CMMT Newsletter July 2022The Centre for Molecular Medicine and Therapeutics would like to welcome four new faculty members.
Welcome New Members!
We have EXCITING news that we would like to share with you! The Centre for Molecular Medicine and Therapeutics (CMMT) would like to welcome four new faculty members.
Their research and expertise complements perfectly the diverse work being conducted by current CMMT faculty, spanning the study of metabolomics to stem cells to epigenetics to computational and statistical methods for genomic analysis.
Jessica Dennis, Assistant Professor, Department of Medical Genetics, Faculty of Medicine, University of British Columbia
Jessica’s team works at the intersection of genetics, epidemiology, statistics, bioinformatics, and computer science to understand the biologic basis of health and disease.
Keegan Korthauer, Assistant Professor, Department of Statistics, Faculty of Science, University of British Columbia
Keegan’s group develops computational tools to translate large volumes of complex ‘omics data into interpretable molecular signals that advance understanding of cancer, child health, and development.
Seth Parker, Assistant Professor, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia
Seth’s group uses biochemical and molecular biology techniques and develops quantitative mass spectrometry-based methods to characterize the transport and fate of key metabolic fuels in diseased cells, like cancer.
Mahmoud Pouladi, Associate Professor, Department of Medical Genetics, Faculty of Medicine, University of British Columbia
Mahmoud’s team studies brain cells generated from human stem cells to understand how brain disorders develop, in order to identify new ways to treat these disorders.
Please join us in welcoming Jessica, Keegan, Seth, andMahmoud to CMMT!
If you spot them about our campus, please say hello!
Vaishnavi Sridhar: My 2022 Mini Med School Experience
Science has a greater impact when communicated to a wider public. As scientists it is very important that we spread scientific awareness, either via talks, presentations, community events, social media or other avenues. Such events not only spread scientific literacy among the public, but also motivate youth to pursue science. BC Children’s Hospital Research Institute (BCCHRI) and CMMT organize many outreach events throughout the year such as Mini Med School and the Gairdner Symposium. I have had the opportunity to volunteer for both events and discussed science with high school students. Both events involve hands on experiments, key note lectures and discussions, to give insights to high school students about what a career in life sciences and medicine has to offer.
So, after a very long time, when Mini Med School made a comeback to an in-person format, I jumped at the opportunity and signed up. Mini Med School is a health science youth outreach and public education program with a reputation for being “anything but mini.” Every course curriculum is designed to give a basic understanding of the field while exploring up-to-the-minute research, clinical applications, and social and ethical implications. Attendees have the opportunity to hear from award-winning scientists, interact with health science experts, and participate in hands-on activities.
I signed up to either discuss my research or to talk about post-secondary education and careers in science. Initially the event was to take place in Victoria and Nanaimo, however due to high demand, it expanded to the Fraser Valley. Eleven of us, graduate students from labs at BCCHRI / CMMT and faculty members, were chosen to present at the event. More than 70 high school students from 21 secondary schools and 9 cities in the Fraser Valley were expected to attend. Initially, I was chosen to speak to small groups of students about my research and experiences. However, it evolved to become a discussion with the entire group about the same, finally culminating into a 30-minute key note lecture!! Additionally, I led a foldscope, foldable paper microscope building activity (https://foldscope.com/) with two groups of students and talked about microscopy as a tool to study microorganisms.
The event was held in Chilliwack on April 8th 2022. We departed from BCCHRI / CMMT on 7th April 2022 and travelled 2 hours to reach our venue, checked in, had fun discussions over dinner, and verified that the facilities were in place for the next day’s event. The schedule included hands-on activities, fun games and quizzes organized by graduate students from different groups across BCCHRI to engage students in science in a fun way, discussing common myths about post-secondary education in medicine and keynote lectures. I got the opportunity to meet amazing fellow researchers and high school students, something that made the event an unforgettable experience.
