Speaker: Donald Weaver, Krembil Brain Institute and University of Toronto

Time: Wednesday, January 28, from 2:30 pm to 3:30 pm

Zoom link for online audience: https://wayne-edu.zoom.us/j/92845590121?pwd=CpRA5Wa5gzSMn2xiVkR2abD83O5nrH.1

Title: Applications of In Silico Simulations and Modelling to a Molecular Level Understanding of Alzheimer’s Disease

Abstract: The molecular pathogenesis of Alzheimer’s disease (AD), humankind’s most prevalent dementia, remains unknown; correspondingly, the role of β-amyloid (Aβ) peptide in the cause and progression of AD remains an issue of controversy and dispute. AD research needs an explicit molecular-level understanding of Aβ and the role it plays in AD. We are endeavouring to achieve this understanding through extensive molecular dynamics simulations and other in silico modelling techniques to enable “seeing the unseeable” events that unfold during the molecular mechanistic course of this devastating disease.

          Our in silico simulations have enabled an explicit molecular level understanding of the role of Aβ in the pathogenesis of AD: AD occurs because Aβ is an immunopeptide that cannot differentiate neurons from bacteria – a case of mistaken identity that leads to a self-directed immune attack in which Aβ extracellularly permeates neuronal membranes, while also intracellularly attacking mitochondria. AD thus emerges as a disease of disordered immunity: in response to immune-stimulating events (e.g., infection, trauma, pollution), Aβ is released as an immune peptide with immunomodulatory/antimicrobial duality; however, Aβ's antimicrobial properties result in a misdirected attack upon "self" neurons, arising from the electrotopological similarities between neurons and bacteria in terms of transmembrane potential gradients and anionic charges on outer membrane macromolecules.

          Based upon this comprehensive series of molecular modelling calculations (including molecular dynamics simulations, peptide homology modelling, in silico high throughput screening campaigns) at molecular mechanics and molecular quantum mechanics levels of theory, new insights into the cause of AD have been deduced.

Bio: Donald Weaver initially trained as a neurologist before later pursuing a PhD in computational chemistry with an emphasis on drug design for chronic brain disease. Currently he is Professor of Neurology and Chemistry at the University of Toronto, a Senior Scientist at the Krembil Brain Institute and a neurologist at the Toronto Western Hospital. He has computationally designed two drugs that reached Phase III human clinical trials. He has co-founded multiple start-up biotech companies; his most recent company, Treventis Corp., has recently partnered with Takeda Inc. to develop small molecule therapeutics targeting tau pathology in Alzheimer’s. His academic research is focused on the role of neuroinflammation in dementia.

______________________________________________________________________

CAD Seminar Series: Advancing Knowledge, Innovation, and Collaboration in Computation, AI, and Data Science (CAD)

The CAD Seminar Series is a dedicated platform for advancing knowledge, fostering innovation, and promoting collaboration across the fields of Computation, Artificial Intelligence, and Data Science. This series brings together leading experts, researchers, and professionals to explore the latest developments, tackle emerging challenges, and drive forward-thinking solutions at the convergence of these critical disciplines.

Objectives:

• Advance Knowledge: Share cutting-edge research and insights that push the boundaries of what is known in CAD.

• Foster Innovation: Encourage the development of novel ideas and solutions through interdisciplinary dialogue and creative thinking.

• Promote Collaboration: Unite expertise across disciplines and build bridges between academia, industry, and government to address complex problems and create opportunities for joint ventures.

Target Audience: The CAD Seminar Series is designed for a diverse audience, including faculty, researchers, students, and professionals in Computation, AI, Data Science, and related fields. It serves as a forum for exchanging ideas, networking, and contributing to the growth of these rapidly evolving areas. We highly recommend in-person attendance to enhance engagement and networking opportunities with speakers and fellow participants.

Call for Participation: We welcome contributions from researchers, practitioners, and students. Whether presenting your work, participating in discussions, or attending as a learner, your involvement is crucial to the success of this collaborative initiative.