To Serge Gueroussov, it all felt “surreal”. As many times before, he was in the usual lecture room, in which the newly awarded top graduate of the year was about to deliver a lecture about their PhD research. Only this time, it was Gueroussov who was on the podium.
Gueroussov is the latest recipient of the Barbara Vivash Award in Molecular Genetics for the most outstanding PhD thesis in the University of Toronto’s Department of Molecular Genetics (MoGen).
“During my time as a graduate student, some of the people that I looked up to the most went on to win this award, so to get it myself is very humbling,” says Gueroussov who came to the award ceremony from Cambridge, MA, where he moved to for postdoctoral training.
Established in 2009, the Barbara Vivash Award in Molecular Genetics recognizes PhD research that has significantly advanced our understanding of how biological processes operate on a molecular level. Past awardees went on to have successful research careers at top universities, including University of California San Francisco, Princeton University and U of T.
The Barbara Vivash Award in Molecular Genetics was borne out of the family’s long-standing commitment to the field of genetic medicine, going back four decades to when Mrs. Barbara Vivash was involved with establishing the first clinics for genetic counselling in northern Ontario communities so their residents no longer had to travel far for expert advice.
“That early introduction to genetics certainly helped to sustain my interest in this ever expanding field of medicine,” says Mrs. Vivash. “So when my husband John and I discussed setting up an award, there was no doubt in our minds about where we wanted it to go.”
“We tremendously appreciate the support from the Vivash family with this gift, which provides important recognition of scientific excellence and promotes the success of the next generation of scientific leaders” said Professor Leah Cowen, Chair of Mogen.
Gueroussov has already been successful at every stage of his career, publishing original research from when he worked as an undergraduate in Professor Alexander Palazzo’s lab at the Department of Biochemistry. But it was his PhD work in Professor Ben Blencowe’s group in the Donnelly Centre for Cellular and Biomolecular Research that revealed groundbreaking new insights about the evolution of cellular complexity. During this time, Gueroussov published seven papers including first author studies in top journals Cell and Science. “These were absolutely stunning, really original, landmarks studies,” said Cowen.
“I am very grateful for the opportunity to do my thesis work with Ben in the collaborative environment of the Donnelly Centre”, says Gueroussov. “Ben was tremendously supportive throughout my time there and had a great sense of when I needed his mentorship and when to let me explore on my own.”
The field of medical genetics has been transformed from its fledgling roots in the last century in part due to rapid advances in DNA sequencing and data analysis. Researchers today have an unprecedented view of how cells operate on a molecular level, revealing clues about what causes disease and how best to treat them. These advances are also shedding light on the age-old question of how we as humans evolved with our advanced tool making, language, problem solving and social skills.
“Ben was tremendously supportive and had a great sense of when I needed his mentorship and when to let me explore on my own” - Serge Gueroussov
During his PhD, Gueroussov revealed one piece of this puzzle. Building up on previous work in the lab, he uncovered how a cellular process known as alternative splicing could have driven brain evolution in mammals. Alternative splicing enables cells to produce a far greater variety of proteins—the cell’s workhorses— than there are genes encoding them. Gueroussov found a molecular switch in this process that only works in the mammalian brain and which has contributed to tissue complexity and possibly also the evolution of advanced cognitive functions.
In another study, Gueroussov revealed a tantalizing possibility that one of the roles for alternative splicing in the brain might be to ward off sticky proteins that form large aggregates and are a hallmark of neurodegenerative diseases such as Parkinson’s and Alzheimer’s.
“If you have too much protein aggregation, that’s linked to neurodegenerative disorders,” Gueroussov said during the lecture. “So we could speculate that one purpose for the evolution of this splicing was to limit the extent of aggregation that was taking place.”
“Serge has made valuable contributions to our understanding of the regulation, function and evolution of alternative splicing,” says Blencowe. “He is a remarkably ambitious and gifted young scientist and I fully expect him to continue publishing groundbreaking research in the future.”
Since last September, Gueroussov has been living in Boston, where he is working as a postdoctoral fellow in the lab of Professor Feng Zhang, a celebrated researcher who was one of the first to use the gene editing tool CRISPR to edit genes in human cells, at the Broad Institute of MIT and Harvard.
“I was very excited to come here and see what my ultimate potential is as a scientist,” Gueroussov says. “So far, I am enjoying it.”
At the Broad, Gueroussov is investigating new strategies for editing not the genes, but the genes’ messages, or RNA molecules that act as protein templates. These new technologies open exciting possibilities as research tools to study RNA biology, he said.
