Graduate students express frustration, confusion at U of T’s advisories on lab work amid COVID-19

“Non-essential” lab research to be suspended as of March 20 due to pandemic

Graduate students express frustration, confusion at U of T’s advisories on lab work amid COVID-19

On March 13, U of T announced that it would be cancelling in-person courses for undergraduate and graduate students, but that research operations would continue. “Faculty members have a responsibility to maintain the operations of laboratory and research environments,” reads the statement

Almost immediately, confusion ensued among research staff, postdoctoral fellows, visiting scientists, and graduate students across U of T.  

Days later, on March 17, U of T officials stated that lab-based research operations must be shut down by March 20 at 5:00 pm, with the exception of time-sensitive projects under the approval of the Incident Management Team, or projects related to the COVID-19 pandemic.

But before U of T made this call, research staff and graduate students were left in limbo. 

Some researchers received directions from their respective faculties, departments, or research supervisors to remain home if possible, or work in the lab during off-peak hours. In addition, several departments advised principal investigators (PIs), or heads of research groups, to move group meetings online, prepare contingency plans for experiments, and accommodate students who feel unsafe coming into work. 

Researchers at U of T-affiliated hospitals have also received additional advisories. 

On March 16, the University Health Network (UHN) suspended “non-essential on-site research activities” until April 6. The UHN noted that projects related to COVID-19, studies essential to clinical care, and those that have “significant cost- or time-related implications” will remain active, but in-person access will be limited to “essential personnel” who have been tasked with maintaining facilities, instrumentation, or looking after animal colonies.

“We all have a pile of papers to write and data to analyze,” wrote Dr. Bradly Wouters, Executive Vice-President Science and Research at UHN, in an email to PIs at UHN on March 12. “Stay home, use the time valuably and let’s all see a bump in publication productivity over the next 6 months.”

The Varsity contacted graduate students across various science departments at U of T to determine how their departments, labs, and supervisors are responding to COVID-19. 

Mixed signals: graduate students received little direction from departments, PIs

Lee*, a public health graduate student, said that their PI initially expected their team to come into the lab every day amid cancellation announcements, even though Lee’s lab does not require wet-lab or on-site experiments.  

“My PI has given us no direction on whether we’re to come in but it seems like the expectation is yes,” wrote Lee to The Varsity. Lee noted that they felt their PI’s message to lab members “seemed to downplay the situation.” 

Similarly, Alex*, a biology graduate student, wrote to The Varsity that while their PI encouraged lab members to take precautions, like washing their hands often, they still expected students to work in the lab. 

“[They want] us to do more work just in case we won’t be able to in the future. For example if we become sick and need to self-isolate,” Alex wrote. “[They think] there’s less distractions now since we don’t have as much TA work.”

“I am concerned about getting infected but since it’s worse in older people I’m more concerned about getting infected and then infecting others,” Alex noted. 

Following U of T’s announcement on March 17, both Lee and Alex’s PIs responded by either telling them to stay home, or to make preparations to work from home. 

In a comment to The Varsity, the University of Toronto Graduate Students Union (UTGSU) wrote that they have been communicating with administration regarding lab closures.

“The UTGSU Executives are disappointed that it took so long for the University to take this step, but remain advocates for safe working conditions for our members.”

Prioritizing health and safety: “It’s been instilled in the lab culture”

While some graduate students felt frustrated at a lack of response from their supervisors, several graduate students told The Varsity that their PIs have taken extra steps to support their lab members during the pandemic. 

Chemistry PhD candidate JoAnn Chen wrote to The Varsity that her PI had not explicitly said anything about COVID-19, but her lab’s culture has always made it possible for students to stay home when they are feeling sick.

“In my lab, the students have decided [that] we’ll come in when we have scheduled instrument time, but otherwise, we won’t be coming to lab,” Chen wrote on March 13. “Our supervisor has always been accommodating in terms of sick days and vacation, so we were able to decide as a group, but in other labs, the PI probably needs to say something.”

After U of T’s shutdown notice for non-essential lab work on March 17, Chen’s PI informed lab members of plans to shut down instruments. 

Molly Sung, also a chemistry PhD candidate, is scheduled to defend her thesis on April 7. “I have my PhD defense coming up – the next group meeting was supposed to be my practice,” wrote Sung to The Varsity on March 15. Her PI, Professor Robert Morris, offered to meet with her one-on-one to practice her talk. 

On March 17, Sung found out that her defence will take place over a video call, but the public portion of her defence has been cancelled.

Graduate students worried about research setbacks

Even though classes and meetings shifted online this week, Kyle*, a graduate student in biology, expressed guilt about their inability to complete lab work. “It’s hard to sit at home when you know you have a growing pile of work that has to be done at the lab,” Kyle wrote to The Varsity. “This will either set you behind or create more work to do.”

