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An E-Newsletter From
The TRanslational Initiative to DE-Risk NeuroTherapeutics (TRIDENT)
The TRanslational Initiative to DE-risk NeuroTherapeutics (TRIDENT) draws upon research supported by the Government of Canada’s New Frontiers in Research Fund - Transformation stream (NFRF-T). Headquartered at Western University, London, Ontario, TRIDENT is led by teams of experts across leading Canadian research institutions, including the Centre for Addiction and Mental Health (CAMH), the Douglas Research Centre, McGill University, the Neuro, and
the University of Toronto. By offering a transformative approach to preclinical evaluation of neurotherapeutics, TRIDENT will dramatically improve the odds of success of neurotherapeutics in clinical trials for the benefit of humans
across the globe.
From the TRIDENT
Principal Investigator
As we move through another exciting year for TRIDENT, I continue to be inspired by the dedication, creativity, and collaborative spirit of our students, trainees, staff, faculty, and partners across the platform. This newsletter highlights some of the many accomplishments made possible through your hard work, from promising research advances across our cores to new partnerships, outreach activities, and growing opportunities for collaboration. This year marks an important milestone for TRIDENT as we prepare for our NFRF Transformation midterm grant review. Over the past three years, we have built an extraordinary national platform designed to de-risk and accelerate neurotherapeutic development, and the months ahead will provide an opportunity to reflect
on our progress, showcase our achievements, and demonstrate the impact of our collective efforts. Alongside exciting scientific updates, I am particularly proud of the work being done to strengthen the platform through initiatives such as our online Equity Diversity Inclusion and Accessibility (EDIA) Hub, which brings together TRIDENT's guiding EDIA principles, Action Plan, governance, and ongoing initiatives in one accessible location, and the launch of the TRIDENT Data
Hub, designed to enhance data sharing, collaboration, and the discoverability of research datasets in support of our open science and reproducibility goals. As you explore this edition of the newsletter, I encourage you to take a moment to celebrate how far we have come together. There is much to be proud of, much to learn from one another, and even more to look forward to as we continue building a more translational, collaborative, and impactful future for
neurotherapeutic research. Warm regards, Ravi
Two New Assays from The Neuro Speed Up the Search for α-Synucleinopathy Therapies
The Neuro's Early Drug Discovery Unit has published two complementary automated assays built on stem-cell-derived dopaminergic neurons. The first, published in Methods, screens for molecules that block cells from absorbing toxic α-Synuclein preformed fibrils. The second, also published in Methods, picks up where the first leaves off, automating the tracking of new α-Synuclein aggregates as they form inside neurons, showing that aggregate formation scales with dose and exposure time and
depends on the neuron's own α-Synuclein levels. Together, the two assays give researchers scalable tools for testing how candidate drugs might interrupt α-Synucleinopathy at different stages, from blocking entry to halting propagation.
Learn more about the TRIDENT iPSC & Organoid Core HERE.
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A New Assay for the Touchscreen Toolkit: Validating Stimulus–Response Learning as an α-Synucleinopathy Biomarker.
Published in Translational Psychiatry, this Mouse Core study adds a validated task to its translational cognitive testing platform. Testing two distinct α-Synuclein fibril strains in the M83 mouse model, the team found that both impaired stimulus–response learning well before motor symptoms emerged, even though only one strain led to overt motor deficits. These findings expand the touchscreen platform’s suite of translational cognitive assays for α-Synucleinopathy research, delivering a robust, cross-species readout to detect cognitive decline in α-Synucleinopathy. Learn more about the TRIDENT Mouse Core HERE.
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It's Not Just Amyloid: Failing Myelin May Be Driving Brain Network Breakdown in Alzheimer's Disease
Posted on bioRxiv, this study from TRIDENT's Mouse Imaging team tracks the default mode network (DMN) in an APP knock-in mouse model as the disease progresses. The team found a biphasic pattern that mirrors what's seen in human Alzheimer's patients: early network hypersynchrony gives way to hyposynchrony as amyloid accumulates, tracking closely with myelin maturation failure and oligodendrocyte precursor loss. Because this same DMN pattern shows up in humans, the findings position myelin-network coupling as a promising candidate for a cross-species imaging biomarker in Alzheimer's disease. Learn more about the TRIDENT
Mouse Core HERE.
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A New Method for Automatic Face-Detection and Tracking of Marmosets in Home Cages
Published in eLife, this study introduces an automated system that identifies individual marmosets in real time using facial recognition and coloured collar beads for tracking freely moving marmosets in home cages. Once trained, it runs on its own, tying behavioural data to the correct individual without an experimenter needing to be present, and is well suited to longitudinal studies like TRIDENT's marmoset research.
Learn more about the TRIDENT Marmoset Core HERE.
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Cognitive Flexibility Falters First in a Preformed Fibrils-Injected Model of Marmosets Posted on bioRxiv, this TRIDENT study is the first to track α-Synuclein pathology, brain structure, functional networks, and cognition together in a single non-human primate cohort over time. Marmosets injected with α-synuclein preformed fibrils showed a selective decline in cognitive flexibility, tied to disruption in fronto-limbic brain networks, while motor or sleep deficits were not seen yet. These findings add non-human primate evidence to a pattern already observed in the Mouse Core's PFF models: cognitive decline precedes overt motor symptoms in α-Synucleinopathy. By mirroring the premotor executive dysfunction documented in prodromal Parkinson’s and Lewy body disease patients, this cross-species convergence reinforces cognitive flexibility as a translationally predictive biomarker.
