Big Picture Thinking
It’s hard not to be impressed by Dr. Michael Kobor. At once down to earth with a good sense of humour, he is a scientist known for his out of the box thinking. He began his career studying chromatin biology in model organisms (specifically S. cerevisiae) and has since expanded his research program to answer critical questions about human population epigenetics. Today he heads up one of the larger labs at the CMMT, with some 70 collaborative projects ongoing globally. He credits the success of his lab to the atmosphere, energy and people engaged in the research. “Our lab reflects our society,” Dr. Kobor said. “It’s very multicultural and provides a home for people with a passion for science, who are on a journey of discovery, who have a thirst or adventurous spirit to explore areas that are not quite mainstream.”
A main area of research in the Kobor Lab is human and social epigenetics, which focuses on the effects of the social environment and experience on gene regulation and how, in turn, this affects human health over the course of a lifetime. “With our research we try to understand how genes and environment interact at the level of gene expression and epigenetics,” Dr. Kobor said. One of the central themes is how early life experiences get “under the skin” and affect life and behaviour across the lifespan. “For example, what are the potential interactions with the way our genes are expressed in children growing up in poverty or in stressful family environments?” he asked. “What are the potential health outcomes? And what are the determinants of living a long and healthy life? How and to what extent does the environment interact with our genes?” As part of that research, Dr. Kobor leads the Social Exposome Research Cluster in Canada and worldwide, the long-term goal of which is to apply this knowledge to the development of interventions and policies to reduce disparities and optimize the health and well-being of all children in Canada and abroad.
The other key area of research involves model organisms with a focus on chromatin structures. Specifically, Dr. Kobor’s lab is searching for mechanisms responsible for the creation, regulation, and maintenance of chromatin signatures. These lines of inquiry include how distinct chromosomal neighbourhoods are established, how they function and interact with enzymes involved in DNA metabolism, what functional differences exist between histone variants and canonical histones, and how chromatin-remodeling complexes are regulated.
“We started in CMMT in 2005 entirely as a yeast basic research lab,” Dr. Kobor said. “Now, nearly 16 years later, we still do quite a bit of basic yeast research but have also done quite a bit of human epigenetic research. In the process we have become extremely interdisciplinary and broad in our reach in that we look from society to cell and from prenatal to people who are more than 100 years in age.”
Quick to give credit where due, Dr. Kobor emphasizes that the only way in which his lab can successfully take on the type and number of projects they do, is by having such dedicated people, from researchers to staff. “Everyone in the lab, from undergraduates to senior research associates, are living the culture of taking ownership of the projects and running with them,” he said. “It’s very interdisciplinary and what makes it so much fun is the atmosphere that we cultivate in our lab, we want people to take intellectual ownership of their projects.”
The weekly meetings are just one example of how multidisciplinary their scope is, where science is presented on everything from people looking at the association of epigenetics with child development and healthy aging, to yeast studies, to Parkinson’s disease, and to other exciting topics. “This makes it such a rich environment but it also takes a special person to flourish in this. It’s extremely interesting,” he said.
Dr. Kobor also credits his success to Dr. Hayden pushing him early on. “I can easily trace back a lot of things we do now to the director at the time, Michael Hayden, challenging me to give grand rounds in Pediatrics over at BC Children’s Hospital in 2006, just after we arrived in 2005.” “Michael said ‘you’re a big thinker, a broad thinker, why don’t you give grand rounds to the pediatricians.’ “
Having given that suggestion some consideration, Dr. Kobor suspected the pediatricians may not be too excited to hear about yeast epigenetic research so he put together a presentation about early life childhood experiences and the epigenome. “Some of the connections I made as part of the presentation were instrumental in getting the laboratory established. I always trace the success back to that particular challenge set by Dr. Hayden,” he said.
“I don’t think there would be many other places, even early in my career, that would have allowed me to stretch my own boundaries and imagination and have provided me with the liberty and support with which to do so,” Dr. Kobor said. “That’s what makes CMMT so special. We are a community that thinks outside the box and it is more appreciated, supported and expected here than other places.
Thinking in terms of how environments effect outcomes, or society to cell, one can only conclude that the effect of the environment at CMMT on the life course of the Kobor lab is positive, nurturing and hugely beneficial in the big picture.