New Cancer Immunotherapy in the Making Thanks to Antibody Engineering Technology Developed at Donnelly Centre
Author: Jovana Drinjakovic
A new therapy that enhances the body’s ability to fight cancer has received a $62-million (USD) boost thanks to Donnelly Centre's antibody engineering technology.
Called Myeloid Tuning™, the therapy is designed to boost the body’s anti-tumour immunity by removing the cells that normally put brakes on the immune system using engineered antibodies from U of T’s Toronto Recombinant Antibody Centre (TRAC).
“Instead of turning on the immune cells directly, you get rid of the cells that are inhibiting the immune cells,” says Professor Sachdev Sidhu, who co-founded TRAC with Professor Jason Moffat as a state-of-the-art antibody engineering platform at the Donnelly Centre for Cellular and Biomolecular Research, where both are faculty members.
Unlike natural antibodies produced by the immune system to fight disease, engineered antibodies can be designed to target any molecule or cell type and are becoming increasingly used in medicine as a new generation of drugs.
The work that led to myeloid tuning started five years ago as a research collaboration between Sidhu and Moffat, both also professors in U of T’s Department of Molecular Genetics, and Professor Max Krummel at the University of California San Francisco (UCSF). Krummel co-invented the first engineered immunotherapy approved in 2011 against skin cancer. Three years later, Sidhu and Krummel co-founded Pionyr Immunotherapeutics in San Francisco to turn their research idea into reality.
“It’s an example of how you can go very quickly, within a few years, from basic research to potential clinical applications,” says Sidhu.
In recent years, immunotherapy, in which the body’s immune system is awakened to destroy tumour cells, has emerged as a highly promising treatment against a range of cancers.
Last month, Pionyr announced it raised $62 million (USD) from investors bringing its total funding to $72 million (USD) raised in two years to develop myeloid tuning into a form in which it can be tested on patients. The funding boost came on the back of promising proprietary data obtained with antibodies created in Toronto. So far, myeloid tuning has been shown to be effective in multiple mouse tumour models.
Three forms of immunotherapy have been approved for use in patients to date. Checkpoint inhibitors and bispecific T-cell engagers (BiTEs) work by making cancer cells more visible to the immune system and have been approved for the treatment of skin, lung, and bladder cancer, among others. In chimeric antigen receptor T (CAR-T) cell technology, which received its first approval in the US three months ago against a form of leukemia, the immune T-cells are engineered to recognize and attack cancer more effectively.
Myeloid tuning is different in that it does not act directly either to target the cancer cells or to activate the immune T-cells. Instead, engineered antibodies are designed to attack the immunosuppressive cells in the tumour microenvironment to help the immune system sweep cancer cells more effectively.
Built from the ground up in 2010, TRAC has grown into a sought-after technology platform with more than 50 ongoing collaborations worldwide. Besides Pionyr, there’s also Saksin LifeSciences in India, a startup that is turning TRAC antibodies into new medicines for blindness.
“The TRAC has established itself as a premier protein engineering platform attracting partnerships and significant research funding from industry,” says Moffat.
Moffat and Sidhu want to see more new drugs developed in Toronto. That is being made possible thanks to additional support from the visionary philanthropist Terrence Donnelly, whose gift 13 years ago helped found the interdisciplinary biomedical research institute that now bears his name. In October, Donnelly announced a new $10-million gift to support research and innovation. That will enable the Donnelly Centre to soon launch a new hub for biotechnology startups that will accelerate translation of its research discoveries into new therapies.
“Pionyr came out of a similar biotech incubator at UCSF. Imagine what we could do if we had one here. We have thousands of high-quality antibodies that are just sitting there waiting to be turned into new drugs,” said Sidhu.
"Many of the medical breakthroughs of the last century could be lost through the spread of antimicrobial resistance. Doctors and hospitals urgently need new medicines, but the source might surprise you: high-performing academic research labs are on the front lines generating these new discoveries."
Read the full opinion piece in The Toronto Star
PhD Student Recruitment
Applications are encouraged from highly motivated students to participate in a joint PhD program in the Zhejiang University – University of Toronto (ZJU–UofT) Joint Institute of Genetics and Genomic Medicine, which was recently established between the two universities. Each student will be jointly supervised by a faculty member from ZJU and a faculty member from UofT, and will conduct approximately half of the research in Toronto and half in Hangzhou.
