Roy D. Dar

Postdoctoral Fellow

Gladstone Institute for Virology and Immunology &

Center for Systems and Synthetic Biology

University of California, San Francisco

Work Phone: 415-734-4941
Email:
roy.dar@gladstone.ucsf.edu

My Brief History of Time

July 2011 – present  Postdoctoral Fellow, Gladstone Institutes, University of California, San Francisco (UCSF)

I'm currently a postdoctoral fellow with research interests at the cross-section of virology, biophysics, and systems biology (see research interests below).

2006 – 2011 Graduate Research Assistant in the “Emergent Properties” theme at the Oak Ridge National Laboratory (ORNL) Center for Nanophase Materials Sciences under the direction of Dr. Michael Simpson.

Topic: Organizational principles of complex genetic systems. PhD earned from UTK.

 

Dissertation: “Adaptation and Stochasticity of Natural Complex Systemslink

 

Jan-Sept 2005           Science Undergraduate Laboratory Internship through the DOE-Office of Science with the Molecular-Scale Engineering and Nanoscale Technologies (MENT) Research Group at (ORNL).

Topic: Experimentation and Modeling of Stochastic Processes in Bacterial Cells.

 

May-August 2004     Student Research Assistant in Prof. Dan Davidov’s Experimental Condensed Matter Group, Hebrew University of Jerusalem, Israel (HUJI).

Topic: Scanning ferromagnetic resonance microscopy and resonant heating of magnetite nanoparticles (with F. Sakran, Ph.D.)

 

2001- 2004   B.Sc. Physics and Mathematics, Hebrew University of Jerusalem, Israel (HUJI)

 

 

Research Interests

HIV-1 Latency: I am interested in applying a multi-pronged approach of modeling, experimentation, and simulations to control regulation and stability of the latent HIV reservoir with an ultimate goal of guiding strategic drug therapies.

Noise Biology: My interests lay in the potential of gene expression fluctuations as a gene circuit discovery tool. These studies have two components – (1) Using noise as a probe to elucidate underlying structure-function relationships of the genetic circuitry, and (2) Understanding the implications of the noise in cell-fate determination and the phenotypic diversity caused by various switch-like systems.

Systems Biology and Bioinformatics: A new era in which emerging high throughput technologies flood us with more data than we know what to do with brings great opportunities. I am interested in the integration of large complex datasets to extract organizational principles of biology. I also appreciate potential at the interface of machine-learning and systems biology and am interested in new and exciting projects that combine the two.

Keywords: Stochastic gene expression, structure-function relationships of genetic circuits, single cell measurements, transcriptional plasticity, gene regulatory networks, HIV-1 regulation and decision making

 

Research in brief

My research interests have focused on the fields of biophysics and systems biology. I began my quantitative scientific training with the modeling and experimentation of genetic circuits in an internship with Michael Simpson at ORNL/UTK. My PhD laboratory developed a frequency-domain analysis of gene-expression fluctuations. My doctoral research helped demonstrate that negative autoregulatory motifs high-pass filter gene-expression noise in E. coli (Austin et al, Nature 2006). Later studies demonstrated that HIV-1 positive autoregulation is sufficient for a transient fate determination of the virus (Weinberger*, Dar* & Simpson, Nature Genetics 2008, *Equal contribution). In my postdoctoral fellowship I have expanded the application of modeling gene-circuit dynamics and time-series single-cell data on a genome-wide level by using lentiviral vectors to integrate gene circuits of interest across the genome. This capability enabled the investigation of genome-wide transcriptional regulation of HIV and housekeeping promoters (Dar et al, PNAS 2012). This was followed by developing and performing the first noise drug screen which detected a new class of noise modulating compounds for enhanced control of HIV latency (Dar et al, Science 2014).

 

Publications

1.     R. D. Dar, N. N. Hosmane, M. R. Arkin, R. F. Siliciano, L. S. Weinberger, “Screening for noise in gene expression identifies drug synergies,” Science, DOI:10.1126/science.1250220 (Jun 5, 2014).

2.     D. Boehm, V. Calvanese, R. D. Dar, S. Xing, S. Schroeder, L. Martins, K. Aull, P. Li, V. Planelles, J. E. Bradner, M. Zhou, R. F. Siliciano, L. S. Weinberger, E. Verdin, M. Ott. “BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism”. Cell Cycle (2012).