I was scheduled to speak after lunch on the 8th. In my talk, I started off with a game asking students to tell the group what they understood about terms such as cell biology, PhD, what I routinely do in a lab and what technologies I use. This was a snowball activity, meaning students as a group would write down their answers anonymously on a piece of paper and crumple it. The snowballs were gathered and I then tossed them to attendees, asking the students to read what was in the snowball they caught. I was thoroughly impressed with their answers and have to admit that students these days are well aware of different careers!! This activity acted as an icebreaker. We next talked about cells, cellular organelles, lipid transport, why and how organelles are in contact and applications of membrane contact sites in disease. We also discussed good scientific method, model organisms and snippets from my work in the Conibear lab. I got some amazing questions from the students, including data specific questions, animal ethics, and the independence of PhD students. Overall, it was a great discussion. The event ended with one-on-one chats with the students and a photo session.
It was an incredible experience and I look forward to more events like these. The highlights for me were how much the students enjoyed my talk and their recollection of details regarding lipid transport, so much so that when we were playing a quiz and a question came up “Name some ways of transport”, the students responded with vesicular and non-vesicular transport.
Liz Conibear: Asking Big Questions
Drawn to the natural world as a child and inspired by her father’s collection of Scientific American magazines, Dr. Elizabeth Conibear’s love of nature and inherent curiosity provided the impetus for her future career in scientific research. Growing up in Ottawa, she did her undergraduate honours project in bird research on a remote island in the Atlantic Ocean. While she was keen to experience the larger world of scientific research, a career in field biology on windswept beaches turned out not to be her chosen path forward. Instead, her interest in cellular biology led her to one of the most prestigious universities in the world, where she would find a herself asking some big questions.
“As an undergrad I was always drawn to the deeper research questions in molecular biology. I wanted to make discoveries about the molecular world.” Cambridge would prove pivotal in that quest. “It was instrumental because the institution was full of Nobel Laureates,” she said. “The group leaders spoke to me in the hallways at lunchtime and discussed the latest research with me,” she said. That experience proved to be formative. “Although I was a graduate student I was treated like a real scientist,” Dr. Conibear said. “It gave me the confidence to express my views and I was taught to ask big questions there. It was fabulous. I realized I had something to say. I realized that I could make discoveries that the world cared about.”
Dr. Conibear did her graduate degree in mammalian cell culture systems at Cambridge. During that time she had interacted with many people working on model organisms like yeast and one lab in particular was making real progress. “I saw that it was possible to make great strides forward using that simple model system,” she said. “I also realized that they were advancing faster than I could with my cell culture studies.” That realization drove her to do her post-doctoral work in yeast. “I picked that model because yeast have many of the important genes that humans have but are easier to work with,” she said. This was in 1993, a time when the genome in yeast had not yet been sequenced. “The sequencing of the yeast genome was completed in 1996,” she said. “So although I started my post doc doing more old fashioned genetics, the sequencing of the yeast genome really opened up the world of genomics and yeast gave me a platform to explore technologies that previously hadn’t been available.”
Anecdotally, Dr. Conibear also picked up some robot building skills around this time. She was working in Eugene, Oregon, in what one might call pioneering times. “Towards the very end of my post doc genomics had come to the fore and we had collections of all the yeast genes knocked out in these arrayed collections that you could manipulate with robots,” she said. Not having robots readily available, Dr. Conibear found a machine in the basement gathering dust. “It turned out to be a robot, but not one that could work with yeast colonies” she said. “I went to the machine shop and got them to cut the ends of finishing nails so I could make a pinhead that was capable of transferring yeast. I didn’t invent that,” Dr. Conibear said.” At that time I was visiting Vancouver regularly from Eugene and would go through Seattle on my way. There’s a lab there that pioneered this approach. They taught me how to chop up the finishing nails,” She said. “Very out of the box, but it had to be because we didn’t have things ready-made.”
