Structure Determination of Amyloid Fibrils by Cryo-EM
Gunnar Schroeder
Heinrich-Heine University Düsseldorf
Friday, March 28, 12:00 PM, C215 ESC
Abstract:
A variety of mouse models are used in Alzheimer's disease (AD) research. However, little is known about the structural differences in aggregated Aβ between mouse models and humans or in vitro structures. These differences might help to understand why fibril-targeting drug candidates show efficacy when tested in mouse models but often fail to show the desired effect in clinical trials. We determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy (cryo-EM). We found that these fibril structures are different from the most dominant structures found in AD patients. A detailed assessment of the Aβ fibril structure is therefore important to the selection of appropriate mouse models for the preclinical development of novel plaque-targeting therapeutics in AD. In addition to protein deposits, such as plaques in AD and Lewy bodies in α-synucleinopathies like Parkinson’s disease (PD), a high concentration of lipids is also found, suggesting a potential role for lipids in disease progression. We present cryo-EM studies of Aβ40 and α-synuclein fibrils formed in the presence of liposomes. These structures provide detailed insights into fibril-lipid interactions and show that the fibrils can take up substantial amounts of lipids during formation, which results in lipid-decorated fibrils. This supports the notion that lipid extraction from cell membranes may be a mechanism contributing to fibril toxicity. Understanding these fibril-lipid interactions offers structural insights into disease-relevant processes in AD and PD.
Biographical Sketch:
Professor Schroeder works on both the application of cryo-EM for biomolecular structure determination and also the development of computational tools for cryo-EM. His focus is to determine of structures of amyloid fibrils in collaboration with colleagues at the ICS-6 in Jülich and the IPB in Düsseldorf. Amyloid fibrils play a significant role in many neurodegenerative diseases, such as Alzheimers or Parkinsons disease.
Nuclear Reactor Physics and The Neo-Renaissance of Nuclear Energy
Taylor Kimball
University of Utah
Friday, April 11, 12:00 PM, C215 ESC
Abstract:
Nuclear energy is facing a "Neo-Renaissance," with increased interest and demand worldwide in utilizing nuclear powerplants for electricity production. For the first time in recent years, electricity demand around the globe is set to surge due to artificial intelligence power requirements, increasing number of data centers, and manufacturing growth. Due to the low carbon emissions and high reliability of nuclear power, private companies and countries around the world are turning to nuclear power to satisfty the increased electricity demand. In this talk, I will briefly summarize the fundamental principles of nuclear reactor analysis and reactor physics, including important nuclear processes, neutron cross sections, and the neutron transport equation. I will discuss both the stochastic (Monte Carlo) and deterministic (discrete ordinates) computational methods used to solve the neutron transport equation while highlighting several research projects completed during my PhD research. Finally, I will discuss the need and opportunity for physics students to contribute to the rapidly evolving nuclear engineering field
Biographical Sketch:
Taylor Kimball is currently a nuclear engineering Ph.D. student at the University of Utah with an emphasis on computational methods applied to reactor physics. After graduating in May, he is planning to work for the Air Force Technical Applications Center. Taylor received a B.S in physics from BYU in 2022 and an M.S. Nuclear Engineering from the U of U in 2024
Deep (machine) learning
Pratik Chaudhari
University of Pennsylvania
Wednesday, September 17, 12:00 PM, C215 ESC
Abstract:
Biographical Sketch:
Dr.Chaudhari is an Assistant Professor in the Electrical and Systems Engineering department and a core faculty in the General Robotics, Automation, Sensing and Perception (GRASP) Laboratory. He holds a secondary appointment in the Computer and Information Sciences department and is a member of the Applied Mathematics (AMCS) graduate group, Penn Institute for Computational Science (PICS), Center for AI-enabled Systems: Safe, Explainable, and Trustworthy (ASSET) and Center For AI And Data Science For Integrated Diagnostics (AI2D).
Previously, he held a joint position as a Senior Applied Scientist at Amazon Web Services and was a post-doctoral researcher at the California Institute of Technology in Computing and Mathematical Sciences.
He defended his PhD thesis in the Computer Science department at University of California, Los Angeles in 2018 where he worked with Stefano Soatto in the UCLA Vision Lab. He has Engineer's (2014) and Master's (2012) degrees in Aeronautics & Astronautics from the Massachusetts Institute of Technology where he worked with Emilio Frazzoli at the Laboratory of Information and Decision Systems (LIDS). He was in the Aerospace Engineering department at IIT Bombay for his undergraduate studies until 2010.
He has worked extensively on self-driving cars in the areas of motion planning and computer vision at nuTonomy Inc (now Hyundai-Aptiv Motional).
We welcome anyone who wish to attend, and typically serve refreshments ten minutes before the colloquium begins. Speakers generally keep their presentation accessible to undergraduate physics students.