NEWS
PRiME researchers partner with TIAP and Amgen Inc. for biomanufacturing-focused project
PRiME Director, Dr. Shana Kelley, together with Drs. Jason Moffat and Stephane Angers, has secured investment from the TIAP-Amgen partnership program to test a high-throughput cell-screening device that can enable the engineering of cells with superior antibody bioproduction capabilities. This collaboration is one of 3 projects recently announced under a strategic partnership between Amgen Inc. and Toronto Innovation Acceleration Partners (TIAP) to transform discovery research from the University of Toronto community.
“We are delighted to be partnering with Amgen and TIAP to validate the MICS technology as a platform enabling therapeutic antibody production and we greatly appreciate the support provided by these sponsors,” says Dr. Kelley.
The Microfluidics Immunomagnetic Cell Sorter (MICS) developed in the Kelley lab uses CRISPR gene editing and new cytometric tools to isolate cells with a desired phenotype through in a high-throughput manner. The technology platform is a innovative development resulting from diverse expertise residing in the Kelley, Angers, and Moffat labs. It has potential to be an economical platform that performs faster and with greater capacity than existing Fluorescence Activated Cell Sorting (FACS) technology. In proof-of-concept work published in Nature Biomedical Engineering in 2019, the collaborative team showed that this platform could be used to screen for regulators of protein expression. MICS has promise for drug discovery and development, allowing for the targeting of extracellular, intracellular, and secreted proteins in different cancer, stem or primary cell types for comprehensive phenotypic profiling studies.
The UofT-Amgen team will use this technology platform to develop new approaches for antibody bioproduction. As antibody-based therapeutics become increasing complex, their bioproduction is increasingly challenging and new strategies are needed to allow high yields to be realized. The collaborative project aims to develop new approaches to increase the efficiency of the production of therapeutic antibodies.
Dr. John Delaney, Director of Amgen’s Research Technology Prospecting and Collaborations, added, “The Microfluidics Cell Sorting technology being developed by the Kelley lab has the potential to be an important and innovative tool in the drug discovery process. Working together with TIAP and the University of Toronto PRiME group allows for exploration of emerging innovation represented by MICS.”
PRiME Connaught Global Challenge Series: Global Perspectives to Advance Precision Medicine
To kick-off PRiME’s new global partnerships program funded by the Connaught Global Challenge Fund, we are launching the Connaught Global Challenge Series which will feature a virtual mini-symposium with each of our four partner institutions.
Opening the series next month is a two-day session with the University of California, San Francisco (UCSF), featuring investigators from both PRiME and UCSF discussing innovative research in proteostasis and high-throughput technologies advancing precision medicine.
Program details are below.
NOTE: This event has already taken place. You can watch this seminar series on PRiME’s YouTube channel.
PRiME - UCSF Mini Symposium
Tuesday December 1 & Wednesday December 2, 2020
Day 1: Chemical & Structural Biology of Proteostasis
1:00 – 1:15 Introduction to PRiME and the Connaught Global Challenge Program
1:15 – 1:35 Michelle Arkin, UCSF
Can we discover function-specific inhibitors of multifunctional enzymes like p97?
1:35 – 1:55 Lewis Kay, UofT
Why electrons and x-rays won’t solve the drug problem
2:00 – 2:20 Jason Gestwicki, UCSF
Targeting protein-protein interactions in the molecular chaperone network
2:20 – 2:40 John Rubinstein, UofT
CryoEM of drug targets in mycobacterial respiration
2:45 – 3:30 Questions & open discussion
Day 2: High Throughput Technologies to Accelerate Biology
December 2 Agenda – Michelle Arkin to moderate session
1:00 – 1:15 Introduction to PRiME and the Connaught Global Challenge Program
1:15 – 1:35 Hana El-Samad, UCSF
Biological feedback loops - an old problem and a new frontier
1:35 – 1:55 Jason Moffat, UofT
Genotype-to-phenotype maps: one core gene set at a time
2:00 – 2:20 Zev Gartner, UCSF
Building tissues to understand how tissues build themselves
2:20 – 2:40 Shana Kelley, UofT
Rare cell profiling for high-throughput biology
2:45 – 3:30 Questions & open discussion
The Second Annual PRiME Symposium
While the COVID-19 pandemic has kept us all physically apart, the need for the scientific community to convene and exchange knowledge and insight remains crucial for research advancement and innovation. To this regard, PRiME hosted its second annual symposium on October 13th, 2020 – virtually, this time around – with a stellar lineup representing the interface of academia and industry. With several hundred logged on to attend, this year’s symposium reached scientists both locally and abroad, for a stimulating afternoon discussion on topics in precision medicine.
