Gábor Balázsi, Ph.D. 2001, University of Missouri The University of Texas M. D. Anderson Cancer Center Department of Systems Biology Contact Information

Research Interests:

• Mathematical/computational modeling and experimental characterization of biomolecular interaction networks
• Molecular mechanisms underlying cellular defense and cell population survival in stress conditions

Project #1. We study by experiment and computational modeling the combined effect of noise and feedback regulation on the development of drug resistance. Our earlier studies proved that noise can aid survival after a single exposure to stress. The current project will test the effect of feedback regulation on the development and maintenance of non-genetic drug resistance. We will apply multiple exposures to stress, testing how a cell population benefits from the "memory" of earlier stress events due to positive autoregulation.

Project #2. We are designing synthetic gene constructs to shape the distribution of protein levels within a cell population. For example, we can now independently adjust the mean and noise (Coefficient of Variation) of a target gene in yeast. We have also built a "linearizer" gene circuit that converts a nonlinear (sigmoidal) dose response to linear.

Project #3. We study the response of the large-scale gene regulatory networks of infectious bacteria to stress using microarray data. We identify distinct sets of transcriptional subnetworks (origons) that are affected at various times following exposure to stress. These results open the door for a system-level understanding of the response of infectious microbes to stress, as well as their drug tolerance or drug resistance.

Project #4. We are involved in the analysis and interpretation of the large-scale proteomics/drug screening/siRNA data of cancer cell lines collected at our department in the Gordon Mills laboratory.

Selected Publications:

Nevozhay D, Adams R, Murphy K, Josic K, Balázsi G (2009). Negative autoregulation linearizes the dose response and suppresses the heterogeneity of gene expression. Proc. Nat. Acad. Sci., USA. 106(13), 5123-5128.

Balázsi G, Heath A, Shi L, Gennaro ML (2008). The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Systems Biol. 4:22.

Blake WJ, Balázsi G, Kohanski MA, Isaacs FJ, Murphy KF, Kuang Y, Cantor CR, Walt DR, Collins JJ (2006) Phenotypic consequences of promoter-mediated transcriptional noise. Mol Cell 24:853-865.

Balázsi G, Barabási AL, Oltvai ZN (2005) Topological units of environmental signal processing in the transcriptional regulatory network of Escherichia coli. Proc Natl. Acad. Sci. U. S. A. 102:7841-7846.

Additional Publications