Laboratory of Quantitative Biology

Terry Hwa, Principal Investigator

research supported by

               

Areas of Research   

Current activities in our lab are in the area of quantitative and systemic biology. This is an emerging area of research at the interface of biology,  biochemistry, engineering, and physics. In this post-genome era,  it is clear that the complexity of a biological organism resides not merely in the intricacies of its components (e.g., proteins), but more importantly in the array of interactions these components can have with each other.  This shift of paradigm is initiating a revolution in biology: Instead of focusing on genes, proteins, and pathways, bioloigsts are beginning to think in terms of modules and networks. However, a significant challenge lies in the fact that much of the interactions of the subsystems are yet unknown.

Our research is focused on microbiology, particularly on the bacterium E. coli which is the best characterized living organism both molecularly and physiologically. In the long run, we wish to develop a comprehensive understanding of the organism, i.e., understanding its physiological response under various growth conditions in molecular terms. However even for E. coli, a global approach seems premature in our opinion due to the many missing molecular players and interactions. Thus, we work on smaller sub-systems, with the insistence on developing quantitative links from molecules all the way to cell physiology. Our emphasis can be regarded as the "vertical approach", which complements the "horizontal approach" favored by the 'omics technology. An introduction to our vertical, quantitative approach is described in a recent course on quantitative molecular biology developed by our laboratory.

Vertical integration requires a command of the vast knowledge accumulated over many decades of research in molecular and microbiology, as well as a combination of experimental and theoretical efforts. Some of the experiments are being carried out in our own lab; others are done together with biology collaborators. Our experiments are often theory-motivated, yet discoveries made in the lab has inspired fresh theoretical view points. In similar ways, our theoretical studies play the dual role of analyzing experimetal results and guiding new generation of experiments. The close interaction between theory and experiment allows the theorists to be in contact with biological reality, and allows the experimentalists to have a good sense of the power (and limitations) of quantitative analysis. In this way, we hope to train a new generation of scientists who can freely exploit opportunities at the interface between biology and physics.

Below are some topics our lab has been working in recent years; all projects involve experimental and theoretical  components.

• gene regulation: quantitative characterization of combinatorial transcriptional control; de novo synthesis of novel transcriptional control; quantitative characterization of post-transriptional control by regulatory small RNA;
  
  
• protein-protein interaction: specificity and cross-talk in two-component signaling; assembly of macromolecular complexes;
  
  
• molecular evolution: directed evolution of promoters, cis-regulatory sequences, and signaling molecules; analysis of evolved seqeunces to deduce rules of molecular interaction;
  
  
• genetic circuits: quantitative characterization of various endogenous genetic circuits; synthesis and characterization of artificial circuits;
  
  
• metabolic control: interaction and coordination of metabolic pathways; systems being studied include carbon/nitrogen metabolism, aerobic/anarobic control, Fe/oxidative stress;
  
  
• physiology & cell growth: coordination of growth and metabolic activities; control of ribosome synthesis and cell growth; control of cell division;                                                
  

Personnel & Affiliations

Current and affiliated lab members:

    Conghui You, post-doc (2008 -- )
    Xin Liu, exchange student (2008 -- )
    Alex Beath, post-doc (2008 -- )
    Carmen Situ, undergrad biochem (2007 -- )
    Tony Hui, grad student (2007 -- )
    Dalai Yan, project scientist (2007 -- )
    David Erickson, grad student (2007 -- )
    Barret Deris, grad student (2007 -- )
    Po-han Lee, visiting scientist (2007 -- )
    Stefan Klumpp, post-doc (2006 -- )
    Matt Scott, post-doc (2006 -- )
    Peter McHale, post-doc (2005 -- )
    Erel Levine, post-doc (2005 -- )
    Robert White, post-doc (2004 -- )
    Zhongge Zhang, project scientist (2003)

Short-term visitors:

    Patrick Levi, Erlangen (2008)
    Martin Weigt, ISI Torino (2008)
    Vladimir Teif, Minsk (2008)
    Peter Lenz, Marburg (2007, 2008)

Former lab members:

    Albert Tsai, undergrad biophysics (2006 -- 2007)
    Robert Yee, undergrad biology (2005 -- 2007)
    Jian Liu, post-doc (2005 -- 2007)
    Eddy Mateescu, post-doc (2005 -- 2007)
    Tom Kuhlman, Ph.D. student (2003 -- 2007)
    Sabrina Li, MS student (2004 -- 2007)
    Shumo Liu, specialist (2003 -- 2006)
    Weiqun Peng, post-doc (2001 -- 2004)
    Rolf Olsen, Ph.D. student (1998 -- 2003)
    Nicolas Buchler, post-doc (2001 -- 2003)
    Ulrich Gerland, post-doc (2000 -- 2003)
    Peter Arndt, post-doc (2001 -- 2003)
    Roman Sasik, post-doc (1999 -- 2001)
    David J. Moroz, post-doc (1998 -- 2001)
    Ralf Bundschuh, post-doc (1997 -- 2001)
    Dinko Cule, post-doc (1995 -- 1997)
    Jan Kierfeld, exchange Ph.D. student (1995 - 1996)

Positions available

   expt post-docs: immediate opening for candidates with experience in microbiology and/or biochemistry;
                           interest in quantitative studies is preferred but not necessary;

   theory post-docs: candidates should apply through CTBP

   grad students:  immediate openings in experiment biology; experience is not necessary but passion is required.

Resources:

Biology collaborators:

    Ethan Bier lab, Developmental Biology, UCSD
    Lin Chao lab, Evolutionary Biology, UCSD
    Antoine Danchin lab, Pasteur Institute
    Jeff Hasty lab, Bioengineering, UCSD
    Jim Hoch lab, Molecular and Cellular Biology, Scripps
    Sydney Kustu lab, Microbiology, Berkeley
    Bill Loomis lab, Developmental Biology, UCSD
    Bill McGinnis lab, Developmental Biology, UCSD
    Dmitri Petrov lab, Evolutionary Biology, Stanford
    Milton Saier lab, Molecular Biology, UCSD
    Yiping Wang lab, Peking Univ, China

Local organizations:

    Center for Theoretical Biophysics
    Molecular Biophysics training program
    Bioinformatics training program
    Department of Physics
    Division of Biological Sciences
    Department of Bioengineering
    Department of Chemistry and Biochemistry
    The Scripps Research Institute
    Salk Institute
    San Diego Microbiology Group

(p)reprints/seminars/conferences:
    q-bio archive
    pubmed
    bio-related local seminars

Contact Information

    Campus directory

    Campus map