Michael Laub, Ph.D.
Department of Biology
(617) 324-0418 (phone)
Ph.D. Developmental Biology, Stanford University, 2002
Our lab aims to understand how cells process information, make decisions, and control their own behavior. This
information-processing capability is ultimately endowed by complex regulatory networks and signal transduction
pathways, but the design and operating principles of such molecular-based circuits remain poorly understood. We
are tackling this challenge in two particular contexts.
First, we are using computational methods, coupled with biochemical and genetic tools, to study the mechanisms
by which cells maintain the specificity of signal transduction systems to prevent unwanted cross-talk. We are
tackling this problem in the context of two-component signal transduction systems, the predominant family of
signaling proteins in bacteria. Understanding the specificity of kinase-substrate interactions for these signaling
pathways has been largely refractory to structure-based approaches. To identify key specificity-determining
residues, we have examined patterns of amino-acid coevolution in large multiple sequence alignments of cognate
kinase-substrate pairs. We have gone on to show that a subset of these coevolving residues is sufficient, when
mutated, to completely switch the specificity of a histidine kinase, both in vitro and in vivo. Our work now enables
the rational rewiring of two-component pathways in synthetic signaling circuits as well as new investigations into
molecular evolution and the selective pressures that influence large families of signaling proteins. We are also working<
to improve algorithms for the sensitive and specific detection of amino acid coevolution in sequence alignments.
Second, we are dissecting the genetic circuitry that controls cell cycle progression and the generation of cellular
asymmetry in the bacterium Caulobacter crescentus. For this work, we combine genetics, biochemistry, microscopy,
genomics, and computational tools to map the regulatory network controlling the cell cycle and to explore how the
molecules involved are connected and orchestrated at the systems-level. In particular, we aim to understand the
architecture and role of the key feedback loops that ensure robust cell cycle oscillations.
- Skerker, J.M., Perchuk, B.S., Siryaporn, A., Lubin, E., Ashenberg, O., Goulian, M., Laub, M.T. (2008) “Rewiring the specificity
of two-component signal transduction systems”, Cell, 133, p. 1043-1054.
- Laub, M.T., Goulian, M. (2007) “Specificity in two-component signal transduction systems”, Annual Review of Genetics, 41,
- Biondi, E.G., Reisinger, S.J., Skerker, J.M., Arif, M., Perchuk, B.S., Ryan, K.R., Laub, M.T. (2006) “Regulation of the bacterial
cell cycle by an integrated genetic circuit” Nature, 444, p. 899-904.
- Skerker, J.M., Prasol, M., Perchuk, B., Biondi, E., Laub, M.T. (2005) “Two-component signal transduction pathways regulating
growth and cell cycle progression in a bacterium: a system-level analysis” PLoS Biology, 3, p. 334-353.
- Skerker, J.M., Laub, M.T. (2004) “Cell cycle progression and the generation of asymmetry in Caulobacter crescentus” Nature
Reviews Microbiology, 2, 325-37.
Last Updated: April 12, 2009