The symposium began with opening remarks from the University of Toronto President, Dr. Meric Gertler, who acknowledged that “never before has the value of research been so central to everyone on the planet.” Lauding PRiME’s efforts to bring together an international audience, Dr. Gertler understood that while it is a huge undertaking and responsibility on the biomedical research community to solve the healthcare challenges of today, it is also “hugely energizing and exciting.” Dr. Shana Kelley, Director of PRiME, followed up those remarks with an introduction to PRiME and its mission to accelerate new scientific discoveries for precision medicine and empowering collaborations for research innovation. Now in its second year, PRiME encompasses over 70 faculty members across 15 departments at UofT with a growing repertoire of industry, community, and international partnerships, as well as continued success in fellowship funding for the next generation of trailblazing researchers. Looking ahead, PRiME hopes to work with others to strengthen the biotech ecosystem in Toronto to achieve worldwide impact.
The Keynote Speaker for the symposium was Dr. Chaitan Khosla, the Director of ChEM-H at Stanford University, whose research involves a multidisciplinary approach in elucidating the mechanism of immune sensitivity to dietary gluten in Celiac Disease and generating chemical tools for intervention towards druggable targets. His ground breaking work forges strong linkages between the basic exploration of disease mechanisms and the discovery of therapeutics for disease management. Dr. Khosla also discussed the importance of bridging the gaps between making discoveries and developing therapies that work in humans, acknowledging the efforts of Stanford ChEM-H and Stanford Medicine in providing infrastructure with support for preclinical activities to accelerate the development of innovative medicines. [Watch here]
The 2020 PRiME Fellows took centre stage next, with 2-minute lightning talks on their exciting, interdisciplinary research projects. Their projects focus on diagnostic or therapeutic solutions that will tackle a variety of diseases, ranging from fibrosis to COVID-19, using approaches in molecular biology, genomics, computational biology, and bioengineering. Summarizing research projects into 2 minutes and presenting it to a diverse audience is not an easy task, but each fellow delivered their presentation with clarity and enthusiasm. In the end, Ph.D. student Michael Saikali, in the laboratory of Dr. Carolyn Cummins and co-supervised by Dr. Henry Krause, received the most votes for the Audience Choice Award for the Fellow presentations. [Watch here]
The second half of the symposium switched gears to focus on industry, with company spotlights on two Canadian groups, Chinook Therapeutics and Repare Therapeutics, as well as a panel discussion with leaders from the private sector. Tom Frohlich, the Chief Business Officer of Chinook, talked about the company’s program in developing drugs for severe and rare kidney diseases [Watch here], while Dr. Michael Zinda, the Chief Scientific Officer of Repare, discussed their drug platform and screening approaches targeting genomic instability in cancer [Watch here]. The two were joined by Dr. Ho Cho, Senior Vice President of Bristol Myers Squibb, and Stacey Seltzer, a partner at Aisling Capital, in a panel on “Building Biotech Ecosystems” moderated by PRiME Associate Director Dr. Stéphane Angers. The group had a stimulating discussion on the physical and cultural infrastructure needed to facilitate research innovation and how to foster academic/industry relations to accelerate the translation of academic discoveries into potential industry assets. The group talked about challenges in the development of drug discovery and novel therapeutics, what Toronto can learn from established biotech ecosystems like Boston and the Bay Area, as well as how the current COVID-19 pandemic has and will affect the industry and marketplace in the long term. The panel brought a variety of perspectives from startup to big pharmaceutical to venture capital, providing a comprehensive outlook on Canada’s biotech sector and its future growth. [Watch here]
While it is unfortunate that this year’s event could not provide the in-person networking of our previous meeting, the Second Annual PRiME Symposium was an opportunity to share and engage across sectors with some of the best and brightest – both of today and tomorrow – in precision medicine. We hope to see you all next year in healthier times as we continue to build community and drive solutions in research, medicine, and healthcare.
