Retirement celebration features fond recollections
CSB held an emotional get-together on Oct 18th in the Faculty Club to celebrate the retirements of Professors Dorotea Godt and Rudi Winklbauer, and of our Chief Adminstrative Officer Tamar Mamourian.
Chair Nick Provart noted that Prof Godt and Prof Winklbauer are valued experts in flies and frogs respectively, with Prof Godt focusing on development of the egg chamber in Drosophila and Prof Winklbauer centred on cell movement during gastrulation in Xenopus.
These distinguished developmental scientists were recruited from Germany to UofT’s Department of Zoology and participated in its restructuring into Cell & Systems Biology.
Professor Tony Harris shared his gratitude for their contributions as colleagues and as mentors to him as a developmental biologist. He noted how each of their publications, whether research or analysis, advanced and strengthened the field.
Prof Godt mentioned how grateful she was to be able to rely on staff and students for the smooth running of her labs and courses. Former students noted how Prof Winklbauer’s deep kindness helped them through difficult times.
In speaking about Tamar’s retirement from CSB, former Departmental Chairs John Coleman and Daphne Goring praised her abilities, whether it was the insight of knowing how to correctly (legally) sequester funds, or of who to contact for repairs. “When Tamar had a question, she wouldn’t stop until she found the correct answer.”
CSB is grateful to Professors Godt and Winklbauer and to Tamar for their contributions and look forward to their future advice and visits to Departmental functions.
Mitchell Lab finds cancer enhancer in the genome that drives tumour cell growth
Researchers in the Mitchell lab have found that cancer cells can hijack DNA normally used when tissues and organs are formed to enhance tumour growth. The pathway they found is active in multiple cancer tissues, showing that this mechanism is relevant for many types of cancers.
The human genome is amazingly complex, containing both genes and instructions to turn genes on and off in different contexts. “The genome is like a recipe book written in DNA that gives instructions on making all the parts of the body.” explains co-author Dr. Luís Abatti. “In each organ, only the recipes relevant to that organ should be open, whether it’s lung or breast or some other tissue.
We found some cancer cells were opening the wrong pages in their book, one that contains the SOX2 gene, which is normally needed in many types of stem cells but can also cause tumours to grow in an uncontrolled way.”
The UofT researchers analyzed genome data to look for an ‘enhancer’ region that could activate SOX2 in stem cells and in cancer cells. The enhancer they found could activate SOX2 but it was not open in stem cells.
Instead, they found that the enhancer was open in many different types of patient tumours meaning this could be a “cancer enhancer” active in bladder, uterus, breast and lung tumours. Unlike many cancer-causing changes, this mechanism does not arise out of mutation due to DNA damage but instead is caused by this part of the genome becoming more open when it should be staying closed.
The researchers wondered if cancer cells had increased growth due to this enhancer. When they removed the enhancer in lab-grown cells, the cancer cells were defective at creating new tumour colonies.
“Having figured this out, an important question remained: why our cells would have this region of DNA that makes cancer worse?” asserts co-author Prof. Jennifer Mitchell. “We found that removing this region from the genome of mice caused an airway defect; these mice do not form a separate passage for air and food in their throat as they develop”.
So this potentially dangerous “cancer enhancer” region is likely in our genomes to regulate this same process during human development. However, if a developing cancer cell opens up this region, it will form a tumour that grows more quickly and is more dangerous for the patient.
“Now that we know how the SOX2 gene gets turned on in these types of cancers we can look at why this is happening. To use Luís’ analogy, how did the cancer cells end up on the wrong page of the recipe book? Something really interesting that we found is that two proteins that were known to have a role in the developing airways (FOXA1 and NFIB) are now regulating SOX2 in breast cancer.”
The enhancer is activated by the FOXA1 protein and suppressed by the NFIB protein. That means that drugs suppressing FOXA1 or activating NFIB may lead to improved treatments for bladder, uterus, breast and lung cancer where the enhancer is open.
This research is published as a Breakthrough Article in Nucleic Acids Research as “Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma”
Congratulations 2023 Barrett Award winners!
Students in CSB397, 497, 498, 499 and the Research Opportunities Program presented posters describing their research at the 2023 CSB Undergraduate poster session on Wednesday, September 6, 2023. Four of these students earned the F Michael Barrett Award for their excellent presentations.
Yolanda Liu presented research from her CSB397 Research Abroad project in Singapore on "Evaluating the pathogenicity of a rare TNNI2 variant in a family with recurring fetal akinesia".
Welna He described her results in the Calarco lab on "Functional characterization of RNA-binding proteins and their genetic interactions in the C. elegans PVD neurons".
Damo Shi presented their results from the Harris lab on "Confinement by Nearby Tissues Mediates Amnioserosa Cell Alignment during Drosophila Embryo Development".
