D. Dar, PhD
University of California, San Francisco
Work Phone: 415-734-4941
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 Systems” link
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)
HIV Latency: I am interested in applying a multi-pronged approach of modeling, experimentation, and simulations to understanding the establishment and stability of HIV-1 latency with the 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 fate determination and the phenotypic diversity of various switch-like systems.
Systems Biology and Bioinformatics: A new era in which emerging high throughput technologies flood us with too much data that we don’t know what to do with brings great opportunities. I am interested in the integration of large complex datasets to extract organizational principles of biology, especially across organisms. I also see the 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 current postdoctoral position, 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. We are using this capability to study genome-wide transcriptional regulation of HIV (Dar et al, PNAS 2012).
1. 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. (In press, 2012).
2. 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)
3. 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,” Nature: Mol Sys Biol 28;8:607 (2012)
4. 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).
5. 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).
6. 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).
7. 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) )
8. 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). link
9. 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) link
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).
11. 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).
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.”
"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!"
“Genius is one percent inspiration and 99 percent perspiration.” – Thomas Edison