Global Biodata Coalition designates UofT's Bio-Analytic Resource as a Global Core Biodata Resource
The Bio-Analytic Resource for Plant Biology is thrilled to have been designated as a Global Core Biodata Resource by the Global Biodata Coalition.
The Bio-Analytic Resource (BAR) at bar.utoronto.ca encompasses and provides visualization tools for large ‘omics data sets from plants. The BAR covers data from Arabidopsis, Medicago truncatula, rice, wheat, barley and 27 other plant species (with data for 3 others to be released soon).
These data include nucleotide and protein sequence data, gene expression data, protein-protein and protein-DNA interactions, protein structures, subcellular localizations, and polymorphisms. The data are stored in more than 200 relational databases holding 186 GB of data and are presented to the user via web apps.
These web apps provide data analysis and visualization tools that are hosted on the BAR. Some of the most popular tools are eFP (“electronic fluorescent pictograph”) Browsers, ePlants, and ThaleMine (an Arabidopsis-specific instance of InterMine). The BAR receives about 4 million page views a month by plant researchers worldwide.
The BAR is maintained and operated by the Provart Lab at the University of Toronto. Nicholas Provart is a professor of Plant Cyberinfrastructure and Systems Biology and is chair of the Department of Cell & Systems Biology at the University of Toronto. He has published 128 papers/book chapters/patents and been cited 18,395 times, with an H-index of 53 as calculated by Google Scholar. The BAR’s bioinformatician is Asher Pasha, and undergraduate student support is provided by Vincent Lau.
The Provart Lab has worked collaboratively with researchers around the world to develop the 157 “electronic fluorescent pictograph” views for visualizing expression data in our collection of eFP Browsers and ePlants. The effort is substantial, so much so that we are co-authors on 43 of the 60 papers that are considered BAR publications. These 60 BAR papers have collectively been cited 11,011 times since the BAR went online in 2003.
Several international resources link to the BAR and also serve up BAR expression pictographs (“eFP images”), such as TAIR, SoyBase, and MaizeGDB. In terms of experiential learning, 79 undergraduate students – mostly from the University of Toronto – have undertaken undergraduate research projects in the Provart Lab that have supported the BAR, either through tool building, data set analysis, or algorithm development. Twenty-five of these are co-authors on BAR publications, along with a further 25 trainees from the Provart Lab.
In the past 5 years, continued operation of the BAR has been ensured by grants from Genome Canada/Ontario Genomics (OGI-162) and NSERC. This funding has been supplemented by pedagogy grants and a research stipend from the Faculty of Arts and Science at the University of Toronto to Nicholas Provart for his role as departmental chair.
The staff at the BAR note: "We also very much appreciate all the cool data sets from researchers around the world to which we have been able to facilitate access!"
Connaught Award for aquatic VR to understand neural dynamics
A Connaught New Researcher Award to CSB Professor Qian Lin will combine engineering, neuroscience, game design and AI to reveal new insights on how the brain controls movement through space.
In an aquarium in Lin's lab, a fish sees two paths and swishes its tail to take the left path. A sensor catches the movement and the fish sees its environment change. Fish neurons participating in this trained decision glow and the light is captured by a multi-photon camera focused on its brain. The neural activity is then analyzed using machine learning to identify patterns involving specific neurons.
The path in the aquarium is a virtual reality (VR) projection built using the Unity game engine, and the fish’s tail is its game controller. Lin has engineered a prototype for this VR rig, but support from the Connaught Fund will allow her team to construct a more advanced and reliable platform for training fish.
Zebrafish are a well studied model animal with a 1mm thick juvenile brain that is transparent to a multi-photon microscope. Zebrafish in Lin’s lab will be trained from a young age to memorize a path in VR and the glowing activity of juvenile trained neurons will be imaged.
Previously, fish were trained to avoid a path through electric currents, but Prof Lin’s experiments will test rewarding the fish with chemical treats (adenosine triphosphate) for following the correct path.
Navigating a path depend on the communication of multiple brain regions, which develops as a function of experience. The neural dynamics that support these cognitive behaviours and the underlying neural mechanisms are unclear.
“We will extract neural activity from our imaging data and use machine learning/AI tools or factor analysis to reveal the latent dynamics,” explains Lin. “Clustering analysis categorizes the neurons into different functional groups and we use either nonlinear or linear dimension reduction, to help us to visualize and interpret the neural dynamics.”
By observing how multiple brain regions communicate through the cerebellum as part of cognitive behaviour, Prof Lin aims to build a systems map of spatial-encoding neurons that respond to cognitive inputs.
“The fish brain is much less complex than the human brain, so we can assess details of cognition in fewer neurons,” explains Lin “If the computational principles we find in one animal model have general meaning, they can be applied to other animal models including human as well, just at a different scale.”
Congratulations, Professor Qian Lin!
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.
CSB is grateful to Professors Godt and Winklbauer and other Emeritus Professors for generously providing initial funding for the CSB Emeriti Graduate Scholarship of Excellence, which is still open for contributions.
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.”
We look forward to future advice and visits to Departmental functions from Tamar and our distinguished Emeritus Professors.
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!