Learn more about the TRIDENT Marmoset Core HERE.
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The Menopause Blind Spot: What Science Has Been Missing About Brain Health
Published in The British Journal of Psychiatry, this review from TRIDENT’s Sex-Based Analysis + team shows menopause is not one-size-fits-all: its type, along with hormone therapy's formulation, dosing, and route, all shape whether treatment protects the aging brain in women. These are the same kind of sex-based factors TRIDENT accounts for when modelling neurodegenerative disease in preclinical models.
Learn more about the TRIDENT SBA+ Core HERE.
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Sovereignty Through Sharing: TRIDENT Open Science Lead Makes the Case for Open Innovation
Published in Policy Options, this commentary by TRIDENT's Open Science Core lead, Dr. Richard Gold, argues Canada cannot achieve innovation sovereignty alone. He calls for stronger domestic research-industry ecosystems paired with international open science partnerships, the same open, patent-light model TRIDENT itself is built on. Dr. Gold points to leaders like the Montreal Neurological Institute as proof that this approach outpaces isolation, and moves discoveries from bench to bedside faster.
Learn more about the TRIDENT Open Science, Practices and Partnerships Core HERE.
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When Is Large Team Science Collaboration Worth It? TRIDENT Team Science Core Lead Studies What Makes Scientists Say Yes Posted on PhilSci-Archive, this preprint by TRIDENT's Team Science Collaboration lead, Dr. Jackie Sullivan, explores when joining a large team-based research project is worth pursuing. Drawing on interviews with TRIDENT neuroscientists, Dr. Sullivan finds that scientists weigh not just the scientific payoff of collaboration, but the experience they build over time, which shapes how they judge future opportunities to work together. The result is a thoughtful look
at what draws scientists toward large-scale collaboration in the first place.
Learn more about the TRIDENT Open Science, Practices and Partnerships Core HERE.
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The TRIDENT Data Hub, developed by the Data Management and Sharing Team at the Douglas Research Centre CoBrA Lab, serves as a centralized gateway to discover TRIDENT research datasets, metadata, and related resources across the platform. By making research outputs easier to find, access, and reuse, the Data Hub strengthens TRIDENT's commitment to open science while promoting transparency, collaboration, and reproducibility. This
resource supports researchers in locating valuable datasets and encourages greater sharing and validation of scientific findings to accelerate neurotherapeutic discovery. Check out the TRIDENT Data Hub HERE.
New: TRIDENT Equity, Diversity, Inclusion and Accessibility (EDIA) Hub
We’re proud to launch the TRIDENT Equity, Diversity, Inclusion, and Accessibility (EDIA) Hub on our website—a platform-wide resource that reflects our ongoing commitment to fostering a more equitable, diverse, inclusive, and accessible research ecosystem across the national TRIDENT network. The Hub highlights TRIDENT’s EDIA principles, Action Plan, governance structures and platform-wide initiatives, that guide our approach to embedding EDIA across research, training, collaboration, and decision-making. It also showcases the actions we are taking to promote inclusive participation, strengthen accountability, and create meaningful opportunities for researchers, trainees, partners, and communities to contribute to transformative neurotherapeutics research. Check out the TRIDENT EDIA Hub HERE.
Highly Qualified Personnel
HQP Spotlight:
Kruti Joshi
Western Imaging Core
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HQP Spotlight:
Aya Arrar
Western Mouse Core
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HQP Spotlight:
David Roper
Douglas Data Management & Sharing Core
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HQP Spotlight:
Dr. Alessandro Zanini
Western Marmoset Core
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Sriram Jayabal, PhD
TRIDENT Research Program Director Dr. Sriram Jayabal is TRIDENT’s Research Program Director, bringing over a decade of experience in neuroscience. He completed his Bachelor of Technology in Biotechnology in India, then earned his graduate degree at McGill University, where he studied the cerebellar pathophysiology behind spinocerebellar ataxia type 6, a neurodegenerative disease. He spent the next seven years at Stanford University studying the learning rules of the cerebellum, first as a Postdoctoral Fellow and later as a Staff Research Scientist. He has published more than 10 peer-reviewed papers and has trained about 23 students, including undergraduates, graduate students, and research staff. His mentorship was recognized with Stanford's Bio-X Star Mentor Award. At TRIDENT,
Sriram provides scientific leadership and strategic programmatic oversight for a $24M multi-institutional research platform uniting 17 principal investigators across six institutions. He directs progress toward critical translational milestones, ensuring seamless integration of standardized preclinical methodologies and endpoints across the platform's specialized cores. Sriram oversees multi-year programmatic planning, high-stakes funder reporting, and cross-consortium risk mitigation, while building institutional governance frameworks to advance TRIDENT’s mission of systematically de-risking high-potential neurotherapeutics.
Sriram can be reached at sjayaba2@uwo.ca!
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