Vicky Zhi showed the work she did in the Mitchell lab on "Linear Chromatin Proximity Regulates Enhancer-Mediated Expression of Lefty Genes in Mouse Embryonic Stem Cells".
Research abroad by Liu was assisted by the Centre for International Experience. Research by He and Zhi was facilitated by earning prestigious NSERC Undergraduate Student Research Awards, and Shi's studies were supported by the coveted University of Toronto Excellence Award.
Thank you to Genna Zunde for all of her hard work in organizing this event. Thank you to Elly Chen, Anna Kozelj and Lisa Matchett for helping with this poster session. Thank you to all the presenters and congratulations to the winners!
New appointments show that CSB is building and broadening
CSB is building on excellence and broadening our research thanks to two recent appointment by the University of Toronto.
Congratulations, Professor Plotnikov!
On July 1st, our colleague Sergey Plotnikov received tenure and a promotion to Associate Professor.
Plotnikov is a world leading researcher, with recent publications in Nature Physics and Developmental Cell.
Plotnikov's lab is interested in understanding the mechanisms used by mammalian cells to sense and transduce physical inputs from the microenvironment. Plotnikov is particularly curious about by the way these mechanical cues guide cell migration.
Welcome Professor Shafer!
We also welcome a new colleague, Maxwell Shafer, who is appointed as an Assistant Professor in Cell & Systems Biology as of July 1st.
Professor Shafer will decode the genomic and cellular mechanisms of sleep evolution using comparative approaches across vertebrate species, including functional genomics, bioinformatics, cell & molecular biology, neurobiology, and evolution.
Melody Neumann's Excellence in Education recognized with a Full Professorship
Congratulations to Melody Neumann, who has been promoted to the rank of Full Professor, Teaching Stream in Cell & Systems Biology!
Neumann is Director of the Human Biology Program, where she invites students to be active participants in the interdisciplinary study of human biology.
Neumann is a world leader in science education. Her research focuses on many aspects of undergraduate teaching, including the development of innovative and evidence-based practices.
Neumann's excellence is recognized through the President's Teaching Award from UofT, the European Conference on eLearning Excellence Award, the Society for Teaching and Learning in Higher Education D2L Innovation Award. She is also an Online Learning Academy Advisor in UofT's Faculty of Arts and Science.
Congratulations, Professor Melody Neumann!
End of the tunnel for crop loss due to parasitic plants
Parasitic plants devastate entire fields of crops every year, resulting in billions of dollars of food lost. As food prices rise, protecting crops from parasitic plants is crucial to keeping meals affordable. Researchers at the University of Toronto have discovered a path to rescuing crops by finding an unexpected feature of the protein that leads parasitic seeds to sprout.
Healthy plants secrete a hormone called strigolactone. Hormone receptors in seeds of the parasitic Striga plant respond to this sign of abundance by activating the Striga seed to sprout. The parasitic seedling then infiltrates the roots of a healthy crop plant to steal its nutrients.
The shape of a receptor protein can change as it is activated, and knowing this shape helps design chemicals to block the receptor. All previous attempts to capture strigolactone bound to its receptor were unsuccessful.
Amir Arellano Saab in Prof Peter McCourt’s lab identified a number of receptor mutants that he predicted would capture the hormone. He worked with Dr Peter Stogios of BioZone to crystalize these purified proteins bound to hormone.
Arellano Saab and Stogios were excited to obtain crystals of high-affinity HTL5 receptor bound to strigolactone. They applied structural biology techniques and AI-powered molecular dynamics simulations to resolve the shapes inside the crystal.
As Stogios presented the result at lab meeting, his colleagues gasped in astonishment. They could clearly see a tunnel through the protein which wasn’t there if there was no hormone. The most likely role for this tunnel is to dispose of the hormone once it is processed.
Scientists will now be able to design chemicals to block the tunnel, preventing the sprout-promoting activity of the receptor. Striga is a frequent cause of crop loss in Africa, so this will greatly improve yields for African farmers in particular.
These results are published in the journal Nature Plants as “Structural analysis of a hormone-bound Striga strigolactone receptor”.
Staying up for the Awards: Anita Taksokhan earns CSS-Jazz award for sleep research
A good night’s sleep leads to an active, productive day for most of us, but a rare condition called idiopathic hypersomnia (IH) can lead some people to struggle to stay awake even after a good night’s sleep.
CSB graduate student Anita Taksokhan has earned a grant supported by Jazz Pharmaceuticals to probe the neurological roots of this rare condition in Prof John Peever’s lab.
Taksokhan earned her award through a competitive pitch presentation at the annual Canadian Sleep Society meeting. Taksokhan’s presentation was judged by a panel of sleep researchers to be the most captivating proposal. She did so well that the audience awarded her presentation an additional people’s choice award!
