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Variability and Robustness in Bio-molecular systems (VARB)
Start date: Jan 1, 2009, End date: Oct 31, 2013 PROJECT  FINISHED 

Cells process information using biochemical networks of interacting proteins and genes. We wish to understand the principles that guide the design of such networks. In particular, we are interested in the interplay between variability, inherent to biological systems, and the precision of cellular computing. To better understand this interplay, we will: (1) Characterize the extent of gene expression variability and define its genetic determinants, (2) Reveal how variability is buffered and (3) Describe instances where variability (or 'noise') is an integral part of cellular computation. The study will be conducted in the multidisciplinary atmosphere of our lab, by students trained in physics, computer science, chemistry and biology. Specific issues include: 1. Gene expression variability: we will focus on the influence of chromatin structure on gene expression variability, as suggested by our bioinformatics analysis. 2. Robustness and scaling in embryonic patterning: We will study the means by which fluctuations are buffered during the development of multicellular organisms. We will focus on the robustness of morphogen gradients to protein levels, and on the ability to maintain proportionate pattern in tissues of different size. 3. Noise-driven transitions in a fluctuating environment: Our preliminary results suggest that noise plays an integral part in phosphate homeostasis in S. cerevisiae. We will characterize the role of noise in this system and study its evolutionary implications. Together, our study will shed light on one we believe to be the fundamental challenge of biological information processing: ensuring a reliable and reproducible function in the highly variable biological environment. Our study will furthermore define novel multidisciplinary, system-level paradigms and approaches that will guide further studies of bio-molecular systems
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