PRiME awarded Connaught Global Challenge funding to expand global partnerships focused on next-generation precision medicine
The development of new precision medicine-focused approaches requires extensive collaboration and the integration of new technologies. The integration of expertise from across disciplines is essential to create new approaches for diagnosis and the identification of novel treatments from a more complete understanding of disease biology. As PRiME enters its second year as an Institutional Strategic Initiative at UofT, it is looking forward to establishing new partnerships worldwide to continue its cross-disciplinary approach. A huge step towards this vision of “Global Perspectives to Advance Precision Medicine” has been a 2020 Connaught Global Challenge Award to PRiME Director, Dr. Shana Kelley, and a team of PRiME members.
Global partnerships will be developed with research institutions in the USA, Europe, Israel and Asia and will leverage the strengths of PRiME in Drug Discovery. With support from the Connaught program, a suite of programs will be developed to forge partnerships with four key international universities: The Hebrew University of Jerusalem (HUJI), National University of Singapore (NUS), ETH Zürich, and the University of California, San Francisco (UCSF). These institutions have faculty members that are leaders in their fields and collective areas of research strengths that will complement the expertise that resides within PRiME to help advances occur more rapidly.
The funding will allow PRiME to establish a suite of new programming to benefit its community, primarily its trainees, at various stages of their training. While current COVID-19 restrictions make it a challenging time to be forging new international partnerships, PRiME will manage the first phase of programming virtually and then pursue in-person activities once safe travel is possible and allowed.
The PRiME Frontiers of Precision Medicine Speaker Series will bring experts from the partner institutions to share their research and expertise with open lectures for the UofT community.
The PRiME Ph.D. and PDF Exchange Program will provide trainee (graduate students and PDFs) exchange opportunities in specific research labs of partner institutions to allow hands on training in specialized technologies.
The PRiME Scholars Program for undergraduate students will be a 4-6 week program hosted at the University of Toronto to offer the opportunity for local and international students to gain hands-on experience in the labs of UofT PRiME researchers. Additional programming during the summer through the Scholars Program will include a boot camp focused on entrepreneurship in the life sciences and short modules focused on the frontiers of drug discovery and drug accessibility.
In addition to Dr. Kelley, the program leverages a multidisciplinary team including Stephane Angers and Keith Pardee (Leslie Dan Faculty of Pharmacy), Jason Moffat (Faculty of Medicine), Milica Radisic and Molly Shoichet (Faculty of Engineering), and Robert Batey and Alan Aspuru-Guzik (Faculty of Arts & Science). Additional expertise within the PRiME community will be offered to trainees to support engagement across a wide breadth of research interests. The goal is for partnerships fostered during this program to produce collaborations that will continue to build on UofT’s strengths, foster learning, and accelerate discoveries.
PRiME establishes a Trainee Advisory Committee
With the 2020-2021 academic year underway, PRiME has convened an inaugural Trainee Advisory Committee with the goal of better integrating trainee perspectives into the development of new initiatives and programming to support our trainee community.
Similar to PRiME’s Steering Committee, the Trainee Advisory Committee will have two representatives from each of the Faculties of Arts & Science, Applied Science & Engineering, Medicine, and Pharmacy. These eight trainee leaders will help to identify elements in current graduate and postdoctoral training that PRiME can address as we look to better prepare the next generation of scientists for diverse careers and interdisciplinary approach challenges.