Jack of All Trades
Hired as a lab manager in 1997, before the existing CMMT space had even been built, Michael Hockertz has not only seen the CMMT take shape, literally, he’s also done a lot of the heavy lifting involved in getting it to where it is today. His official title is Director, Core Facilities. When asked what that entails, precisely, he replied “I do whatever needs to be done at the time.” From buying pizza and treats for the original Friday afternoon seminar series back in the day, to video production, to learning AutoCAD and designing the 8,000 square foot CPNDS Pharmacogenomics facility in just 2 weeks. And of course, managing CMMT’s core facilities and shared equipment. Not your run of the mill job it seems.
“For example, when Dr Hayden hosted the World Congress on Huntington’s Disease (HD) in 2009, I got involved in the production of a unique daily recap of the proceedings in the format of a news broadcast”. The daily recap was an idea pioneered at the HD Congress meeting involving Jeff Carroll and Ed Wild, trainees in the Michael Hayden and Sarah Tabrizi labs, and led to the creation of HD Buzz: https://en.hdbuzz.net/. Charles Sabine, a former NBC journalist and war correspondent who has HD, would present a summary of the day’s proceedings together with CMMT’s two commentators, Jeff and Ed, who stood on either side of him. “One camera focused on him and the other went back and forth between the two commentators,” Michael explained. However, the production company only sent Michael the raw video at the end of each day, which didn’t make for easy viewing. “So I had to learn how to do video editing in order to create something that made sense and that we could post online. That was interesting. I knew a bit about video editing but I had to step up my skills.”
Having set up his own MS-Access database for purchasing supplies as a lab manager, Michael’s skills were also put to use to help set up the CMMT Stores. “One of Dr. Hayden’s postdocs commented that we didn’t have a science store onsite and that we should set something up. The decision was made to do this, and based on the system I’d set up for my lab purchases, I set up the point of sale system that we still use today. A group from the CMMT Team worked together to hire a Stores Manager, who is still in that role, buy the initial inventory, find suitable space, and get the entire project up and running. Soon after that, in 2000, Michael moved from the lab manager role to the Director of Core Facilities.
Shortly afterwards the DNA sequencing facility was added, which had originally been run out of Dr. Hayden’s lab. “We bought a new sequencer and started that up as a core service to meet onsite needs,” Michael said. In 1999, the CMMT animal facility was established. “We also have a transgenic mouse facility on this campus. I became involved on the finance and facilities side of that,” Michael said. In 2003 they doubled the size of that facility with a Canada Foundation for Innovation (CFI) funded project that was led by Dr. Elizabeth Simpson. “A team of us worked with the engineers to come up with the designs, order equipment, and get things in order,” he said. “There were a wide range of different tasks to do for that project, one of the more unusual and challenging of which was eventually having to re-program the HVAC system for the facility.” “Then, in 2004, together with Dr. Wasserman, we wrote a grant and secured the funding for a bioanalyzer that we continue to operate today as a core facility.”
In 2008 Dr. Hayden received a $10 million CFI grant to build and equip the Canadian Pharmacogenomic Network for Drug Safety. Dr. Hayden asked Michael to manage the project. Not a simple task. Add to that the fact that in order to take advantage of a cost savings opportunity, Michael had just two weeks to get to grips with AutoCAD and design the 8,000 square foot space on the 3rd floor of the Translational Research Building (TRB) in the BCCHRI. This included lab space, equipment rooms, isolated genomics research space, office space, two seminar rooms and a kitchen break area incorporated into the existing building facilities. “That was September, construction started in January and was finished in the summer,” Michael said. “Then we had to purchase all the equipment. This included some sample and liquid handling robotics systems so I did the methods development for those, as I’m a bit of a programmer,” he said. Whatever needs to be done. There’s a theme emerging here.
In 2014, Dr. Elizabeth Conibear received a CFI grant to purchase a state-of-the-art super-resolution confocal imaging microscope and Michael worked with her team to purchase and prepare the site for that system. “I then set up booking and billing systems for the service to enable training and access to the system,” he said. “By setting the system up as the CMMT Imaging Core, we’ve enabled this access and will use user fees to service and maintain the equipment”.
Michael now manages the monthly billing and, depending on the facility, various aspects of the financial and day to day operations of the five core facilities at the CMMT as well as continuing to manage use and maintenance of some of CMMT’s shared resources and equipment. “What I do is whatever needs to be done at the time,” he said. “I jump in, get my hands dirty doing a bunch of different things. I’m a jack of all trades in a way,” he said.
Michael’s technical knowledge helps in a variety of other ways as well. “I know enough HTML that I can look after our facility websites. I’m also pretty good at using tools such as MS-Access and MS-Excel to help people with their data analysis and management issues.”
Let’s not forget that he was the pizza guy. “When we used to do our Friday afternoon seminar series on site, I’d buy the pizza and treats and set it up,” he said. CMMT trainees restarted this initiative as the CMM Talks Seminar Series last year during the pandemic.
What’s the current project? As you might expect, a host of things. For the last couple of years, in the spirit of doing what needs to be done, he covers for both Stores and the DNA Sequencing Facility. “I aim for our services to continue uninterrupted and to not leave too big a mess when I cover in Stores or Sequencing” he said.
On the CMMT website, Core Facilities is described as: “Essential to the vision of CMMT is the creation, maintenance, and constant enhancement of an outstanding research environment equipped with state-of-the-art technology.” After learning so much, it is possible to reasonably argue that Michael may just be a Core Facility.
Biobanking – A Network of Cooperation
Stephanie Bortnick is one of those people whose career is a mixture of hard work and being in the right place at the right time. In January of this year she became the Huntington Disease (HD) BioBank Coordinator in the Hayden Laboratory at UBC’s (University of British Columbia) Centre for Molecular Medicine and Therapeutics (CMMT). “My interest in biobanks began in another lab at UBC that also had an assortment of biological samples from people from all over the world,” she said. “People make these biobank donations in the hope that it will lead to treatments and better understanding of illnesses,” she said. Stephanie took it upon herself to revamp the biobank which contained approximately 50,000 samples. “I started with one small freezer and it just grew. It was an epic undertaking that took me about two years,” she said. The work involved getting clinical and sample information into a secure database that could track the use of the samples. “I inadvertently created a biobank coordinator role for myself at that job,” she said.
When Stephanie had her first child she realized she needed part-time work in order to spend more time with her son and she found that opportunity in Dr. Michael Hayden’s lab as a part-time lab manager. Part of her role as the lab manager involved helping maintain Dr. Hayden & Dr. Leavitt’s CMMT HD BioBank. Dr. Hayden started the HD Biobank in the early 1980s and today it is one of the largest HD brain banks in the world. “Patients from all over the world have reached out to him because he is so well known and respected in the field of HD research,” Stephanie said. “While the BioBank was well organized, it needed dedicated personnel and Stephanie works closely with Jennifer Collins, Clinical Coordinator, who has played an integral role with the HD brain bank and other Hayden Lab team members to further the BioBank project. “We are also fortunate to be on the BC Children’s Hospital site where there is extensive experience in tissue banking at the BC Children’s Hospital Biobank”.
Last year, while Stephanie was on maternity leave with her second child, Dr. Hayden decided to further advance the work of the HD BioBank by raising funding for the bank from private donors. “He knows that researchers worldwide would make use of the samples if they had access,” she said. “Dr. Hayden decided to improve the BioBank, recruit additional samples, and create a website for the BioBank. His vision would require a BioBank Coordinator, someone to oversee all aspects of the project.” Upon her return from maternity leave, Dr. Hayden asked Stephanie if she would be interested in leading this project. “We have a great team to help him advance the Biobank,” she said.
Today, the CMMT HD BioBank holds nearly 1500 individual brain and peripheral tissue samples from over 200 HD patients and approximately 60 healthy ‘control’ subjects, including both fresh frozen and formalin fixed tissues. The CMMT HD Biobank is comprised of a brain bank, DNA bank, and peripheral tissues bank. While the number and types of tissues vary greatly, more than 20 different brain structures have been isolated and collected ranging from cortex to basal ganglia to cerebellum. The assortment of peripheral tissues includes spinal cord, heart, liver, spleen and testes. In addition, the HD Biobank has also collected fibroblast and lymphoblast cell lines, sperm samples and cerebrospinal fluids.
