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Nath Research Group

Seattle, Washington, US

The Nath Lab is part of the University of Washington's Department of Medicinal Chemistry. We're interested in understanding the roles of protein dynamics in human health and disease. Proteins display a fascinating spectrum of dynamic behavior, ranging from some that are almost static to others that rapidly interconvert between a diverse ensemble of structures. The nature, amplitude and timescales of protein conformational fluctuations can be crucial to biological functions such as enzyme catalysis and intracellular signaling. Mutations, post-translational modifications and environmental factors can perturb protein dynamics – and hence normal function – in ways that are difficult to predict.

We are developing new and powerful methods to characterize and control protein dynamics, building on recent advances in biophysics, biochemistry and pharmacology from groups around the world. Our approaches encompass... Show more »

The Nath Lab is part of the University of Washington's Department of Medicinal Chemistry. We're interested in understanding the roles of protein dynamics in human health and disease. Proteins display a fascinating spectrum of dynamic behavior, ranging from some that are almost static to others that rapidly interconvert between a diverse ensemble of structures. The nature, amplitude and timescales of protein conformational fluctuations can be crucial to biological functions such as enzyme catalysis and intracellular signaling. Mutations, post-translational modifications and environmental factors can perturb protein dynamics – and hence normal function – in ways that are difficult to predict.

We are developing new and powerful methods to characterize and control protein dynamics, building on recent advances in biophysics, biochemistry and pharmacology from groups around the world. Our approaches encompass single-molecule fluorescence and complementary spectroscopic tools, computational modeling, drug design and protein engineering. Initially, we're focusing on proteins involved in degenerative disorders (such as Alzheimer's disease), the oxidative stress response, and drug metabolism.

Recent Publications

  • Booth A, Vane EW, Dovala D, Thorner J. A Förster resonance energy transfer (FRET)-based system provides insight into the ordered assembly of yeast septin hetero-octamers. J Biol Chem. 2015 Sep 28; doi: 10.1074/jbc.M115.683128
  • Nath A, Schlamadinger DE, Rhoades E, Miranker AD. Structure-based small molecule modulation of a pre-amyloid state: pharmacological enhancement of IAPP membrane-binding and toxicity. Biochemistry 2015 Jun 9;54(22):3555-64.
  • Hernando-Pérez M, Lambert S, Nakatani-Webster E, Catalano CE, de Pablo PJ. Cementing proteins provide extra mechanical stabilization to viral cages. Nat Commun. 2014 Jul 29;5:4520.
  • Kumar S, Brown MA, Nath A, Miranker AD. Folded small molecule manipulation of islet amyloid polypeptide. Chem Biol. 2014 Jun 19;21(6):775-81.
  • Munro JB, Nath A, Färber M, Datta SA, Rein A, Rhoades E, Mothes W. A conformational transition observed in single HIV-1 Gag molecules during in vitro assembly of virus-like particles. J Virol. 2014 Mar;88(6):3577-85.
  • Singh P†, Nakatani E†, Goodlett DR, Catalano CE. A pseudo-atomic model for the capsid shell of bacteriophage lambda using chemical cross-linking/mass spectrometry and molecular modeling. J Mol Biol. 2013 Sep 23;425(18):3378-88.
  • Lin Y, Watson KA, Kim JW, Baggett DW, Working DC, Connell JW. Bulk preparation of holey graphene via controlled catalytic oxidation. Nanoscale. 2013 Sep 7;5(17):7814-24.
  • Nath A, Rhoades E. A flash in the pan: dissecting dynamic amyloid intermediates using fluorescence. FEBS Lett. 2013 Apr 17;587(8):1096-105.
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Fluorescence correlation spectroscopy
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Single Molecule Fluorescence Spectroscopy
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Including fluorescence correlation spectroscopy (FCS), brightness analysis, and fluorescence lifetime measurements

Including fluorescence correlation spectroscopy (FCS), brightness analysis, and fluorescence lifetime measurements

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Spectroscopy
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Fluorescence spectroscopy
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