The members of this year’s Trainee Advisory Committee are:
Faculty of Arts & Science
Geordi Frere (PhD Student, Prosser lab)
Dr. Jiaxi Peng (PDF, Wheeler lab)
Faculty of Engineering
Laura Bahlmann (PhD Student, Shoichet lab)
Dr. Marios Mejdani (PDF, Mahadevan lab)
Faculty of Medicine
Dr. Jonathan Labriola (PDF, Sidhu lab)
Nicole Revie (PhD Student, Cowen lab)
Faculty of Pharmacy
Dr. Margot Karlikow (PDF, Pardee lab)
Michael Saikali (PhD Student, Cummins lab)
One of PRiME’s key aims is to contribute to the development of graduate students and postdoctoral fellows as scientific and entrepreneurial leaders. The Trainee Advisory Committee will advise on future programming that will best address the professional needs of trainees, as well as encourage networking and collaborations between various labs, departments, and other partners. We are looking forward to working with the members of the committee and encourage our trainee community to connect with them in the coming weeks.
Team PRiME at the 2020 Terry Fox Run: One Day, Your Way
The 40th annual Marathon of Hope took place virtually on Sunday, September 20th to celebrate the remarkable Terry Fox and raise money to support cancer research. While we were not able to run together due to this year’s challenges related to COVID-19, members of the PRiME team laced up their running shoes to ensure that this great Canadian tradition lives on.
Dr. Christine Allen, Associate VP & Vice-Provost, Strategic Initiatives and PRiME faculty member, joined Team PRiME summarizing in a tweet that the run was “good healthy fun and a great cause.” Like Dr. Allen, other members of Team PRiME enlisted family members to join them in the event, asking partners and children to participate. Wei Ye, a laboratory technician in the Sidhu lab, Faculty of Medicine, ran with her husband. Wei has previously participated in charity runs and looked forward to training for the event during COVID-19. David Philpott, a graduate student in the Kelley lab, and member of the Faculty of Applied Science and Engineering, also took advantage of the run date and joined the team for 10K when his marathon scheduled for Sept 20th was cancelled.
For team members Amanda Clifford and Christine Misquitta, the motivation for participating in the Terry Fox run was more personal and provided an opportunity to raise money for cancer research. In addition to being involved in diagnostic and therapeutic research at UofT, the disease has also directly impacted their family members. Christine’s father is fighting a 5 year battle with stage 4 renal carcinoma and Amanda’s brother is an Ewing’s Sarcoma survivor, a cancer in the same family as Terry’s.
Regardless of the motivation and the distance, PRiME trainees, faculty, and friends participated in the Terry Fox Run in their own way and surpassed the Team PRiME goal of $2000 thanks to generous supporters. A big thank you to all who donated and we hope to see you all in person next year!
For anyone interested, donations can still be made.
PRiME's 2nd Annual Symposium to be held online on October 13th, 2020
This year PRiME will be holding its symposium virtually on October 13th, 2020. The online event will allow international researchers to join our local community and invited speakers for an afternoon of insightful presentations and discussions. Registration deadline is Friday, October 9th, 2020.
Program details are below. NOTE: Advanced registration is required to attend.
1:00 Opening Remarks
1:15 Welcome & PRiME overview: Shana Kelley, PRiME Director
1:30 Keynote Speaker: Chaitan Khosla, Director, ChEM-H, Stanford University
“Celiac Disease: From Drug Prototyping to Experimental Human Biology”
2:15 2020 PRiME Fellows lightning talks
BREAK
2:45 Company Spotlight 1: Chinook Therapeutics (Tom Frohlich, Chief Business Officer)
3:15 Company Spotlight 2: Repare Therapeutics (Mike Zinda, EVP & Chief Scientific Officer)
3:45 Panel discussion: Building Biotech Ecosystems
Ho Cho, Senior Vice President, Bristol Myers Squibb
Tom Frohlich, Chief Business Officer, Chinook Therapeutics
Stacey D. Seltzer, Partner, Aisling Capital
Mike Zinda, Chief Scientific Officer, Repare Therapeutics
5:00 Symposium close
Registration Deadline: Friday, October 9th, 2020
REGISTER TO ATTEND
For further information, please contact us.
2020 PRiME Fellowship Awards
The second cohort of PRiME Fellows was announced today, with nine exceptional young scientists receiving funding to conduct impactful research at the University of Toronto.
