Source: Interfolio F180
Ashok Deniz, PhD
Research Focus
Our research is broadly focused around deriving fundamental physical rules governing the properties of complex protein, RNA and other biopolymers at a range of spatial and time scales, with deep implications for biology and disease. We study these fascinating molecular species and tunable materials they can assemble into, and also develop state-of-the-art single-molecule and other biophysical tools for this purpose.
One research focus is on Intrinsically Disordered Proteins (IDPs). While many proteins have well-defined 3-dimensional structures, IDPs have stretches of flexible sequence. IDPs are prevalent in proteomes, and their physics can play key roles in many cellular functions. Our single-molecule studies have shed light on the tunable nature of IDP structural landscapes, with implications for function and diseases such as Parkinson's and Alzheimer's diseases.
We also have a strong interest in understanding the basic biophysics of larger structures that RNA and proteins can assemble into in cells, specifically dynamic structures known as condensates or membraneless organelles. Such structures (well known examples are the nucleolus and stress granules) can have a range of material properties (liquid-like, viscoelastic, solid) as well as complex structural features that are believed to be mechanistically key in the dynamics and functions in cells.
We also develop and use single-molecule fluorescence methods to address key issues in molecular and cell biology. Single-molecule methods provide unprecedented views of structural and dynamic complexity in proteins and other biological macromolecules, allowing us to directly test biological models and theories.
Links
Scientists "Watch" as Individual Alpha-Synuclein Proteins Change Shape
Researchers Observe Single Protein Dimers Wavering Between Two Symmetrically Opposed Structures
Scripps Research Study Reveals Structural Dynamics of Single Prion Molecules
Education
Ph.D. ((Physical Organic) Chemistry), The University of Chicago, 1996M.S. (Chemistry), University of Chicago, 1994
M.S. (Chemistry), Indian Institute of Technology, 1990
B.S. (Chemistry), St.Xavier's College (University of Bombay), 1988
Professional Experience
2000-2007 Assistant Professor, Scripps Research2007-2021 Associate Professor, Scripps Research
2021-Present Professor, Scripps Researchw
Awards & Professional Activities
2016 TSRI Outstanding Mentor Award1985 Meenal Dinkar Rao Mugve Scholarship, Chemistry, St. Xavier's College
1985 Rustomjee Byramjee Jeejeebhoy Colgen Jubilee Prize, Physics, St. Xavier's College
Selected Publications
Banerjee, P. R.; Moosa, Mahdi M.; Deniz, Ashok A. Two-dimensional crowding uncovers a hidden conformation of a-synuclein. Angewandte Chemie-International Edition 2016, 55, 12789-12792.
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Ferreon, A. C.; Ferreon, J. C.; Wright, Peter E.; Deniz, Ashok A. Modulation of allostery by protein intrinsic disorder. Nature 2013, 498, 390-394.
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Banerjee, Priya R.; Mitrea, Diana M.; Kriwacki, Richard W.; Deniz, Ashok A. Asymmetric Modulation of Protein Order-Disorder Transitions by Phosphorylation and Partner Binding. Angewandte Chemie 2015, 55, 1675-1679.
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Polinkovsky, M. E.; Gambin, Y.; Banerjee, P. R.; Erickstad, M. J.; Groisman, A.; Deniz, Ashok A. Ultrafast cooling reveals microsecond-scale biomolecular dynamics. Nature Communications 2014, 5, 5737.
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Gambin, Y.; VanDelinder, V.; Ferreon, A. C.; Lemke, E. A.; Groisman, A.; Deniz, Ashok A. Visualizing a one-way protein encounter complex by ultrafast single-molecule mixing. Nature Methods 2011, 8, 239-241.
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Mukhopadhyay, S.; Krishnan, R.; Lemke, E. A.; Lindquist, S.; Deniz, Ashok A. A natively unfolded yeast prion monomer adopts an ensemble of collapsed and rapidly fluctuating structures. Proceedings of the National Academy of Sciences of the United States of America 2007, 104, 2649-2654.
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