3.     M. W. Teng, C. Bolovan-Fritts, R. D. Dar, A. Womack, T. Shenk, M. L. Simpson, and L. S. Weinberger. An Endogenous Accelerator for Viral Gene Expression Provides a Fitness Advantage,” Cell 151, 1569 (Dec 21, 2012).

4.     R. D. Dar*, B. S. Razooky*, A. Singh, T. V. Trimeloni, J. M. McCollum, C. D. Cox, M. L. Simpson, and L. S. Weinberger, “Transcriptional burst frequency and burst size are equally modulated across the human genome,” Proc. Nat. Acad. Sci. USA 109(43):17454-9 (2012) (* -- Equal contribution).

ą Featured in review by Sanchez and Golding, Science (2013).

5.     A. Singh, B. S. Razooky, R. D. Dar, and L. S. Weinberger. “Dynamics of protein noise can distinguish between alternative sources of gene-expression variability,” Mol. Syst. Biol. 28;8:607 (2012)

6.     D. K. Karig, P. Siuti, R. D. Dar, S. T. Retterer, M. J. Doktycz, and M. L. Simpson. “Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance,” Nano Comm. Net. 2:39-49 (2011).

7.     R. D. Dar, D. K. Karig, J. F. Cooke, C. D. Cox, and M. L. Simpson, “Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae,” Chaos 20, 037106 (2010).

8.     M. L. Simpson, C. D. Cox, M. S. Allen, J. M. McCollum, R. D. Dar, D. K. Karig, and J. F. Cooke, “Noise in Biological Circuits,” John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 1 214-225 (2009).

9.     L. S. Weinberger*, R. D. Dar*, & M. L. Simpson, “Transient-mediated fate determination in a transcriptional circuit of HIV,” Nature Genetics 40, 466 - 470 (2008), (* -- Equal Contribution).

(See news and views Highlight: Nachman and Ramanathan, Nature Genetics 40, 382 - 383 (2008) )

10. C. D. Cox, J. M. McCollum, M. S. Allen, R. D. Dar, and M. L. Simpson, “Using noise to probe and characterize gene circuits,” Proc. Nat. Acad. Sci. USA, 105(31), 10809-10814. (2008).

11. D. W. Austin, M. S. Allen, J. M. McCollum, R. D. Dar, J. R. Wilgus, G. S. Sayler, N. F. Samatova, C. D. Cox, and M. L. Simpson, "Gene Network Shaping of Inherent Noise Spectra," Nature 439, 608-611 (2006). (Invited Review Chapter)

12. C. D. Cox, J. M. McCollum, D. W. Austin, M. S. Allen, R. D. Dar, and M. L. Simpson, “Frequency domain analysis of noise in simple gene circuits,” Chaos 16, 026102 (2006).

13. C. D. Cox, J. M. McCollum, D. W. Austin, R. D. Dar, M. S. Allen, N. F. Samatova, and M. L. Simpson, “Estimation of spectral properties and kinetic parameters from stochastic measurements of reporter gene activity in single cells,” 2005 Foundations of Systems Biology in Engineering; Santa Barbara, CA.357-360 (2005).

 

 

Quotes

Those interested in Biological Noise may appreciate this one (perhaps biology and cells have been listening to Mel Brooks!):

 

“Look, I really don't want to wax philosophic, but I will say that if you're alive, you got to flap your arms and legs, you got to jump around a lot, you got to make a lot of noise, because life is the very opposite of death. And therefore, as I see it, if you're quiet, you're not living. You've got to be noisy, or at least your thoughts should be noisy and colorful and lively.”

-Mel Brooks

 

"You ask me if an ordinary person could ever get to be able to imagine these things like I imagine them. Of course! I was an ordinary person who studied hard. There are no miracle people. It happens they get interested in this thing and they learn all this stuff, but they're just people. There's no talent, no special ability to understand quantum mechanics, or to imagine electromagnetic fields, that comes without practice and reading and learning and study. I was not born understanding quantum mechanics -- I still don't understand quantum mechanics! I was born not knowing things were made out of atoms, and not being able to visualize, therefore, when I saw the bottle of milk that I was sucking, that it was a dynamic bunch of balls bouncing around. I had to learn that just like anybody else. So if you take an ordinary person who is willing to devote a great deal of time and work and thinking and mathematics, then he's become a scientist!"

 

-Richard Feynman

 

 “Genius is one percent inspiration and 99 percent perspiration.” – Thomas Edison