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.
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Weizmann Institute of Science
FEATURED ARTICLE The Cost of Protein Production Moshe Kafri*, Eyal Metzl-Raz*, Ghil Jona,
Cell Reports (2016)
The economy of protein production is central to cell
physiology, being intimately linked with cell division
rate and cell size. Attempts to model cellular physiology
are limited by the scarcity of experimental
data defining the molecular processes limiting protein
expression. Here, we distinguish the relative contribution
of gene transcription and protein translation to
the slower proliferation of budding yeast producing
excess levels of unneeded proteins. In contrast to
widely held assumptions, rapidly growing cells are
not universally limited by ribosome content. Rather,
transcription dominates cost under some conditions
(e.g., low phosphate), translation in others (e.g., low
nitrogen), and both in other conditions (e.g., rich media).
Furthermore, cells adapted to enforced protein
production by becoming larger and increasing their
endogenous protein levels, suggesting limited competition
for common resources. We propose that
rapidly growing cells do not exhaust their resources
to maximize growth but maintain sufficient reserves
to accommodate changing requirements...Read more...
Departments of Molecular Genetics and Physics of Complex Systems