Design principles of biological circuits
Cells are constantly "making decisions" - monitoring their environment, modulating their metabolism and 'deciding' whether to divide, differentiate or die. For this, they use biochemical circuits composed of interacting genes and proteins. Advances over the past decades have mapped many of these circuits. Still, can we infer the underlying logic from the detailed circuit structure? Can we deduce the selection forces that shaped these circuits during evolution? What are the principles that govern the design and function of these circuits and how similar or different are they from principles that guide the design of man-made machines?
The interplay between variability and robustness is a hallmark of biological computation: Biological systems are inherently noisy, yet control their behavior precisely. Research projects in our lab quantify biological variability and identify its genetic origins, examine how variability is buffered by molecular circuits and investigate whether variability can in fact be employed to improve cellular computation.
We encourage a multi-disciplinary approach, combining wet-lab experiments, dynamic-system theory and computational data analysis. This is achieved through fruitful interactions between students with backgrounds in physics, biology, computer science, mathematics and chemistry.
Meyer bulding 404
Weizmann Institute of Science
FEATURED ARTICLE The Genetic Requirements for Pentose Fermentation in Budding Yeast Karin Mittelman & Naama Barkai
Cells grow on a wide range of carbon sources by regulating substrate flow through the
metabolic network. Incoming sugar, for example, can be fermented or respired, depending on
the carbon identity, cell type, or growth conditions. Despite this genetically-encoded flexibility
of carbon metabolism, attempts to exogenously manipulate central carbon flux by rational
design have proven difficult, suggesting a robust network structure. To examine this robustness,
we characterized the ethanol yield of 411 regulatory and metabolic mutants in budding yeast.
The mutants showed little variation in ethanol productivity when grown on glucose or galactose,
yet diversity was revealed during growth on xylulose, a rare pentose not widely available in
nature. While producing ethanol at high yield, cells grown on xylulose produced ethanol at high
yields, yet induced expression of respiratory genes, and were dependent on them. Analysis of
mutants that affected ethanol productivity suggested that xylulose fermentation results from
metabolic overflow, whereby the flux through glycolysis is higher than the maximal flux that can
enter respiration. We suggest that this overflow results from a suboptimal regulatory
adjustment of the cells to this unfamiliar carbon source. ....Read more...
Departments of Molecular Genetics and Physics of Complex Systems