Cats but not Rats? Hominids but not Hamsters? A Study into the Molecular Mechanism of Type 2 Diabetes Using 2D IR Spectroscopy

Martin T. Zanni is the Meloche-Bascom Professor of Chemistry at the University of Wisconsin-Madison. 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. He utilizes these new techniques to study topics in biophysics, chemical physics, photovoltaics, and surface science. He has received many national and international accolades for his research, including the Research Initiatives Award from the National Academy of Sciences for his work in optics, the Raymond and Beverly Sackler Prize from Tel Aviv University for his work in multidimensional spectroscopy, and the Early Career Scholar Award from the NIH/NIDDK for his work on Type 2 diabetes. He is the only person to have received the ACS Nobel Laureate Signature Award as both a student and a mentor. And, most recently, he is the first person to receive both the Craver and the Coblentz Awards. He founded PhaseTech Spectroscopy Inc., which is the first company to commercialize 2D IR and 2D Visible spectroscopies.

Aggregation of the human islet amyloid polypeptide (hIAPP or amylin) is a probable cause of insulin loss in type 2 diabetes.  Using 2D IR spectroscopy and isotope labeling, we have discovered an intermediate in the aggregation pathway in which the central sequence of hIAPP forms parallel beta-sheets before rearranging into the disorder loop of the amyloid fibers.  This structural rearrangement creates a free energy barrier that stabilizes the toxic oligomers. Our discovery helps rationalize a wide range of previous fragment and mutation studies that links the aggregation to type 2 diabetes across a wide range of species. 

Serrano, Arnaldo; Lomont, Justin; Tu, Ling-Hsien; Raleigh, Daniel; Zanni, Martin, "A Free Energy Barrier Caused by the Refolding of an Oligomeric Intermediate Controls the Lag Time of Amyloid Formation by hIAPP", JACS, 139, 16748 (2017)

Petti, Megan; Lomont, Justin; Maj, Michał; Zanni, Martin, “2D Spectroscopy is Being Used to Address Core Scientific Questions in Biology and Materials Science", J. Phys. Chem. B, 2018, 122, 1771. DOI: 10.1021/acs.jpcb.7b11370

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