In 2002, having completed her post-doctoral degree, Dr. Conibear arrived at the CMMT, to head her own laboratory. “In coming to the CMMT, I was able to work in genomics and in yeast and get proper robots,” said. “Another wonderful thing was the exposure to the hospital site. As a graduate student in Cambridge, my lab was also embedded in a hospital setting. I really appreciated working in that environment. Your work feels more connected and more relevant. It’s valuable, especially when you do basic research like mine, where you’re interested in what the proteins do, and how mutations affect what the proteins do in disease.”
For Dr. Conibear, having her lab at the CMMT is a bit of a dream job. “I wanted to come back to Canada,” she said. “I love the pacific northwest. And, the research environment at CMMT really attracted me. There’s an attitude of striving for excellence, excitement and talking to each other that is really appealing to me.”
Dr. Conibear is quick to point out that her research is not all about yeast. “There are different aspects to my work,” she said. “Some projects in my lab work on human cells, relevant to cancer research. I really enjoy the interactions I have had here with the Hub, where clinicians can bring interesting genetic cases and get input from other researchers at BCCH.” By way of example Dr. Conibear’s research team is currently investigating the role of specialized molecules, called VPS13 proteins, in the development of a range of neurodegenerative diseases including childhood spastic ataxia. Specifically, they are investigating how these proteins work, what goes wrong on the path to disease and how this knowledge can be used to develop potential new therapies.
“Vancouver has a high concentration of people who use yeast genomics, whether it’s in cancer or in developing medicines or fundamental discoveries,” she said. “We have world experts here. Vancouver is a center both in Canada and internationally for this type of research. I appreciate that.” Ironically, the Covid 19 pandemic has helped broaden that community, with a global group of colleagues readily accessible via zoom and other digital platforms.
Today, Dr. Conibear guides the next generation of students in the way she so enjoyed at Cambridge. “As a mentor, I really want my students to have the same experience I found so pivotal,” she said. “To have the autonomy and agency to make discoveries on their own and have a voice in science.”
Judith Yan: Worms, Art and the Creative Process
It’s often been said that a good teacher can influence their students in life-changing ways, specifically their choice of careers and goals. That circumstance would certainly hold true for Judith Yan who recalls being formatively influenced by her high school biology teacher in Hong Kong where she grew up. He said that biology is going to be one of those things that will change human society in the 21st. century and I wanted to be a part of that change. True to this conviction, she chose to study molecular biology and pursue a research career in the field. An immensely curious and creative person, Judith is with the Taubert Lab where she is currently a PhD candidate in the Cell and Developmental Biology program. Her work has already produced some exciting developments on characterizing stress responses in the roundworm C. elegans.
Judith found her way to UBC and CMMT in 2019 after completing her undergraduate degree in Hong Kong and her masters at the University of Toronto. She discovered the Vancouver C. elegans community through her undergrad thesis supervisor who happened to be a UBC alumni and formerly a part of the ‘worm community’. “That’s how I learned about the exciting research taking place at UBC,” Judith said. “I knew there was a strong network of C. elegans researchers and lots of opportunities for collaboration.” She joined the Taubert Lab shortly before the outbreak of the Covid-19 pandemic.
For Judith, the global pandemic opened up a realm of new opportunities. “I mainly do wet lab work, but started doing bioinformatics projects during the pandemic, “she said. For example, she co-led the development of eVITTA (“easy Visualization and Inference Toolbox for Transcriptome Analysis”; https://tau.cmmt.ubc.ca/eVITTA/), a web app for transcriptomic data analysis. “This was originally a side project that I worked on during the lockdown,” she said. “I was scratching my head over an RNA-seq dataset that I had to analyze for my main project. This led to the idea of making a web interface that helps people analyze similar kinds of data.” Initially, the objectives of her project were twofold: first, to understand how gene expression as a whole is altered by environmental stress (particularly in starvation); and second, how these effects vary in different genetic backgrounds. “We wanted to know what happens normally in starved wildtype worms and also how things go wrong in starved mutant worms. That was a very complex comparison,” she said. “And since we were exploring broad changes, there were simply too many things for the human eye to keep track of.” The Mostafavi Lab helped Judith devise a method to tackle both problems, specifically, how two differential expression datasets could be easily plotted and compared on a scatter plot. “I self-studied Python and R, and wrote some simple scripts to turn my data into interactive plots,” she said. “We found them incredibly useful; they were easy to grasp, information-rich and visually appealing.” After taking an online course on building web apps, Judith found that she could easily wrap the scripts in an interactive web app to make them even more convenient. “I started to build some prototype web apps,” she said. “It was based on my own data to begin with, and there was no upload function. But we saw that this was a very useful tool with potential for broader applications. Our lab does a lot of RNA sequencing and we end up with massive amounts of data that are not fully explored. We realized that this tool could be useful for mining other datasets we have on hand, or even help other labs doing similar analyses.”
Dr. Jean Cheng, who co-led the eVITTA project with Judith, helped to expand the functionality of the web app. “She gave us the idea for the other two apps,” Judith said. “It grew from one module into three different web apps. The one I developed originally, easyVizR, was for visualizing and comparing multiple data sets. Later, we developed two additional apps, easyGEO and easyGSEA, which are designed for data retrieval and analysis.” At this point the developers realized that the original app, easyVizR, could also be used for comparing data from the other two apps. “In a sense, these three apps became an ecosystem or a pipeline,” Judith said.
eVITTA was published in Nucleic Acids Research. “It all had to do with Jean’s guidance, Stefan’s support, and lots of advice from others,” Judith said. She and others are still maintaining this app and adding new features. She notes that this project was one surprising way in which the pandemic has changed things in their lab. “This began as a passion project,” she said. “We had no experience making something like this. We were simply trying to share our tools and methods. We had no idea how useful it would become for the research community. A whole new field opened up for us.”
Judith’s work is driven by her love of learning and research. For her main wet-lab project, she studies the regulation of starvation responses in C. elegans. She has found that a protein that normally controls the speed of mRNA translation has a new role in protecting the cell during starvation, specifically by regulating repair of DNA damage caused by starvation. “This is important because in starvation there’s lots of reactive oxygen species, which cause spontaneous DNA damage and genomic integrity loss,” she said. “We are currently working on a manuscript about this new mechanism in the starvation response.”
In addition to being a keen scientist, Judith is also a very gifted artist: https://www.instagram.com/ema.ranth/). “I’m a naturally creative person,” Judith said. “I like imagining and making stories; this is a subjective, emotive experience, and has always been a part of the way I live,” she said. “At the same time I love science and I see research as an objective way to explore the truths of nature.” Both of these types of experiences are important to her and they help her to see the world from different perspectives. “I choose to pursue scientific research as it not only enhances my own understanding of the world but also provides a surer way to bring about meaningful change.”
Sharma M, Fu MP, Lu HY, Sharma AA, Modi BP, Michalski C, Lin S, Dalmann J, Salman A, Del Bel KL, Waqas M, Terry J, Setiadi A, Lavoie PM, Wasserman WW, Mwenifumbo J, Kobor MS, Lee AF, Kuchenbauer FC, Lehman A, Cheng S, Cooper AP, Patel MS, Turvey SE, 2022, “Human complete NFAT1 deficiency causes a triad of joint contractures, osteochondromas, and B cell malignancy”, Blood, In Press. (PMID: 35789258)
Elliott AM, Adam S, du Souich C, Lehman A, Nelson TN, van Karnebeek C, Alderman E, Armstrong L, Aubertin G, Blood K, Boelman C, Boerkoel C, Bretherick K, Brown L, Chijiwa C, Clarke L, Couse M, Creighton S, Watts-Dickens A, Gibson WT, Gill H, Tarailo-Graovac M, Hamilton S, Heran H, Horvath G, Huang L, Hulait GK, Koehn D, Lee HK, Lewis S, Lopez E, Louie K, Niederhoffer K, Matthews A, Meagher K, Peng JJ, Patel MS, Race S, Richmond P, Rupps R, Salvarinova R, Seath K, Selby K, Steinraths M, Stockler S, Tang K, Tyson C, van Allen M, Wasserman W, Mwenifumbo J, Friedman JM, 2022, “Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study”, Human Genetics and Genomics Advances, 3, 100108. (PMID: 35599849) [BCCH Foundation, Genome BC, PHSA and BC Women’s Hospital acknowledged]
Correard S, Hewitson B, van der Lee R, Wasserman WW, 2022, “RevUP, an online scoring system for regulatory variants implicated in rare diseases”, Bioinformatics, 38, 2665 – 2666. (PMID: 35289834) [NSERC, BCCHF/BCCHRI, NOW & ZONMW acknowledged]
Cheng X, Liu X, Wang J, Chen Y, Robertson AG, Zhang X, Jones SJM, Taubert S, 2022, “cSurvival: a web resource for biomarker interactions in cancer outcomes and in cell lines”, Briefing in Bioinformatics, 23(3):bbac090. Link.