Her CSS-Jazz proposal builds on studies in Japan that have identified a single genetic change that is linked to IH. This change alters the orexin protein. Lack of orexin has been linked to other sleep disorders, including narcolepsy.
Taksokhan will use CRISPR-Cas9 gene editing in mice to reproduce the small change in orexin seen in the Japanese study. She will then assess these mice for symptoms of idiopathic hypersomnia. Women are more often affected by IH, so an important feature of Taksokhan’s proposal is the use of female mice.
Taksokhan is grateful for this independent funding to support her PhD research. It is an impressive accomplishment for a graduate student to secure their own funding. Congratulations, Anita!
High school students explore research in biology as a career at CSB
Professor Ritu Sarpal organized a two-day Biology workshop, on Apr 15 and Apr 29, for Black high school students enrolled in the Pursue STEM program in her role as Professor and as a member of CSB EDI committee.
Pursue STEM supports Black high school students interested in STEM fields, and is delivered in partnership with Leadership by Design (LBD), the University of Toronto Office of Student Recruitment, and other Departments within our Faculty of Arts and Sciences.
The workshops were designed to give students a flavor for ongoing cutting-edge research in Biology.
Two-headed flatworms
Professor Sarpal gave a talk on stem-cell mediated regeneration and how planarian flatworms serve as a great model system for studying this process.
For their laboratory work, students used wild type flatworms and experimental flatworms in which a gene called β-catenin was turned down using the dsRNA approach. Students cut their worms on the first day, and then examined the regenerated worms on their second visit two weeks later.
They were extremely excited to see that a piece of the wildtype worm missing both a head and a tail was able to regrow a completely new head and tail in just two weeks.
An even more exciting result for the students was to find that a similar piece obtained from worms lacking β-catenin grew two new heads instead of a head and a tail, highlighting the role of this gene in controlling regeneration.
Hungry roundworms
In a workshop led by Professor John Calarco and PhD student Kailynn MacGillivray (Saltzman lab), students learned about a tiny roundworm called C. elegans. This model organism, affectionately known as ‘the Worm', is widely used in Biology due to its versatility in genetic studies.
Calarco presented a short seminar highlighting the features of C. elegans. The students then acted as geneticists, observing different strains of normal and ‘mutant’ worms and taking notes on their appearance and behaviour.
In a second module, students were asked to time and ‘track’ normal and mutant worm behaviour as these animals foraged towards a food source.
At the end of the workshop, MacGillivray and Calarco held a Q and A session to address any questions from the students about undergraduate and graduate studies in the life sciences at UofT, as well as other questions surrounding career decisions.
When asked to comment about their workshop experience, students wrote:
- “Enjoyable! It made me want to learn more about the regenerative properties of different species and how it can be applied in medicine.”
- “I enjoyed the workshop, it was fun learning about regeneration and questioning if other animals regenerate too. It was my first lab experience and it made me want to have more.”
- “I was not a fan of Biology as I believed it to be less useful than the other two sciences. However, with this workshop I was able to see how broad biology is in terms of species, treatments, experiments and molecular functions. I now want to see how regeneration plays a role in humans especially the eye.”
“It was great to see that such workshops can create a lot of enthusiasm for biology among the high school students,” said Professor Sarpal. “I’d like to thank our graduate students Rebecca Tam and Kailynn MacGillivray, and teaching lab staff Lisa Matchett, Reta Aram, and Pui Tam, for their invaluable assistance with the workshops.”
Keep on moving: paralysis of narcolepsy relieved by chemogenetic cell therapy in mice
Anyone affected by the sleep disorder narcolepsy can experience sudden paralysis that causes them to collapse in the middle of their day, a symptom called cataplexy. Drug treatments for cataplexy are available but must be taken in two doses, one at bedtime and the other in the middle of the night, disrupting sleep. Researchers at the University of Toronto have shown promising results in mice for treating cataplexy with therapeutic cells.
Dr Sara Pintwala of the Peever laboratory in Cell & Systems Biology focused her studies of cataplexy on the neurotransmitter orexin. The daytime sleepiness and cataplexy of narcolepsy occur when orexin neurons in the lateral hypothalamus of the brain either degenerate or fail to produce orexin.
Pintwala collaborated with the Belsham laboratory in the Department of Physiology to grow orexin-expressing neurons in the lab. She engineered these cells so that they were activated to express orexin by a specific chemical, a technique known as chemogenetics. This allowed her to tune the levels of orexin produced by the cell prior to transplantation, reducing the number of mice needed for the experiment.
Cataplexy occurs more often when the affected individuals experience positive stimuli. Pintwala was able to increase observed cataplexy episodes by keeping mice in a social environment with exercise wheels and by including chocolate with their food. She could then test the ability of her treatments to relieve cataplexy in this environment.
