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Ashok Deniz, Ph.D.

Associate Professor
Department of Integrative Structural and Computational Biology
California Campus
Laboratory Website
deniz@scripps.edu
(858) 784-9192

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Single-Molecule Biophysics
       We develop and use single-molecule fluorescence methods to address a number of key issues in molecular and cell biology. These novel single-molecule methods provide unprecedented abilities for investigating the structural distributions and dynamics of complex systems. For example, we are able to directly observe multiple species, steps, pathways and complex kinetics in protein folding and misfolding. Among the many advantages of such an approach is that this data allows us to conduct direct tests of biological models and theories. Additionally, we develop methods to visualize and understand the steps involved in the assembly and function of complex structures such as the RNAi machinery that carry out numerous important functions in cells. Our work utilizes a synergistic array of tools from Chemistry, Physics, Chemical Biology and Biology.
       A particular focus in our current research efforts is the investigation of Intrinsically Disordered Proteins (IDPs). In contrast with a common view of most proteins as having a well-defined 3-dimensional structure that encodes their functions in the cell, IDPs have long stretches of sequence relatively devoid of structure. These protein systems are very prevalent in genomes, especially in more evolved organisms, and the physics of these systems is believed to play a key role in many cellular functions including signaling, scaffolding, gating and timing. Additionally, misfunction in such proteins is linked with diseases such as Parkinson’s and Alzheimer’s diseases. Our recent studies on a couple of representative IDPs have intriguingly revealed that these IDPs can be rather compact and yet rapidly flicker between different structures, and that binding of apparently simple partners can result in folding into multiple shapes on complex and tunable energy landscapes.

Education

B.S., University of Bombay, 1988
M.S., Indian Institute of Technology, Bombay, 1990
Ph.D., (Physical Organic) Chemistry, The University of Chicago, 1996

Professional Experience

Awards & Professional Activities

Selected References

Ferreon, A.C.M., Ferreon, J.C., Wright, P.E. & Deniz, A.A.  “Modulation of Allostery by Protein Intrinsic Disorder”.  Nature 2013, 498:390
See Nature News and Views, Chemical and Engineering News, Cell (Leading Edge Select)Faculty of 1000

Gambin, Y., VanDelinder, V., Ferreon, A.C.M., Lemke, E.L., Groisman, A. & Deniz, A.A.  “Visualizing a one-way protein encounter complex by ultrafast single-molecule mixing”. Nature Methods, 2011, 8:239
See TSRI Press Release
, Nature Methods News and Views, Faculty of 1000, Physics Today Highlight

Mukhopadhyay, S., Krishnan, R., Lemke, E.L., Lindquist, S., Deniz, A.A.  “A natively unfolded yeast prion monomer adopts an ensemble of compact and fluctuating structures”. Proc. Natl. Acad. Sci. USA, 2007, 104: 2649
See TSRI Press Release

Ferreon, A.C.M., Moran, C.M., Ferreon, J.C., Deniz A.A. “Alteration of the α-synuclein Folding Landscape by a Mutation Related to Parkinson’s Disease”  Angew. Chem. Int. Ed. Eng., 2010, 3469
Listed by Angew. Chem. as a "Very Important Paper"

Gambin, Y., Schug, A., Lemke, E.A., Lavinder, J.J., Ferreon, A.C.M., Magliery, T.J., Onuchic, J.N., Deniz, A.A.  “Direct single-molecule observation of a protein living in two opposed native structures” Proc. Natl. Acad. Sci. U.S.A., 2009, 106: 10153
TSRI Press Release
"Must Read" paper on Faculty of 1000 Biology website

Deniz, A.A., Mukhopadhyay, S., Lemke, E.L. “Single-molecule biophysics: at the interface of biology, physics and chemistry” J. Royal Soc. Interface, 2008, 5(18):15-45
Among "Most Read" papers on the JRSI website

Gambin, Y., Deniz, A.A. “Multicolor single-molecule FRET to explore protein folding and binding” Molecular BioSystems, 2010, 6:1540
In special Issue on Emerging Investigators at Chemical and Systems Biology Interfaces

Berezhna, S.Y., Supekova, L., Supek, F., Schultz, P.G., Deniz, A.A. “siRNA in human cells selectively localizes to target RNA sites”  Proc. Natl. Acad. Sci., USA, 2006, 103: 7682-7687
"Must Read" paper on Faculty of 1000 Biology website

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

Scientists Develop Method to Identify Fleetingly Ordered Structures from Intrinsically Disordered Protein