Doering KRS,Cheng X, Milburn L, Ratnappan R, Ghazi A, Miller DL, Taubert S, 2022, “Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans. Elife 11:e67911. Link.
Horvath S., Lin D.T.S., Kobor M.S., Coller J.A., Said J.W., Morgello S., Singer E., Yong W.H., Jamieson B.D., and Levine A. (2022) HIV, Pathology and Epigenetic Age Acceleration in Different Human Tissues. Geroscience. 44:1609-1620.
Hernández Cordero A.I., Yang C.X., Yang J., Horvath S., Shaipanich T., MacIsaac J., Lin D.T.S., Kobor M.S., Guillemi S., Harris M., Lam W., Lam S., Montaner J., Paul Man S.F., Sin D.D., and Leung J.M. (2022) Airway Aging and Methylation Disruptions in HIV-associated Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. doi: 10.1164/rccm.202106-1440OC. Online ahead of print.
Pan H., Tan P.F., Lim I.Y., Huan J., Teh A.L., Chen L., Gong M., Tin F., Mir S.A., Narasimhan K., Chan J.K.Y., Tan K.H., Kobor M.S., Meikle P.J., Wenk M.R., Chong Y.S., Eriksson J.G., Gluckman P.D., and Karnani N. (2022) Integrative Mutli-Omics Database (iMOMdb) of Asian Pregant Women. Hum Mol Genet. doi:10.1093/hmg/ddac079. Online ahead of print.
Christensen G.M., Rowcliffe C., Chen J., Vanker A., Koen N., Jones M.J., Gladish N., Hoffman N., Donald K.A., Wedderburn C.J., Kobor M.S., Zar H.J., Stein D.J., and Hüls A. (2022) In-utero Exposure to Indoor Air Pollution or Tobacco Smoke and Cognitive Development in a South African Birth Cohort Study. Sci Total Environ. 833:155394.
Schaffner S.L., Wassouf Z., Lazaro D.F., Xylaki M., Gladish N., Lin D.T.S., MacIsaac J., Ramadori K., Hentrich T., Schulze-Hentrich J.M., Outeiro T.F., and Kobor M.S. (2022) Alpha-synuclein Overexpression Induces Epigenomic Dysregulation of Glutamate Signaling and Locomotor Pathways. Hum Mol Genet. ddac104. doi: 10.1093/hmg/ddac104. Online ahead of print.
Kuzawa C.W., Ryan C.P., Adair L.S., Lee N.R., Carba D.B., MacIsaac J.L., Dever K., Atashzay P., Kobor M.S., and McDade T.W. (2022) Birth Weight and Maternal Energy Status During Pregnancy as Predictors of Epigenetic Age Acceleration in Young Adults from Metropolitan Cebu, Philippines. Epigenetics. 1-11. doi: 10.1080/15592294.2022.2070105. Online ahead of print.
