EPFL BioE Talks SERIES "Mechanistic Data From Ultrafast 2D Infrared Spectroscopy Leads to an Atomic Structural Model of an Amyloid Oligomer"
Event details
| Date | 05.05.2025 |
| Hour | 12:15 › 13:15 |
| Speaker | Prof. Martin T. Zanni, University of Wisconsin, Madison, WI (USA) |
| Location | Online |
| Category | Conferences - Seminars |
| Event Language | English |
WEEKLY EPFL BIOE TALKS SERIES (sandwiches provided)
Abstract:
Obtaining the atomic structures of amyloid oligomers is one of the biggest outstanding problems in structural biology. Amyloid oligomers are transient species, often present at low concentrations. As such, they are not easily amenable to traditional structural biology techniques like X-ray crystallography, NMR spectroscopy or cryoEM microscopy. If aggregation can be slowed or the oligomers trapped by either stabilizing the oligomer or destabilizing the fibrils, then atomic structures have been determined, but only in a few rare cases and under conditions that may be perturbative to the natural structure. In this talk, 2D IR spectroscopy of the human islet amyloid polypeptide (hIAPP) associated with type 2 diabetes will be presented. Mechanistic information on the aggregation mechanism has been obtained by monitoring the kinetics from monomers to oligomers to fibrils. Using isotope labeling, a quaternary fold of the oligomer has been discovered in an important region of the protein. With that information, alongside homologous sequences between species, a few mutations were placed that extended aggregation time from hours to days. That enables high-resolution 2D/3D NMR spectroscopy for the first time on hIAPP, giving rise to more than 300 structural constraints. Replica exchange molecular dynamics generated a structure that satisfies both the 2D IR and NMR constraints, providing the first oligomer model for hIAPP. It has implications for drug discovery and the effects of a familial mutation that leads to early onset type 2 diabetes.
Bio:
Martin T. Zanni is the Meloche-Bascom Professor of Chemistry at the University of Wisconsin-Madison. He received his PhD from the University of California-Berkeley, working with Dan Neumark, and was an NIH Postdoctoral Fellow at the University of Pennsylvania with Robin Hochstrasser. He is one of the early pioneers of 2D IR spectroscopy and has made many technological innovations that have broadened the capabilities and scope of multidimensional spectroscopies and microscopies. He utilizes these new techniques to study topics in biophysics, chemical physics, photovoltaics, and surfaces. He has received many national and international accolades for his research. Notably, he is the only person to have received the ACS Nobel Laureate Signature Award as both a student and a mentor and the first person to receive the Craver, Coblentz, and Lippincott Awards. He founded PhaseTech Spectroscopy Inc., which is the first company to commercialize 2D IR and 2D Electronic spectroscopies.
Zoom link (with one-time registration for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks
Instructions for 1st-year Ph.D. students who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
Abstract:
Obtaining the atomic structures of amyloid oligomers is one of the biggest outstanding problems in structural biology. Amyloid oligomers are transient species, often present at low concentrations. As such, they are not easily amenable to traditional structural biology techniques like X-ray crystallography, NMR spectroscopy or cryoEM microscopy. If aggregation can be slowed or the oligomers trapped by either stabilizing the oligomer or destabilizing the fibrils, then atomic structures have been determined, but only in a few rare cases and under conditions that may be perturbative to the natural structure. In this talk, 2D IR spectroscopy of the human islet amyloid polypeptide (hIAPP) associated with type 2 diabetes will be presented. Mechanistic information on the aggregation mechanism has been obtained by monitoring the kinetics from monomers to oligomers to fibrils. Using isotope labeling, a quaternary fold of the oligomer has been discovered in an important region of the protein. With that information, alongside homologous sequences between species, a few mutations were placed that extended aggregation time from hours to days. That enables high-resolution 2D/3D NMR spectroscopy for the first time on hIAPP, giving rise to more than 300 structural constraints. Replica exchange molecular dynamics generated a structure that satisfies both the 2D IR and NMR constraints, providing the first oligomer model for hIAPP. It has implications for drug discovery and the effects of a familial mutation that leads to early onset type 2 diabetes.
Bio:
Martin T. Zanni is the Meloche-Bascom Professor of Chemistry at the University of Wisconsin-Madison. He received his PhD from the University of California-Berkeley, working with Dan Neumark, and was an NIH Postdoctoral Fellow at the University of Pennsylvania with Robin Hochstrasser. He is one of the early pioneers of 2D IR spectroscopy and has made many technological innovations that have broadened the capabilities and scope of multidimensional spectroscopies and microscopies. He utilizes these new techniques to study topics in biophysics, chemical physics, photovoltaics, and surfaces. He has received many national and international accolades for his research. Notably, he is the only person to have received the ACS Nobel Laureate Signature Award as both a student and a mentor and the first person to receive the Craver, Coblentz, and Lippincott Awards. He founded PhaseTech Spectroscopy Inc., which is the first company to commercialize 2D IR and 2D Electronic spectroscopies.
Zoom link (with one-time registration for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks
Instructions for 1st-year Ph.D. students who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
- send D. Reinhard a note well ahead of time (ideally before seminar day), informing that you plan to attend the talk online, and, during seminar:
- be signed in on Zoom with a recognizable user name (not any alias making it difficult or impossible to identify you).
Practical information
- Informed public
- Registration required
Organizer
- Prof. Sylvie Roke, Institute of Bioengineering
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD