therapeutics, a company co-founded by Zúñiga-Pflücker, which closed an $85-million (U.S.) Series A financing earlier this year.

Now, in the current research project, the two labs are crafting methods for producing Tregs and investigating how harnessing the power of other types of immune cells to work alongside the Tregs can induce the immune system to tolerate transplanted therapies.

The third investigator is Tracy McGaha, whose lab is looking at the role of macrophages, a type of white blood cell that that typically helps to attack foreign substances but can also play a role in repairing damaged tissues. McGaha is a senior scientist at Princess Margaret Cancer Centre, UHN, and a professor in the department of immunology in the Temerty Faculty of Medicine.

A fourth lab, led by Sarah Crome, is investigating a family of immune cells called innate lymphoid cells (ILCs), which act within tissues to help induce and modulate immune responses.

“We know several immune cell populations we individually study can protect from harmful immune responses and promote immune tolerance,” says Crome, who is a scientist at the Toronto General Hospital Research Institute, UHN, and an assistant professor of immunology at U of T. “The trouble is when you get into a situation that combines an autoimmune disease with rejection that can occur following islet transplantation, it’s a real challenge shutting down multiple harmful and sustained immune responses.”

Crome says that there are many different types of ILCs, so her work focuses on narrowing down which types of ILCs are best to use along with the Tregs.

Right now, each of the four labs working with immune cells are optimizing their cell types and techniques, and then, Crome says they will bring all their “best players” together.

“We’re really looking at harnessing whole networks of cells, instead of just looking at one cell population at a time. It’s bringing all of our collective expertise together into one project that makes this a powerful approach.”

Zúñiga-Pflücker says Medicine by Design has been instrumental in uniting this team of experts.

“Thanks to Medicine by Design’s support of our immunoenigneering program, we’re able to bring together multiple research sites within the �ؿ�ζSM and affiliated research institutes; UHN’s Princess Margaret Cancer Centre, Toronto General Hospital Research Institute and McEwen Stem Cell Institute; and Sunnybrook Research Institute.”

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U of T art installation pulls back curtain on molecular science

Researchers working on injection-free cell therapy for diabetes

Read about research into therapeutic cell “cloaking”