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
Rehovot 76100
May 2014
Congratulations to Zvika, Noam and Eyal on graduating! Here's a picture from the ceremony (May 15th 2014):

May 2014
Congratulations to Inna and Danny for their amazing new paper in Development on scaling morphogen gradients during tissue growth

February 2014
Congratulations to Eyal and Yossi for handing in their M.Sc Thesis

February 2014
The Barkai Lab had a great time in Ilanit FISEB 2014! In one of the nights we went bowling...

January 2014
Congratulations to Noam Vardi on finishing his PhD! From now on - Dr. Vardi! You can read his paper from Current Biology on how yeast cells escape commitment using noise here .

January 2014
Congratulations to Zvika Tamari on finishing his PhD! Dr. Tamari!

January 2014
The Barkai lab would like to wish Mazal Tov to Noam Ohana on finishing his MSc and good luck in his future endeavors!

December 2013
Barkai lab wishes you happy holidays!

October 2013
Congratulations to the lab Vollyaball team on winning in the latest departmental tournament!

October 2013
On November the lab is going on a lab trip, to mark the departure of Ilya from the lab

October 2013
Congratulations to Noam V on his new paper in Current Biology!

September 2013
Next month Gilad will give a talk in the departmental seminar!

September 2013
The Barkai Lab wishes you a happy holiday!

August 2013
We would like to welcome Gilad Yaakov to the Barkai Lab!

August 2013
The Barkai Lab wishes good luck to Dana and Michal, our new M.Sc students!
Budding Yeast Escape Commitment to the Phosphate Starvation Program Using Gene Expression Noise
Noam Vardi, Sagi Levy, Michael Assaf, Miri Carmi, Naama Barkai
Current Biology (2013)

Cells must rapidly adapt to changes in nutrient availability. In budding yeast, limitation of phosphate rapidly induces the expression of the Pho regulon genes [1-4]. This starvation program depends on the transcription factor Pho4, which translocates to the nucleus within minutes when cells are transferred to a low-phosphate medium [5]. Contrasting its rapid induction, we report that the Pho regulon can remain induced for dozens of generations in cells transferred back to high phosphate levels. For example, about 40% of the cells that were starved for 2 hr maintained PHO4-dependent expression for over eleven generations of growing in high phosphate. This commitment to activation of the Pho regulon depends on two feedback loops that reduce internal phosphate, one through induction of the PHM1-4 genes that increase phosphate storage in the vacuoles and the second by induction of SPL2, which reduces incoming flux by inhibiting low-affinity transporters. Noise in SPL2 expression allows stochastic repression of the Pho regulon in committed cells growing at high phosphate, as we demonstrate using a novel method, DAmP multiple copy array (DaMCA), that reduces intrinsic noise in gene expression while maintaining mean abundance. Commitment is an integral part of the dual-transporter motif that helps cells prepare for nutrient depletion...

Departments of Molecular Genetics and Physics of Complex Systems