Similarly, Ash*, a neuroscience graduate student who works with mice, wrote that they were worried about how a lab shutdown would impact their mouse colonies and degree progress. “I have a lot of big ideas but no concrete evidence to link everything together yet,” Ash wrote. “If research is shut down, it’s not easy to get back.”

Ash said that their PI is looking into “whether the research animals have to undergo mass euthanasia.”

“It is a huge waste of research funds if it happens and we’d like to prevent it as much as possible,” Ash wrote.

Avery*, a pharmaceutical sciences graduate student shared this sentiment. “I’m definitely worried about the impact this will have on my research.”

“The guilt I feel at the possibility of missing a few weeks in [the] lab is immense. But the guilt I feel about not doing my part to stop the spread of COVID-19 is also huge.”

*Names have been changed for privacy.

The Varsity has reached out to U of T and the UHN for comment.

The promise of the human microbiome in cancer research

Trillions of microbes in the human body could play a crucial role in cancer detection and treatment

The promise of the human microbiome in cancer research

Trillions of microorganisms are scattered throughout the human body, outnumbering human cells by a ratio of 10 to one. These living creatures have become an emerging target for cancer treatment.

In a recent U of T-affiliated review, scientists from the Princess Margaret Cancer Centre and the University Health Network have explored research on the complex relationship between the human microbiome and cancer. 

What is the human microbiome?

The human microbiome is the collection of genomes present in the microbes that live on or in humans. These microbes include not only bacteria, but also fungi, viruses, and prokaryotes, wrote Dr. Brian Coburn, a co-author of the study and a professor at U of T’s Department of Laboratory Medicine & Pathobiology.

Most microbes are concentrated in the genital tract and mucosal surfaces, which are the membranes that cover internal organs and various body cavities. A human’s microbiome develops from birth and is influenced by the mother’s microbiota, as well as individual genetic makeup and environmental exposure. 

The microbiome has been suggested to be directly causing cancer through inflammation of mucosal surfaces, systemic impairment of metabolism and the immune system, and influencing the effectiveness of anti-cancer therapy.

Certain bacterial species have been identified as more abundant in patients that respond to certain types of anti-cancer therapies than others, explained Coburn.

Researchers have also found that many tissues have their own distinct bacterial, viral, and fungal populations. Cancerous tissue itself appears to have an altered microbiome. Further evidence shows differences in the microbial composition of specific cancers. For example, scientists have found distinct microbial composition patterns in subtypes of breast cancer.  

How the microbiome could be a target for anti-cancer therapies

Positive responses to anti-cancer therapy are typically “defined by a reduction in the size of their tumor of 30% or more,” wrote co-author Dr. Aaron Hansen, an oncologist at the Princess Margaret Cancer Centre, to The Varsity. “This is a desirable outcome for treatment. Patients who do not respond to therapy typically have a growth of the tumor by 20% or they develop new metastasis.”

Metastasis is the growth of cancer at a secondary site, away from the initial location of cancer. 

Emerging evidence has also described tumour activity as closely related to abnormal microbiota in adjacent tissues. Scientists have suggested that microbiota may cause inflammation ⁠— or altered inflammatory signaling ⁠— in these tissues, which could promote the growth and spread of tumors. However, more research on tissue samples from cancerous and non-cancerous patients is needed to validate the results.

Scientists are looking at ways to manipulate the microbiome in humans, and often use animal subjects to test their hypothesis. These continue to be an important but imperfect tool for testing research hypotheses for human diseases.

“There is some evidence from observational studies and animal models that the gut microbiota is associated with response to some cancer therapies,” wrote Coburn, “but causality [sic] in humans is a difficult thing to definitively prove and this remains an untested hypothesis.”

Probiotics have been considered as a form of additional treatment for approved cancer therapies. In research involving mice, scientists have shown that probiotic supplementation could decrease the number of tumour cells and their proliferation.

Other researchers have found that the introduction of the bacteria Lactobacillus to mice decreased tumour size and improved survival rates, suggesting that altering the microbiome may have an impact on suppressing tumour growth.

The lasting challenge of research in this field

Research in this field has proven challenging because individuals vary in their responses to antibiotics, probiotics, and other interventions that affect the microbiome. There is a wide range of different types of probiotics, noted Coburn, and they can have vastly different effects on different patients, or they can have no effect at all.

“We don’t know what to use, how much, when or for how long and in which patients – it remains a very large research challenge [that] will take decades to thoroughly investigate,” he explained.

Furthermore, animal models “will always be limited in how they are applied to human disease and treatment,” he wrote. “In the end, only human studies (especially randomized controlled trials) can prove or disprove that a new type of therapy is safe or effective.”