Their projects focus on diagnostic or therapeutic solutions that will tackle a variety of diseases, ranging from fibrosis to COVID-19, using approaches in molecular biology, genomics, computational biology, and bioengineering. The winners were selected by the PRiME Fellowship Committee, and showcase some of the exciting and innovative research from PRiME investigators in the Faculties of Pharmacy, Arts & Science, Medicine, and Engineering. Cross-disciplinary collaborations are a key element of PRiME’s approach to advance next-generation research solutions in precision medicine.
Now in its second year, the PRiME Fellowship competition takes place each spring and provides funding to PhD students or postdoctoral fellows with bold ideas that enable high-risk, high-reward research. Fellows will be supported by PRiME in their scientific progress for one year and assisted in leveraging further funding for the next stage of research activity in the lab. Earlier this year, PRiME also launched an Industry-Partnered Fellowship Program which accepts applications throughout the year.
The 2020 awardees are listed below in alphabetical order:
Subha Dahal, PhD Candidate
Supervisors: Drs. Alan Cochrane (Medicine) and Rebecca Laposa (Medicine)
Project title: Development of small molecule modulators of RNA processing as broad spectrum antivirals
Eric Donders, PhD Candidate
Supervisors: Drs. Molly Shoichet (Engineering), Mark Lautens (Arts & Science)
Project title: Triggering Release from Colloidal Drug Aggregates
Brendan Innes, PhD Candidate
Supervisors: Drs. Gary Bader (Medicine) and Alison McGuigan (Engineering)
Project title: Mapping macrophage-fibroblast links in hypoxic environments, focus on fibrosis
Zhongle Liu, Postdoctoral Fellow
Supervisors: Drs. Leah Cowen (Medicine) and Robert Batey (Arts & Science)
Project title: Structure-enabled design and synthesis of fungal-selective mitochondrial inhibitors
Marios Mejdani, Postdoctoral Fellow
Supervisors: Drs. Radhakrishnan Mahadevan (Engineering) and James Rini (Medicine)
Project title: COVID-19 Diagnostic & Vaccine Development Platform
Jiaxi Peng, Postdoctoral Fellow
Supervisors: Drs. Aaron Wheeler (Arts & Science) and Hui Peng (Arts & Science) and Cindi Morshead (Medicine)
Project title: Analysis of Neural Stem Cell Aging by Single-Cell Proteomics
Michael Saikali, PhD Candidate
Supervisors: Drs. Carolyn Cummins (Pharmacy) and Henry Krause (Medicine)
Project title: Targeted Temporal Quantification of Nuclear Receptors Involved in the Gut-Brain Axis
Suryasree Subramania, Postdoctoral Fellow
Supervisors: Drs. Sachdev Sidhu (Medicine) and Stephane Angers (Pharmacy)
Project title: Innovative antibody engineering technologies for targeting therapeutically relevant Frizzled co-receptors
Warren van Loggerenberg, Postdoctoral Fellow
Supervisors: Drs. Frederick Roth (Medicine) and Axel Guenther (Engineering)
Project title: A comprehensive variant effect map for CPOX
PRiME’s Industry-Partnered Fellowship Program Launches With COVID-19 Projects
Many of the trainees working with PRiME faculty members will pursue career opportunities in the life sciences sector and value the opportunity to collaborate with industry groups during their time at UofT. To create internships with industry partners for PRiME trainees, a new Fellowship Program was launched in July that will provide a framework to facilitate UofT-company partnerships and trainee internships. The new Industry-Partnered Fellowship Program leverages funding from Mitacs Programs to help provide graduate students and postdoctoral fellows the opportunity to work with industry partners of PRiME. In particular, the first two fellowships through this Program were enabled through Mitacs’ response to COVID-19, supported by both federal and provincial investments, to increase the number and types of internships available.
At PRiME, we were able to help connect our research faculty with companies that were looking for additional expertise as they expanded, or pivoted, their business models to address COVID-19. This included one diagnostic company, Cellular Analytics, that adapted its microfluidic platform from detection of cancer biomarkers to identify specific cell populations to help with COVID-19 patient stratification to predict potential responses to therapies. A second project, that is a collaboration with OptiSolve - a company that offers imaging-based analysis of cleaning effectiveness – will focus on the adaptation of the existing imaging technology to include the detection of SARS-CoV2 in a handheld device for rapid surface analysis.