PhD Projects Currently Available:
- Biomolecular analysis of lung cancer
- Neural circuits and brain disorders
- Molecular genetics of neurodegenerative diseases
- Pathophysiology of mitochondrial disorders
- Role of RNA binding proteins in neural stem cells
Closing Date: April 16, 2018
It is with a heavy heart that I share the news that Dr. John Carlin Roder, FRSC, passed away on Saturday, January 6, 2018.
John held an appointment in Molecular Genetics from 1987, until his retirement. He was one of the Lunenfeld-Tanenbaum Research Institute's first scientists, recruited by Lou Siminovitch in 1985 from Queens University, and he spent over 30 years at LTRI as a Senior Scientist.
John was an amazing scientist and truly caring person. In mid-career, he decided to switch his entire scientific focus from natural killer cells and immunology to the genetics of neuroscience, and went on to become a world leader in this field.
Our deepest condolences to John’s wife, Mary-Lou, and to John's family. Canada has lost a giant in neuroscience, they have lost a most wonderful man.
- Dr. Leah Cowen, Professor & Chair
See Lunenfeld-Tanenbaum Research Institute announcement
See The Toronto Star obituary
Thursday, 30 November 2017, 5-6pm
Red Room, Donnelly Centre
160 College Street
Toronto, ON M5S 1A8
Are you interested in a career in genomics? Would you like to strengthen your professional profile with solid knowledge and skills in modern genetics? In this info session we will present the new Master's program, answer your questions, and you can meet students and faculty from the Department of Molecular Genetics at the University of Toronto.
We are looking for enthusiastic and engaged students who have either a clinical or a B.Sc. background, and who are interested in pursuing a career in medical genomics. This is a full time course-based Master’s program which takes place over 20 months. Students will become well-versed in different aspects of genomics, and will engage with renowned faculty and clinicians who are at the cutting edge of biomedical research, pharmacogenomics, and human genetics to recognize and address pressing questions in the field of medical genomics.
If you plan to attend the info event, please RSVP.
"By showcasing the achievements of top female scientists, the annual awards may encourage more women and girls to consider a career in science. Women remain underrepresented in the field, with fewer than three per cent of Nobel prizes given to women since the award’s inception."
See full article
What: Molecular Genetics M.Sc./Ph.D. Graduate Programs and Application Info Sessions
When: MON. Oct 23rd, 5-6:30 pm. , Mon. Oct 30th, 5-6:30 pm
The sessions are the same - you only need to attend one!
Where: MoGen Interacthome, Medical Sciences Building #4284, 1 King's College Circle
Come Talk with professors about how to apply and learn about a career in science!
Free pop and pizza!
RSVP required by Oct 20th
Next application deadline is Nov. 15th, 2017
The 2017 Department of Molecular Genetics Annual Retreat and Power Hour, was held September 20-22rd at YMCA Geneva Park Conference Centre on Lake Couchiching in Orillia.
The Retreat began with a Power Hour where faculty members presented their lab's research to our new rotation students in 3 minutes with one prepared slide. The remainder of the Retreat involve faculty talks and a poster session presented by faculty, students, post-docs and staff. Entertainment on Thursday evening was organized by our graduate students.
Congratulations to our Poster Prize Winners:
Duah, Kwamaa (Cowen lab), Chloe Rose (Ciruna lab), Liu, Shixuan (Kafri lab), Ashrut Narula (Rissland), Michael Pryszlak (B. Pearson lab), Daniel Witvliet (Zhen Lab) and Eesha Sharma, (Blencowe lab)
Congratulations to the Departmental Award Winners:
Harley O'Connor Mount (Ensminger Lab) - L.W. Macpherson Award
Kaitlin Laverty (Hughes/Morris Labs) - Roman Pakula Award
Dustin Ammendolia (Brummell Lab) - Norman Bethune Award
Elissa Currie (Gray-Owen Lab) - Eric Hani Fellowship
Photographs: Dr. Mikko Taipale
Author: Jovana Drinjakovic
Ten PhD candidates who come from diverse training backgrounds, and are enrolled in different U of T graduate programs, have been awarded the Cecil Yip Doctoral Research Award, the award committee has announced. The prestigious award is given annually to first year graduate students who do their doctoral research in the Donnelly Centre and whose proposed projects extend beyond traditional scientific field boundaries. This year’s successful candidates come from three U of T departments: Molecular Genetics (MoGen), Chemical Engineering and Applied Chemistry (ChemE) and the Institute of Biomaterials and Biomedical Engineering (IBBME).