Research on the effect of the microbiome on cancer is relatively new. Well-designed, controlled, and structured observational and interventional studies would shed light on this growing field. Such studies would enable clinicians to assess the link between the microbiome and cancer, as well as the microbiome’s potential in cancer diagnosis and treatment.

New research, wrote Coburn, could help clinicians “determine if the relationship is causal or simply coincidence and whether [the microbiome] is a useful therapeutic target.”

Weeding down the environmental cost of cannabis cultivation

How yeast could revolutionize an unsustainable industry

Weeding down the environmental cost of cannabis cultivation

Canada has the world’s largest market for recreational cannabis. Its legalization last year lit the path to a ‘higher,’ more liberal future, and was a bold move that came at an opportune time for science.

Cannabis-related research and education are flourishing in this political landscape — the demand for cannabis expertise is going through the roof, creating a space that begs for attention from researchers.

But cultivating cannabis for both research and recreation comes at a cost: it is both expensive to produce at industrial scales and damaging to our environment.

With the many trailblazing studies on cannabis underway, an especially creative finding detailing a new cultivation technique was published in February as a letter in Nature. Dr. Jay Keasling’s lab at UC Berkeley engineered yeast to produce pure cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD). This discovery motivates a reconsideration of current cannabis production policies and strategies.

The ecological and economic costs of cultivating cannabis

A recent CTV News article titled “Canada’s largest outdoor cannabis farm ready for growth” reports that prior to the farm’s opening, most legal cannabis had been cultivated in indoor facilities.

This should be a cause for concern. The financial cost of these methods of production is superseded only by the environmental costs. The cultivation of cannabis is not only water- and nutrient-intensive, but also usually requires land clearing, causes agrochemical pollution, and erodes soil. The unenlightened idea of an outdoor farm could cause severe ecological harm and environmental degradation. 

The production of one kilogram of processed cannabis releases 4600 kg of carbon dioxide emissions into the atmosphere. That is the amount of carbon dioxide produced by 3 million cars in the US.

An indoor facility is an even worse prospect. A 2012 study published by Dr. Evan Mills in Energy Policy, analyzed a four by four by eight-foot module of indoor cultivation. The results show that it would require 13,000 kilowatt-hours per year for utilities such as high-intensity lighting, ventilation, pre-heating the irrigation water, space heating, and air conditioning within the indoor facility. At this rate, Mills estimated the financial cost of growing cannabis from electricity alone to be $6 billion per year in the US.

The environmental costs are even more astounding — fossil fuels have caused carbon dioxide levels to be raised four times the atmospheric usual. At this rate, Mills estimated that the production of one kilogram of processed cannabis releases 4600 kg of carbon dioxide emissions into the atmosphere. That is the amount of carbon dioxide produced by 3 million cars in the US. The ecological horror entailed would cause both Greta Thunberg and anyone who understands climate change to have nightmares.

A sustainable alternative to indoor and outdoor cultivation of cannabis

The environmental burden of producing cannabis is too costly using the current methods of cultivation. It would be a great mistake on the industry’s part not to consider alternatives. One beneficial method that could help solve these problems is the procedure co-outlined by Keasling.

The new method is said to cover the deficits of current cannabis production methods. The researchers created an experimental setup that would be cost-efficient, environmentally safer, and enable direct synthesis of THC and CBD.

By developing a fermentation process using brewer’s yeast, the scientists have engineered a way to produce cannabinoids from a sugar called galactose. The process could help rein in the carbon footprint and financial cost of cannabis cultivation, as well as enable efficient production of specific cannabinoids normally found in trace amounts of plant-cultivated cannabis. 

It could be a great breakthrough for Canadian researchers studying cannabis to investigate the application of this new method, along with companies that sell products imbued with THC and CBD, such as cannabis-derived oils.

Sustainably cultivating cannabis can have medical applications

By developing a fermentation process using brewer’s yeast, the scientists have engineered a way to produce cannabinoids from a sugar called galactose.

The efficient synthesis of THC and CBD through the sustainable yeast-based method could be especially relevant in medicine due to the effects of the isolated compounds on patients.

According to a research review on effects of THC on cognition, the compound can reduce activity in major parts of the brain, including the prefrontal cortex. THC is thus generally linked to impairment of cognitive abilities, as well as psychotic symptoms and anxiety. On the other hand, CBD, which is an antagonist of the cannabinoid receptor, increases activation of other major parts of the brain, such as the prefrontal cortex and striatum.

The review further concludes that CBD reduces anxiety, thus opposing the effects of THC. When subjects are given a combination of equal amounts of THC and CBD, in comparison to pure THC, it was observed that CBD subdued the detrimental effects caused by THC. The risks associated with CBD products are therefore thought not to be associated with CBD itself, but other cannabinoids that can be found in the product.