Although these projects are short-term to help with the immediate needs of the pandemic, we also have additional non-COVID-19 related projects in review that will involve PDFs and students for longer terms. The opportunity to work with both small and large industry partners is invaluable for our trainee community. Given the many biotechnology- and diagnostics-driven start-ups in the local ecosystem, we look forward to building relationships to expand this Fellowship Program in the coming months.
Catching Up with the Inaugural 2019 PRiME Fellows
Last September, the first annual PRiME Fellowship Awards were presented to 10 outstanding trainees at the University of Toronto to drive forward high-risk, multidisciplinary research focused on solutions in precision medicine. Projects ranged from innovations in drug discovery to diagnostic development and improving our understanding of disease biology. As we approach the end of our first funding round, we provide a closer look at the 2019 PRiME Fellows’ year of scientific progress and success, and a preview of the exciting work that still lies ahead for these researchers.
Dr. Noor Al-saden’s project proposed to develop radiation therapy using gold nanoparticles that delivers radionuclide straight to brain tumour cells for local treatment of a fast-growing brain cancer, glioblastoma multiforme (GBM). Under the supervision of radiation nanomedicine specialist Prof. Raymond Reilly (Leslie Dan Faculty of Pharmacy) and polymer chemist Prof. Mitch Winnik (Faculty of Arts & Science), Noor has been constructing and characterizing these gold nanoparticles and began testing how effective they are in killing GBM cells in vitro. She also plans to test her therapy in mice to determine the ability of the nanoparticles to selectively kill tumour cells while leaving normal brain cells unharmed. Preliminary results from Noor’s work led to a $200,000 Canadian Cancer Society Innovation Grant awarded to Prof. Reilly’s group, for a project using radiation nanomedicine therapy in combination with current checkpoint immunotherapy for intraoperative treatment of GBM.
Dr. Rony Chidiac has been studying how Frizzled (FZD) signaling affects the permeability of the blood-brain or retinal barrier (BBB/BRB), which can deteriorate or become dysregulated in neurodegenerative disorders and retinal disease. In the past year, Rony brought together expertise in Wnt/FZD signalling from the lab of Prof. Stephane Angers (Leslie Dan Faculty of Pharmacy) with the antibody engineering knowledge of Prof. Sachdev Sidhu (Faculty of Medicine) and investigated the activation of FZD4 signaling in endothelial cells using a novel antibody-based FZD4 agonist. Next, Rony expects to test the effects of FZD4 signaling in primary endothelial cells as well as in a mouse model.
Angela Duong has been working to understand mitochondrial function and its role in neuronal activity in the laboratory of Prof. Ana Andreazza (Faculty of Medicine). With guidance and expertise from Profs. Liliana Attisano and Martin Beaulieu (both Faculty of Medicine), Angela has grown 3D in vitro cultures of brain cells (cerebral organoids) from human induced pluripotent stem cells. This was done by reversing patient blood cells into a stem cell state, and then generating cerebral organoids. She has characterized the different cell types growing in these organoids and measured the electrophysiological activity of the neurons. Additionally, she has been studying the state of the mitochondria over the course of cell differentiation and plans to examine its function in these cells by selectively knocking down or inducing different mitochondrial genes in the system.
Dr. Margot Karlikow has proposed to use gold nanoparticles to establish a sensing tool that can detect if pathogen genetic material is present in a sample. The presence of a pathogen would activate the gene-editing CRISPR tool to make DNA breaks within nanomaterials that can be detected optically. This project combines the expertise of Prof. Keith Pardee (Leslie Dan Faculty of Pharmacy) in synthetic biology with that of Prof. Gilbert Walker (Faculty of Arts & Science) in nanomedicine. Margot has already worked out a fluorescent-reporting system that senses DNA breakage and constructed the gold nanoparticle that captures the released DNA to facilitate this output. She is currently working to put all of this together and then will validate the effectiveness of this device.
