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 Expression homeostasis during DNA replication Yoav Voichek*, Raz Bar-Ziv*, Naama Barkai
Genome replication introduces a stepwise increase in the DNA template available for transcription. Genes replicated early in S phase experience this increase before late-replicating genes, raising the question of how expression levels are affected by DNA replication. We show that in budding yeast, messenger RNA (mRNA) synthesis rate is buffered against changes in gene dosage during S phase. This expression homeostasis depends on acetylation of H3 on its internal K56 site by Rtt109/Asf1. Deleting these factors, mutating H3K56 or up-regulating its deacetylation, increases gene expression in S phase in proportion to gene replication timing. Therefore, H3K56 acetylation on newly deposited histones reduces transcription efficiency from replicated DNA, complementing its role in guarding genome stability....Read more...
Departments of Molecular Genetics and Physics of Complex Systems