Controlling the THC:CBD ratio in potential medications derived from cannabis could hold promise in medical research. Dr. Lakshmi Kotra, a senior scientist at the U of T-affiliated Krembil Research Institute, illustrated the example case of Sativex in an interview with The Varsity.

Sativex is a Canadian drug that has a 50:50 ratio of THC and CBD and is usually given to patients with multiple sclerosis. There is anecdotal evidence that suggests that smoking cannabis has better effects than Sativex.

Another example demonstrating the importance of controlling for specific ratios of THC and CBD stems from research on potential treatments for schizophrenia. The effects of potential cannabis-derived treatments have been shown to vary based on the THC:CBD ratio, highlighting the importance of its control.

While scientists can extract pure cannabinoids from cannabis plants, it’s an expensive and arguably arduous method that produces low yields. New approaches such as the yeast-based methods could offer more efficient ways of producing these medically relevant compounds.

The wider impact of sustainable cultivation

It may be a great breakthrough for Canadian cannabis-based companies to investigate such innovative, ecologically safe, and cost-effective methods, and would also allow the nation to set an example for the world with progressive legislation. It would be a great showcase of sustainable development and economics — a perfect way to lay down roots for a new industry that is bound to thrive in the coming years.

We are creating history with respect to cannabis legislation and distribution. With the nation-wide legalization of cannabis, along with Germany and New Zealand importing Canadian-grown cannabis, it becomes imperative to pay attention to current methods of growth, the sustainability of which should be equally considered for its ecological and financial costs.

Insulin may ward off infections

University Health Network researchers find insulin could play a role in the immune system

Insulin may ward off infections

It was Frederick Banting’s co-discovery of how to extract insulin in the early 1920s at U of T that continues to save millions of lives across the globe, providing hope to patients suffering from diabetes who, in previous years, had none.

For Dr. Sue Tsai and Dr. Dan Winer at the University Health Network (UHN), insulin is the gift that keeps on giving.

“In [our] field a lot of people are looking at how obesity causes inflammation,” said Tsai. “But no one really knows it affects the immune system when it comes to infectious diseases, or cancer, because so many things are altered [and] your hormones are all dysregulated.”

Insulin’s role in diabetes is well-researched, but little is known about the role it has in regulating T cell function and what leads T cells to stop responding to insulin.

Tsai wanted to determine what factors cause obese individuals to have a reduced response to vaccinations, develop more infections, and be more likely to develop cancer.

They narrowed their target to insulin, because individuals become resistant to it when they become obese.

Tsai, a postdoctoral fellow at UHN, and Winer, an Assistant Professor in U of T’s Department of Laboratory Medicine and Pathology, have uncovered an insulin signalling pathway that elicits a response from infection-fighting T cells when they are activated.

Insulin, a pancreatic hormone, promotes glucose uptake via downstream signalling pathways. These pathways involve the binding of the insulin hormone to an insulin receptor (INSR).

Immune cells, such as B cells and T cells, that protect the body against infection also possess this receptor. Tsai and Winer hypothesized that the binding of this receptor would stimulate T cell activation and proliferation, leading to a strong and immediate immune response.

In their study, Tsai and her colleagues compared T cell function in mice without the INSR to those with the receptor.

“We found that T cells [without INSR] become less functional, and when we give the mice influenza [H1N1], they do worse,” explained Tsai. “They lose more weight and then they have a weaker immune response against the influenza.”

INSR played an integral role in maximizing the potential function of the T cells in mice by increasing their nutrient uptake and in turn generating energy through ATP production during inflammation and infection.

The researchers’ findings provide some reasoning as to why vaccines in obese individuals may not be as effective. Many obese individuals are insulin-resistant and, as shown in this study, could therefore have a weaker T cell response.

T cells are integral to the efficacy of a vaccine, as they recruit infection-fighting antibodies and aid in immunological memory.

Tsai hopes to continue exploring the link between insulin and immunity, and is currently investigating insulin signalling in B cells. She believes the findings of these studies could have wide-ranging applications.

“The most obvious thing is influenza vaccines. How can we develop a vaccine, and what additional signals can we add to the vaccine to get them to work better in individuals who are insulin resistant?” said Tsai.

“Also, tumour immunotherapies. Do obese people respond to these therapies differently than non-obese people and does insulin resistance play a role in that?”

In the future, the insulin signaling pathway could also be used to study and find ways to ‘boost’ the immune system and develop vaccines that would work more effectively in obese individuals.

Tsai’s findings were published in Cell Metabolism last month, almost a century after the discovery of insulin.