Anastasia Korolj’s project aimed to diagnose recurring kidney disease after transplantation by looking at patient serum samples in a dish. Under the guidance of Prof. Milica Radisic and Prof. Axel Guenther (both Faculty of Applies Science & Engineering), Anastasia has been designing a device that contains podocyte cells which change morphology when exposed to patient samples with signs of disease. She is currently optimizing this platform and testing to validate its effectiveness in patient samples with help from Dr. Ana Konvalinka (Faculty of Medicine). The foundational work that Anastasia did as a PRiME Fellow has led to follow-on funding from NSERC and CRAFT of $150,000.
Dr. Jiabao Liu has spent the past year identifying and investigating high affinity, fatty acid binding partners for PPAR orphan receptors to understand how to better treat PPAR-related diseases. Using a myriad of approaches from metabolomics to de novo synthesis, chromatography, and circular dichroism, Jiabao was able to characterize selective ligand targets, their binding stability, and their role in neuronal function. His research contributed to a successful New Frontiers in Research Funding (Exploration) grant for $250,000 worth of funding for supervisors Profs. Henry Krause (Faculty of Medicine) and Carolyn Cummins (Leslie Dan Faculty of Pharmacy), and collaborator Prof. Hui Peng (Faculty of Arts & Science).
Dr. Mark Mabanglo sought to understand how small molecules can interact to inhibit the ClpP protease in bacteria to become effective antibiotics. Working in the laboratory of Prof. Walid Houry (Faculty of Medicine), with guidance in organic chemistry from Prof. Robert Batey (Faculty of Arts & Science), Mark grew crystals of ClpP and validated its activity in this state. Furthermore, Mark has collaborated with the labs of Drs. Peng Chen and Chu Wang at Peking University in China to design mutant variants that can be used in future studies to determine how the protein folds and functions.
Dr. Jiaxi Peng proposed to investigate the profile of proteins expressed by neural stem cells during aging. He has developed a digital microfluidics/laser-cell lysis system to accomplish this and was able to optimize its use to produce sensitive results at the single cell level at low sample concentrations. This project merged the expertise of Prof. Aaron Wheeler in microfluidics and single cell analysis with that of Prof. Hui Peng in high-resolution mass spectrometry and proteomics (both Faculty of Arts & Science). He is now using this system to better understand neurodegeneration in Huntington’s and Alzheimer’s disease.
Yuxi Xiao’s project aimed to develop a tool for studying the function of multiple genes in a high-throughput manner. Under the supervision of Prof. Jason Moffat (Faculty of Medicine), she has been establishing a pooled screening protocol using the CRISPR-Cas12a gene editing system. She has designed and performed a pilot screen to identify gRNA characteristics that result in successful gene targeting. Combined with microfluidics, with help from Prof. Shana Kelley (Leslie Dan Faculty of Pharmacy), Yuxi will continue to increase the speed and throughput of this assay to study gene interactions. The Kelley-Moffat project recently led to a UofT-industry collaboration that will bring additional resources to this effort.
Dr. Fei Xu has been developing an in vitro small-molecule drug screen using a microfluidics platform and artificial intelligence. Under the guidance of Prof. Eugenia Kumacheva (Faculty of Arts & Science), Fei has grown cancer cells on a hydrogel that can be held in three different microfluidics prototype devices that she has developed. She is currently optimizing this platform in order to determine how effective different anti-cancer drugs are in killing breast cancer cells. With expertise from Prof. Alan Aspuru-Guzik (Faculty of Arts & Science), she plans on using AI to analyze the results and further adapt her device to accommodate testing of other cell types and drug formulations. Fei’s work contributed to a successful application to the New Frontiers of Research Fund (NFRF) Exploration program resulting in a $200,000 grant to Prof. Kumacheva’s group.
Even with the unprecedented pause in research due to COVID-19, we are proud of the significant progress our Fellows have been able to achieve within this year of support from PRiME. We are looking forward to announcing the 2020 PRiME Fellows in September. With the wealth of talent here at the University, we have no doubt that the next cohort of awardees will bring equally exciting ideas and discoveries to precision medicine.