The DNA portion of the CMMT HD BioBank consists of a collection of more than 5500 DNA samples from 1000 unrelated families and 750 single unrelated individuals. The collection includes over 2500 DNA samples confirmed to carry the HD mutation, as well as approximately 1700 samples without the HD mutation. The ethnic breakdown of the collection reflects the composition of the Canadian HD population, being primarily (88%) of European origin. The remaining non-European samples are a diverse group collected both locally and through international collaborations.
The samples most researchers are interested in are brain donations. Over the past few decades, research has demonstrated that the study of human brain tissue is critical for a more comprehensive understanding of the pathogenesis of the disease. While animal studies are certainly important to HD research, it is crucial to validate the findings in HD brain tissue from HD patients as well. Brain donations are a precious and an invaluable gift to research and they are of critical importance for improving the understanding of brain disorders such as HD. Stephanie likens these donations to planting trees: “I love that saying, ‘when you plant a tree you don’t plant it for yourself but for future generations.’ The HD biobank gives HD patients and their family members the opportunity to make a unique gift in the hopes of eventually developing an effective treatment for future generations.”
We are setting up a system, a website and information pamphlets to let HD families and HD researchers know about the CMMT HD BioBank. We are also working with the HSC (Huntington Society of Canada) to raise awareness of this opportunity. Donors who are interested in partnering with us can access the process through appropriate consent and the costs of these donations will be covered by the CMMT HD BioBank project.”
Logistically, Stephanie admits it’s a lot of work but she’s passionate about it. “I’ve had to grow a lot in this role but it is incredibly rewarding to help bring Dr. Hayden’s and Dr. Leavitt’s vision of the CMMT HD Biobank to life and partner with the HD community, nationally and globally.”
Government of Canada creates national training platform for patient-oriented research
(SPOR National Training Entity)
PIs: Dr. Annie LeBlanc, Université Laval, Dr. Daniel Goldowitz, The University of British Columbia
June 23, 2021 – Ottawa, Ontario – Canadian Institutes of Health Research
- To strengthen the environment for POR in Canada, the President of the Treasury Board, the Honourable Jean-Yves Duclos, on behalf of the Honourable Patty Hajdu, Minister of Health, announced a new investment of $5.25 million over six years. This funding will support a new platform, based at Université Laval in Quebec City but active across the country.
- The new platform will increase capacity in patient-oriented research by bringing together patients, researchers, mentors, trainees, Indigenous communities, health care professionals, and health system administrators to advance the way patient-oriented research training and mentoring is done in Canada.
Dr. Michael Kobor for being appointed to the Council of Champions of Children First Canada.
The Council of Champions includes Canada’s leading voices for children’s rights and wellbeing. This diverse mix of leaders from across the country speaks as a united voice for Canada’s children, working together to urgently drive action through public awareness raising, public policy influence, research and public engagement. The Council also provides guidance on the strategic direction and priorities for Children First, and act as champions for specific projects and activities that promote the wellbeing of Canada’s children.
Dr. Elizabeth M. Simpson – BCCH CHIPS (Child Health Integrative Partnership Strategy Committee) for “Enabling CRISPR-Based Therapies for Children by means of Humanized Mice”
Co-Apps – Dr. William Gibson / Dr. Christopher Lyons / Dr. Ramona Salvarinova
Rachel Spencer (Taubert Lab) – the Canada Graduate Studies (CGS) Master’s award.
Cheng X, Yan J, Liu Y, Wang J, Taubert S. eVITTA: a web-based visualization and inference toolbox for transcriptome analysis. Nucleic Acids Res. 2021 Jul 2;49(W1):W207-W215. doi: 10.1093/nar/gkab366. PMID: 34019643
Caron NS, Anderson C, Findlay Black H, Saunders SS, Lemarié FL, Doty CN, Hayden MR. Reliable Resolution of Full-Length Huntingtin Alleles by Quantitative Immunoblotting. J Huntington Dis. 2021 Jun 4. doi: 10.3233/JHD-200463. Online ahead of print. PMID: 34092649
Galvan A, Petkau TL, Hill AM, Korecki AJ, Lu G, Choi D, Rahman K, Simpson EM, Leavitt BR, Smith Y. Intracerebroventricular Administration of AAV9-PHP.B SYN1-EmGFP Induces Widespread Transgene Expression in the Mouse and Monkey Central Nervous System. Hum Gene Ther. 2021 Jun;32(11-12):599-615. doi: 10.1089/hum.2020.301. Epub 2021 Jun 1. PMID: 33860682.
Korecki AJ, Cueva-Vargas JL, Fornes O, Agostinone J, Farkas RA, Hickmott JW, Lam SL, Mathelier A, Zhou M, Wasserman WW, Di Polo A, Simpson EM. Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells. Gene Ther. 2021 Jun;28(6):351-372. PMID: 33531684https://twitter.com/GeneTherapy_SN/status/1409860498884108298?s=20
Zhemkov V, Geva M, Hayden MR, Bezprozvanny I. Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases. Int J Mol Sci. 2021 Apr 15;22(8):4082. doi: 10.3390/ijms22084082. PMID: 33920913
Shenkman M, Geva M, Gershoni-Emek N, Hayden MR, Lederkremer GZ. Pridopidine reduces mutant huntingtin-induced endoplasmic reticulum stress by modulation of the Sigma-1 receptor. J Neurochem. 2021 Apr 19. doi: 10.1111/jnc.15366. Online ahead of print. PMID: 33871049
Naia L, Ly P, Mota SI, Lopes C, Maranga C, Coelho P, Gershoni-Emek N, Ankarcrona M, Geva M, Hayden MR, Rego AC. The Sigma-1 Receptor Mediates Pridopidine Rescue of Mitochondrial Function in Huntington Disease Models. Neurotherapeutics. 2021 Apr 1. doi: 10.1007/s13311-021-01022-9. Online ahead of print. PMID: 33797036
Presentations & News
The University of Alberta – FoMD Dean’s Lecture Series: From Mutations in a Few to Drugs for Many – Journey of a Physician-Scientist
A lecture by Dr. Michael Hayden, presented by the Faculty of Medicine’s Dean’s Lecture Series: Precision Health in conjunction with the Department of Medicine (June 28, 2021)
In conversation: ‘Training the trainers’ on early autism intervention in India
Vikk Dua and Dan Goldowitz discuss stigma-busting, building local capacity and helping families.
Save The Date
2021 Gairdner Symposium
Date: Monday, October 18, 2:00-3:45pm PST
Hosted by Dr. Michael Hayden, Centre for Molecular Medicine and Therapeutics, University of British Columbia
This free inspiring public live lecture will feature:
1. Dr. Mary-Claire King
Recipient of the Canada Gairdner International Award 2021
“For transforming cancer genetics and oncology with the discovery of inherited susceptibility to breast cancer due to mutation of the BRCA1 gene”
American Cancer Society Professor; Department of Medicine and Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Affiliate Member, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
2. Dr. Daniel J. Drucker
Recipient of the Canada Gairdner International Award 2021
“For research on glucagon-like peptides that has led to major advances in the treatment of Type 2 diabetes, obesity and intestinal disorders”
Professor, Department of Medicine, University of Toronto; Senior Scientist, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario
Please see Vancouver Gairdner symposium for more information.
Please see Gairdner Foundation for more information about the Gairdner Foundation.
For questions or more information, please contact Jessica at firstname.lastname@example.org
Our Vancouver event will also include:
A live virtual morning lecture/panel session where Grade 10-12 students from all over the lower mainland who are interested in medical research will be able to interact with CMMT and BC Children’s Hospital Research Institute (BCCHR) trainees. In the past, teachers have always been eager to have their students participate in this event.
Did You Know?
- Step 3 of BC’s Restart: A plan to bring us back together begun on July 1. https://www2.gov.bc.ca/gov/content/covid-19/info/restart
- July 17 is World Emoji Day. July 17 is famously displayed on the ‘calendar emoji’, which is why it was chosen as the date for World Emoji Day. The purpose of World Emoji Day is to promote the use emojis and spread the enjoyment that they bring to all of those around us.
- In August 1762, the sandwich, was created when John Montagu, the Earl of Sandwich, requested meat between two pieces of bread.
- Out of all 12 months of the year, September is spelled with the most letters. It contains nine letters, and it happens to be the ninth month of the year. No other months have the same amount of letters as their number in the calendar year.
|Our next newsletter will be published in late September 2021.|
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Submit awards, events, publications, kudos, etc. to firstname.lastname@example.org up to until September 15, 2021.
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