“This year’s candidates exemplified the unique interdisciplinary environment and collaborative culture of the Donnelly Centre. The diverse backgrounds of the candidates, ranging from biology to engineering and philosophy, and, in some cases, extensive industrial experience, clearly demonstrates how the Donnelly Centre attracts those who are keen to work in areas outside of their comfort zone on some of the most challenging questions in biomedicine,” says Professor Christopher Yip, Associate Vice-President of International Partnerships and Chair of the Yip Doctoral Award Committee.
Benjamin Kingston, Jessica Ngai and Wayne Ngo Research at the intersection of biology and engineering has the potential to develop new methods for delivering drugs precisely when and where they are needed in order to target cancer for example, or spur on tissue regeneration to heal damage or injury. Mr. Benjamin Kingston (IBBME), Ms. Jessica Ngai (ChemE) and Mr. Wayne Ngo (IBBME) in the Chan lab are studying how tiny nanoparticles can be better engineered to deliver cancer drugs directly into tumours to avoid the all-out toxic assault on the body that typically comes with chemotherapy.
Alaura Androschuk To boost repair of nerves damaged by, say, high blood glucose that can cause diabetic patients to lose all feeling in arms and legs, Ms. Alaura Androschuk (IBBME, Sefton) is investigating if a biomaterial, previously discovered by the lab to promote healing of the muscle, can also drive nerve repair.
Investigating cellular processes in easy-to-study organisms such as yeast and worms can reveal basic principles of biology that apply to all animals but would be very hard to study in humans. To understand how cells change with age, Mr. Clarence Hue Lok Yeung (Mogen, Andrews and Boone) is investigating complex genetic networks that drive the aging process in yeast cells. And Mr. Daniel Merritt (Mogen, van der Kooy lab) is taking advantage of nematode worms as a model system for understanding the molecular basis of how animals detect smell.
One of the greatest outstanding questions in biology is how cells interpret the genetic information encoded in the DNA and its RNA copies that contain the blueprint for making proteins, the building blocks of life. The so-called RNA binding proteins (RBPs) play an important role by ensuring that an RNA message is correctly prepared before being translated into a protein, but it remains unclear how the RBPs recognize the countless RNA molecules and act on them appropriately. Mr. Alexander Sasse (Mogen, Morris) and Ms. Kaitlin Laverty (Mogen, Hughes and Morris) are tackling this problem by developing advanced computational models for predicting which RBPs bind which RNA molecules.
Proteins make up our cells and do most of the work in them by interacting with each other to carry out cellular processes. When proteins go awry—cease to interact with their normal partners and/or acquire new alliances—that’s when diseases occur. Two of this years’ Yip award winners are studying rules behind protein interaction to gain a deeper insight into basic cell biology and mechanisms of disease: Mr. Dmitri Segal (Mogen, Taipale) is uncovering binding partners for the 14-3-3- family of “scaffolding” proteins that interact with hundreds of diverse proteins to facilitate molecular events in the cell, whereas Mr. Greg Martyn (Mogen, Sidhu) is focusing on the family of SH2 proteins that are involved in a number of diseases, including cancer. Martyn will engineer SH2 superbinders, or protein fragments that bind so strongly to the SH2 proteins that they can be used to manipulate their function and as such used in research and drug development.
The award was established as a tribute to Professor Cecil Yip, who was the former Vice-Dean, Research in the Faculty of Medicine and a key player in both the ideology and eventual realization of the Donnelly Centre as an interdisciplinary institute at the forefront of biomedical research.
Cover photo: Samantha Yammine
University Professor Janet Rossant received a 2017 honorary Doctor of Science degree from Cambridge University, for her contributions to stem cell biology and other research. Dr. Rossant is a Professor in the Departments of Molecular Genetics, and Obstetrics and Gynaecology, at U of T. She is also a Senior Scientist at SickKids as well as President and Scientific Director of the Canada Gairdner Awards.
The Genetic Counselling program is pleased to announce the inaugural McLaughlin Centre, University of Toronto recipients. The McLaughlin Centre has provided funds to support two merit-based scholarships for the MSc Genetic Counselling Program. One incoming first year student will be awarded an entrance based scholarship to be granted based on overall merit including demonstrated academic excellence prior to entering the program. In addition, one second year student will be awarded an in-course scholarship based on overall academic excellence in their first year of study in the M.Sc. Genetic Counselling Program. This year each successful student will receive a $10,000 CAD scholarship.
Congratulations to incoming student Kalene van Engelen and second year student Emily Thain!
Four of the Fifteen University of Toronto faculty members named Canada Research Chairs are members of the Department of Molecular Genetics. In addition, 13 Canada Research Chairs were renewed, including 3 from Molecular Genetics.