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Researchers at Rice, UH use NIH exploratory grant to analyze bacterial decision making

Systems and synthetic biologists inspired by light-based
synthetic gene platform

By Shawn Hutchins
Rice BIOE News

Researchers at Rice University and the University of Houston are applying the latest techniques in systems and synthetic biology to study how Bacillus subtilis bacteria decide to reproduce or sporulate.

The research, which is supported by a new two-year exploratory/developmental grant by the National Institutes of Health, will provide a systems-level understanding of B. subtilis sporulation and stress-response.

Dozens of studies over the past 25 years have identified a network of more than 30 genes that B. subtilis uses to control sporulation. When food is plentiful, this network is largely silent. But during times of starvation, the genes work in concert to form spores.

Rice University’s Jeff Tabor and Oleg Igoshin (left-right) are applying the latest techniques in systems and synthetic biology to study how Bacillus subtilis bacteria decide to reproduce or sporulate. 
“When confronted with environmental change bacteria use genetically encoded sensors and circuits to respond to such change. It’s a feature that has enabled them to thrive in unpredictable natural environments,” said Jeff Tabor, a lead researcher on the new grant and an assistant professor of bioengineering and of biosciences at Rice. Tabor specializes in building sensors and circuits for scientific and engineering applications.

Through collaboration with Rice bioengineer Oleg Igoshin and University of Houston biochemist Masaya Fujita, the new research aims to understand the dynamic nature of signals that control B. subtilis sporulation.

For this project, Tabor and Sebastian Castillo-Hair, a third-year bioengineering graduate student co-advised by Tabor and Igoshin, will adapt an optogenetic technology for using time-varying light signals and light-switchable bacterial two-component systems from E. coli to the evolutionary distant B. subtilis.

Development of this technology will enable the team to dynamically interrogate the genetic circuits that regulate the B. subtilis sporulation decision. Then using a combination of experimental and computational approaches, the researchers will investigate how different rates of activation of the major sporulation regulators impact the circuit functions and downstream cellular processes.

Igoshin, an associate professor of bioengineering, has developed detailed mathematical models of the complex regulatory networks that cells use to make such decisions. Igoshin says the new model will study how sporulation outcome depends on the dynamics of the network components, that is the precise way their concentrations change in time. “This should have a tremendous impact on how we think about cellular decision-making. Until now, no experimental tools to directly test such predictions were possible. The optogenetic technology developed in this project will enable such tests,” Igoshin said.

Masaya Fujita, an associate professor in the Department of Biology and Biochemistry at the University of Houston will help with the genetic engineering of B. subtilis strains and oversee measurements of the sporulation efficiencies in different conditions.

“Thanks to this award we will develop a methodology to dynamically perturb and observe protein activities in gene circuits in real time. Through this technology we will gain crucial insights about cellular decision-making and differentiation” said Tabor. “Since the circuits that we plan to study are found among medically important spore-forming bacteria including B. cereus, B. anthracis, and C. difficile, our result could provide a basis for design of new antibacterial agents.”