Systems Biology

The success of the human genome project has ushered in a new era that emphasizes a systemic or integrated approach to ascertain the cellular behavior arising from complex cellular networks. Scientists are now embarking on a quest to elucidate the organization and control of cellular networks that underlie the phenotypic behavior of a cell; these are the so-called ``omics'' such as genomics, transcriptomics, proteomics, metabolomics. Fueled by recent advances in molecular biology providing high-throughput and in-depth data of gene and protein interactions, it is increasingly clear that cell behaviors arise from complex interactions among the genes and proteins through crossover and cascade regulations and signal transductions, and thus can only be explained through a system-level understanding of these interactions. This is the goal of systems biology, which involves application of systems theoretic approaches and integration of experimental and computational research.

Control system approaches are instrumental in systems biology. Several concepts from control engineering, in particular robustness, have been used to define many characteristics of cellular behavior. Robustness refers to the ability of a cell to maintain its functions (phenotype) under intrinsic and extraneous uncertainties. In biological systems, uncertainties can arise from the inherent stochastic nature of gene expression (intrinsic) or from variations in the nutrients and signals concentration (extraneous). There exists a consensus in the literature that the complexity in the cellular network arises from the regulation and control required to achieve such robust behaviors. Also, one salient feature of high robustness is the existence of fragility points in the cellular network to which a small perturbation can lead to catastrophic consequences. The understanding of robustness and fragility trade-offs in biology can help elucidate disease development in healthy cells and identify possible drug targets in diseased cells. Our research focus is to ascertain the underlying design principles of robustness in biology through model development and analysis. Specific applications of interest include circadian rhythm gene regulation, cell cycle control, unfolded protein response, and ERK activation in staphylococcal enterotoxin response.
Topics we are currently developing:

• Developing techniques to analyze Circadian Rhythms.
• Applying robust control theory to elucidate control mechanisms behind signal transduction networks.
• Developing BioSens as a tool to analyze the sensitivity of biochemical networks