CHIP:Research

Research Interests

Mathematical/computational modeling and experimental characterization of biomolecular interaction networks to unravel molecular mechanisms underlying cellular survival and evolution in stress.


 * 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 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 microbes and cancer cells to stress using published microarray data. We identify distinct sets of transcriptional subnetworks that are affected following exposure to stress. These results open the door for a systems-level understanding of the response of infectious microbes or cancer cells to stress, providing insights into their drug tolerance or drug resistance.


 * Project #5. We analyze and interpret the large-scale proteomics/drug screening/siRNA data collected at our department in the Gordon Mills laboratory. We are inferring signaling networks based on experimental data, and study their overlap with known interaction networks.

References:

1. Blake WJ, Balázsi G, Kohanski MA, Isaacs FJ, Murphy KF, Kuang Y, Cantor CR, Walt DR, Collins JJ. Phenotypic consequences of promoter-mediated transcriptional noise. Mol. Cell 24(6):853-865 (2006). 2. Murphy, KF, Balázsi G, Collins JJ. Combinatorial promoter design for engineering noisy gene expression. Proc. Nat. Acad. Sci., USA. 104(31):12726-12731 (2007). 3. Balázsi G, Collins JJ. Sensing Your Surroundings: Taking the inventory inside single cells. News and Views. Nature Chemical Biology 3(3):141-142 (2007). 4. Strickler JR, Balázsi G. Planktonic copepods reacting selectively to disturbances. Phil. Trans. R. Soc. B. (2007) 5. Ernst J, Beg QK, Kay KA, Balázsi G, Oltvai ZN, Bar-Joseph Z. A semi-supervised method for predicting transcription factor-gene interactions in Escherichia coli. PLoS Comput Biol. 2008 Mar 28; 4(3):e1000044. 5. Heath AP, Kavraki L, Balázsi G, Bipolarity of the Saccharomyces Cerevisiae Genome. IEEE 2nd Intl. Conf. Bioinformatics and Biomedical Engineering, 330-333 (2008). 6. 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. 4:225 (2008). 7. 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 (2009). 8. Irimia D, Balázsi G, Agrawal N, Toner M (2009), Adaptive-Control Model for Neutrophil Orientation in the Direction of Chemical Gradients. Biophys. J. 96(10), 3897-3916. 9. Veiga DFT, Dutta B, Balázsi G (2010), Network inference and network response identification: moving genome-scale data to the next level of biological discovery. Mol Biosyst. 6(3), 469-480. 10. Murphy KF, Adams R, Wang, X, Balázsi G, Collins JJ (2010), Tuning and controlling gene expression noise in synthetic gene networks. Nucleic Acids Res. 38(8), 2712-2726. 11. Balázsi G (2010), Network reconstruction reveals new links between aging and calorie restriction in yeast. HFSP Journal 4(3), 94-99. 12. Tiwari A, Balázsi G, Gennaro M, and Igoshin OA (2010), Interplay of multiple feedbacks with post-translational kinetics results in bistability of mycobacterial stress-response. Phys. Biology 7(3), 036005. 13. Nevozhay D, Adams R, Balázsi G (2011), Linearizer Gene Circuits with Negative Feedback Regulation. Methods Mol Biol. 734, 81-100. 14. Datta P, Shi L, Bibi N, Balázsi G, Gennaro ML (2011), Regulation of central metabolism genes of Mycobacterium tuberculosis by parallel feed-forward loops controlled by sigma factor E (σ(E)). J Bacteriol. 193(5), 1154-60. 15. Balázsi G, van Oudenaarden A, Collins JJ (2011), Cellular decision making and biological noise: from microbes to mammals. Cell 144(6), 910-925.

More information may be found on two other websites:

1) The GSBS website:

2) The Systems Biology website:.

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