Stable patterns of behaviour like sleep and wakefulness are coordinated in the lateral hypothalamus of the brain. Pintwala was demoralized to find that transplanting her engineered orexin-expressing cells into this region failed to restore normal patterns of behaviour in mice lacking orexin. However, she knew that the neural circuits that promote wakefulness and motor behaviours form connections to a separate brain region called the dorsal raphe.
Pintwala felt guarded optimism when she observed that transplanting orexin-expressing cells directly into the dorsal raphe reduced both the number of cataplexy episodes and the severity of cataplexy. Further experiments confirmed relief from the symptoms of cataplexy. Pintwala was certain of her success when she observed that the treated brains showed hundreds of orexin-expressing neurons enervating the dorsal raphe.
Pintwala and Peever’s research, published in Current Biology as “Immortal orexin cell transplants restore motor-arousal synchrony during cataplexy” provides evidence towards the use of cell replacement therapy as a therapeutic strategy for narcolepsy.
The next step in this process will be alleviating the sleepiness experienced by those affected by narcolepsy. This means future experiments will focus on the sleep circuits that impact a region called the locus coereleus as a target for treatment.
Science Rendezvous was a huge success for CSB!
On Saturday, May 13th, St George Street was shut down in front of the Ramsay Wright Building for Science Rendezvous 2023. CSB was out in force to share research activities in Animals, Plants and Bacteria designed by CSB graduate students, staff and Professors.
Over four hundred people stayed to engage with us out of the thousands who passed by to take a look. “Several families were translating from English to their mother tongue for their young kids, which was a great mirror of Toronto's diversity,” noted CSB grad student Tatiana Ruiz-Bedoya.
Visitors loved the regenerating flatworms that Professor Ritu Sarpal and Leo Xu showed. Their demonstration showed how gene alterations could make decapitated worms regrow two heads. One young visitor commented "I wish I could have two heads like the mutant flatworms. I would then have two brains and I would be supersmart!"
The movement of tissues during embryo Development was demonstrated by Sirma User with the aid of colourful plaster models and online tools. “A few people (even some kids) wondered about what happens if we take a group of cells and try to grow them outside the embryo,” User recalls, “This is the kind of insightful question we expect from our upper year students and led to some detailed discussions.”
Developmental Biology was further exemplified through the “Glowing Flies” activity created by Gordana Scepanovic and Veronica Castle. Using a fluorescence microscope, visitors could see glowing GFP-tagged fly embryos. They also looked at living flies in glass vials: “Kids definitely loved making the flies with the temperature sensitive Shibire mutant pass out by warming them up with their hands!”, observed Scepanovic.
Our research in Neuroscience was represented by Dr Melissa Seranilla and Haushe Suganathan, who attached electrodes to visitors to show them the signal travelling from their brain to the muscles of the arm.
Dr Neil Macpherson presented artwork created for the department, including cell biology images, and paintings and jewelry inspired by research in gene expression.
Stem Cell Biology was explored by Tiegh Taylor and Nawrah Khader. They designed a marble run with marbles representing tissues developing from stem cells. Changing the flow of marbles with pegs or barriers representing certain proteins caused the marbles to gather in a bin representing specific organs. “We showed visitors that that our bodies are amazing at using stem cells during development to create complex organs” says Taylor. ”We told them that the better we understand that process, the closer we are to being able to regrow organs in a lab.”
Dr Zoe Gillespie and Shanelle Mullany showed how DNA is extracted by having visitors mush up banana in a plastic bag and making the banana DNA crystallize in the bag. This led to discussions of the importance of DNA for research in Genomics and Computational Biology.
Professor Heather McFarlane created a poster on Plant Biology detailing how cell walls protect, support and hydrate plants. The poster contained activities visitors could use at home to see cell walls in celery. Kathryn McTavish and Tatiana Ruiz-Bedoya displayed some fascinating plant specimens from our teaching collection, and discussed their research in plant immunity by showing the effects of bacterial infection in plants.
Imaging specialist Dr Kenana Al Kakouni showed microscope slides of animals, plants and bacteria to reveal the diversity of Cell Biology, and provided stickers of striking cell images. Visitors were impressed by the degree of magnification our microscopes displayed.
Using plastic models and diagrams, Natalia Gajewska and Sofia Karter encouraged our younger visitors to make organelles out of modelling dough, fuzzy balls and pipe-cleaners. They explained the role of individual organelles, such as chloroplasts using sunlight to make sugar, and mitochondria breaking down sugar to make ATP to fuel the cell. As small hands busily worked, Gajewski and Karter used follow-up questions from kids and parents to discuss Departmental research.
Thank you to our presenters for their amazing work designing exhibits, engaging with our visitors and getting them excited about Cell & Systems Biology!! We are also grateful for the hard prep work done in advance by Samuel Delage, Fernando Valencia, Lisa Matchett, Anna Koselj, Alice DesRoches and Tom Gludovacz.
See you next year at Science Rendezvous!