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Integrative Structural and Computational Biology

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 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. A recent 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. Recently, we have begun to probe mesoscale droplets formed by IDPs with RNA and other partners. These droplets are formed by liquid-liquid phase separation, a process believed to be mechanistically key in the dynamics of membraneless cellular organelles such as the nucleolus.


Watch a lecture (TSRI Faculty Lecture Series) about our work on single-molecule biophysics of protein disorder:
https://www.youtube.com/watch?v=wqdlET1_SQM


Read a recent interview describing some of our lab's emerging research directions:
http://www.news-medical.net/news/20161110/Elucidating-IDP-behaviour-on-crowded-membranes.aspx



Education

Ph.D., (Physical Organic) Chemistry, The University of Chicago, 1996

Selected References


See publication list on pubmed:
https://www.ncbi.nlm.nih.gov/pubmed?term=deniz%20aa

Banerjee PR, Moosa MM, Deniz AA. “Two-Dimensional Crowding Uncovers a Hidden Conformation of α-Synuclein” Angew Chem Int Ed Engl. 2016, 55:12789

Ferreon, A.C.M., Ferreon, J.C., Wright, P.E. & Deniz, A.A.  “Modulation of Allostery by Protein Intrinsic Disorder”.  Nature 2013, 498:390

Banerjee PR, Mitrea DM, Kriwacki RW, Deniz AA. “Asymmetric Modulation of Protein Order-Disorder Transitions by Phosphorylation and Partner Binding.” Angew Chem Int Ed Engl. 2016, 55:1675

Polinkovsky ME, Gambin Y, Banerjee PR, Erickstad MJ, Groisman A, Deniz AA. “Ultrafast cooling reveals microsecond-scale biomolecular dynamics.” Nature Communications 2014, 5:5737

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

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

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

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

Links

Read News-Medical interview on some of our lab’s emerging research directions, including the effects of 2D-crowding on folding of a Parkinson’s disease-linked IDP.

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