Growth-Specific Programs of Gene Expression in Yeast

Edo Airoldi

Growth is a fundamental process in cellular proliferation, and its disruption plays a role in a variety of disorders from viral infection to cancer. Cellular growth is so essential that our ability to probe and reveal the inner mechanisms of the cell crucially depends on our ability to control it. In fact, most experiments are performed on cellular cultures growing in artificial environments. An important instance of this problem is the investigation of environmental stress response (ESR) in yeast. In this setting, each gene's transcriptional response may be considered to arise from a mixture of two extreme models: either a gene is expressed directly in response to stress, or it is expressed purely in response to the change in growth rate caused indirectly by stress. In practice, the net effect of the ESR is confounded in the magnitude of transcriptional responses, due to the mix of growth-related and stress-related effects. Our goal is thus to isolate the effects of these two extremes, or in the general case, to deconvolute transcriptional responses to primary biological stimuli from responses from indirect growth effects. Statistical analysis of a carefully designed experimental probe enables us to estimate (in both continuous and batch cultures) the ``instantaneous growth rate'' of new collections of expression data, and to establish the portion of response that cannot be attributed to growth. The effective growth rate of a cellular culture is a novel biological concept, and it is useful in interpreting the system-level connections among growth rate, metabolism, stress and the cell division cycle.

References: Coordination of Growth Rate, Cell Cycle, Stress Response and Metabolic Activity in Yeast. (Molecular Biology of the Cell). Matthew J. Brauer, *Curtis Huttenhower, *Edoardo M. Airoldi, Rachel Rosenstein, John C. Matese, David Gresham, Viktor M. Boer, Olga G. Troyanskaya & David Botstein.

Growth-specific programs of gene expression in yeast. (manuscript). *Edoardo M. Airoldi, *Curtis Huttenhower, David Gresham, David Botstein & Olga G. Troyanskaya.