- Senior Investigator, LCP, NIDDK, NIH, 1994-present
- Member of Technical Staff (Principal Investigator), Physical Chemistry Research Department, AT&T Bell Laboratories, 1986-1994
- Postdoctoral Researcher, University of Pennsylvania, 1984-1986
- Ph.D., University of California at Berkeley, 1984
- A.B., Princeton University, 1980
- Fellow of the American Physical Society (1997), the American Association for the Advancement of Science (2005), the International Society of Magnetic Resonance (2008), and the American Academy of Arts and Sciences (2017)
The purpose of our research is twofold: (1) to expand the capabilities of experimental techniques, especially solid state NMR techniques, for probing structural properties of molecules with central roles in biology and human disease; (2) to provide new structural and mechanistic information about specific biomolecular systems, including protein assemblies that are associated with Alzheimer’s disease, type 2 diabetes, and AIDS.
My lab is currently pursuing several distinct but inter-related projects. We are using solid state NMR and electron microscopy to characterize molecular structures of amyloid-β fibrils, including fibrils that develop in brain tissue of Alzheimer’s disease patients. We are developing new experimental methods that allow detailed molecular structural studies of transient intermediates in processes such as protein folding, ligand binding, peptide aggregation, and protein self-assembly. We are investigating the structural and physical basis for fibril formation by low-complexity protein sequences. We are using solid state NMR to characterize the structures of protein lattices within mature and immature HIV-1 virions. And we are developing ultra-low-temperature methods for sensitivity enhancement in biomolecular solid state NMR and resolution enhancement in magnetic resonance imaging.
- Low-temperature magnetic resonance imaging with 2.8 μm isotropic resolution.
- Chen HY, Tycko R.
- J Magn Reson (2018 Feb) 287:47-55. Abstract/Full Text
- Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes.
- Qiang W, Yau WM, Lu JX, Collinge J, Tycko R.
- Nature (2017 Jan 12) 541:217-221. Abstract/Full Text
Research in Plain Language
We develop new methods for learning the structures of proteins and other molecules that play central roles in human disease. We apply these methods to specific problems where more conventional methods are not adequate. As an example, we developed detailed models of amyloid fibrils that are linked to Alzheimer's disease and type 2 diabetes. Our models reveal the molecular interactions that lead to amyloid formation. This knowledge may inform the design of new chemical compounds to inhibit amyloid formation and for diagnostic imaging.