Ryan C.P., Rege R.J., Lee N.R., Carba D.B., Kobor M.S., MacIsaac J.L., Lin D.S., Atashzay P., and Kuzawa CW. (2022) Maternal Epigenetic Clocks Measured During Pregnancy Do Not Predict Gestational Age at Delivery or Offspring Birth Outcomes: A Replication Study in Metropolitan Cebu, Philippines. Clin Epigenetics. 14:78.
Posseme C., Llibre A., Charbit B., Bondet V., Rouilly V., Saint-André V., Boussier J., Bergstedt J., Smith N., Townsend L., Sugrue J.A., Ní Cheallaigh C., Conlon N., Rotival M., Kobor M.S., Mottez E., Pol S., Patin E., Albert M.L., Quintana-Murci L., Duffy D.; Milieu Intérieur Consortium. (2022) Early IFNβ Secretion Determines Variable Downstream IL-12p70 Responses Upon TLR4 Activation. Cell Rep.39:110989.
Sharma M., Fu M.P., Lu H.Y., Sharma A.A., Modi B.P., Michalski C., Lin S., Dalmann J., Salman A., Del Bel K.L., Waqas M., Terry J., Setiadi A., Lavoie P.M., Wasserman W.W., Mwenifumbo J., Kobor M.S., Lee A.F., Kuchenbauer F.C., Lehman A., Cheng S., Cooper A.P., Patel M.S., and Turvey S.E. (2022) Human Complete NFAT1 Deficiency Causes a Triad of Joint Contractures, Osteochondromas, and B Cell Malignancy. Blood. doi: 10.1182/blood.2022015674. Online ahead of print.
Pardis Kazemian | Leavitt Lab – NanoMedicines Innovation Network (NMIN) Master’s Salary Award “CRISPR/Cas9 knockdown of GNAO1 using lipid nanoparticles as a delivery system”
Sarah Thomson | Leavitt Lab – NanoMedicines Innovation Network (NMIN) Doctoral Salary Award “Lipid nanoparticle-enabled CRISPR-based gene therapy for Huntington’s disease treatment”
Laura Chan | Leavitt lab – BCCHR Doctoral Salary Award “Investigating Huntingtin Gene Mutations in Brain development”
Muna Abedrabbo | Leavitt Lab – BCCHR Brain, Behaviour and Development Master’s Studentship – “Development of an Antisense Oligonucleotide-based therapeutic approach for Pyridoxine-dependent Epilepsy”
Tiffany Chang | Taubert Lab – BCCHRI Summer Studentship “Role of Mediator subunit Med15 in cancer cell growth and stress resistance”
Leo Xu | Taubert Lab – NSERC USRA “Investigation of the role of Lipid Metabolism in the skin-like hypodermis of C. Elegans during starvation”
Donna Seraj | Taubert Lab – FoM SSRP “Dissecting the role of efk-1/eEF2K in resistance to starvation-induced oxidative DNA damage”
Judith Yan | Taubert Lab – BCCHRI Jan M. Friedman Graduate Studentship “Dissecting the Mechanisms of efk-1/eEF2K-mediated Starvation Survival in C. elegans”
Samuel Salitra | Wasserman Lab – BCCRHI Summer Studentship “Implementing a Knowledge Graph Representation of Human Transcription-Factor Information”
Save The Date
Gairdner Symposium 2022 will be held in person on Monday, October 24!
Thank you to Hilary Brewis and the CMMT Social Committee for organizing this year’s Summer Social Event!
Did you know that July was named after Julius Caesar while August was named after Rome’s first emperor, Augustus?
Daddy Yankee was the 1st Latin artist to become Number One on Spotify.
Jupiter’s magnetosphere is the largest object in the solar system. If it glowed in wavelengths visible to the eye, it would appear two to three times the size of the Sun.
AND don’t forget – Monday, August 1 is B.C Day!
Our next newsletter will be released September 2022.
Submit storyline suggestions to email@example.com by September 15, 2022.
Submit awards, events, publications, kudos, etc. to firstname.lastname@example.org by September 15, 2022.