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Contact Information

Oleg Igoshin
Associate Professor
Dept. of Bioengineering
Center for Theoretical and Biological Physics
MS142, P.O.Box 1892
Houston, Texas
Email: igoshin@rice.edu

Office: BRC-767
Lab: BRC-750E/F

Phone:(713)348-5502 (OI))

Research Projects

Evolutionary design principles of bacterial stress response

Two-component system architecture
When exposed to detrimental conditions such as harsh environment, antibiotics or immune response, bacteria are able to survive by switching their gene expression program to "stress-response" mode. We are interested in understanding the overall organization of biochemical networks involved in stress-sensing and responding in particular model systems as well as formulating general principles of stress-response across bacterial species. Despite conservation of their regulatory core, functional networks responding to stress display variations in their architectures. We want to understand the evolutionary design principles of these networks by correlating these variations with the different regulatory demands. In particular, we are interested in the networks characterizing bacterial sigma factors and two-component systems ‒ two widespread mechanisms of master level regulation of bacterial gene expression.

Bacterial differentiation, bet-hedging and stochastic decision making hysteretic switch controls sporulation in B. subtilis

Due to their small size gene expression noise is unavoidable in bacteria. How did they learn to cope with it or use it to their advantage? Using Bacillus subtilis as model system we collaborate with Masaya Fujita (U Houston) to study how model bacteria stochastically decide to undergo sporulation. We are also interested in the ways gene expression noise affects evolution of biochemical network architecture.

Mechanisms and dynamics of genetic regulation in hematopoietic stem cells

All types of blood cells in our bodies are formed through differentiation of hematopoietic stem cells. Ability of these cells to switch between proliferation and differentiation is determined by the dynamics of their genetic networks. We aim to understand the relationship between feedback architecture of these networks and resulting dynamical properties. We are also interested in general biophysical mechanisms of gene regulation by distant enhancers.

Spatial organization, signaling and motility in bacterial biofilms

In recent years the ubiquity of microbial communities in nature has become apparent, for instance most bacteria related to human diseases are associated with biofilms. Myxococcus xanthus is not a pathogen however complex patters formed by these bacteria are often viewed as a model system of multicellular bacterial development. In collaboration with experimental labs of  Larry Shimkets (University of Georgia) and Heidi Kaplan (UTH TMC) we work on using a combination of mathematical modeling and statistical image processing to understand spatial organization and dynamics of the patterns formed by M. xanthus during vegetative and starvation conditions.

Host-pathogen interactions during TB infection

Stress responce netwrok in TBThe bacteria that cause tuberculosis (TB), Mycobacterium tuberculosis, can transition into a dormant state to ward off attacks from antibiotics and the immune system. As a result infection can remain latent for years until the patient is immunocompromised. The mechanisms of switching to and from dormancy require system-level studies of the mutual interaction between host cells and pathogenic bacteria. In collaboration with experimental and clinical microbiologist we aim to uncover the mechanistic basis of the switching.

Characterization of CRISPRi Dynamics Using Optogenetics and Mathematical Modeling

CRISPR interference (CRISPRi) can be used to repress transcription of virtually any gene in bacteria, yeast, or mammalian cells. In this system, inactivated nuclease dCas9 forms a complex with a 102-nucleotide single guide RNA (sgRNA), which is then directed to a segment of DNA complementary to a 20-nucleotide region in the sgRNA. If the targeted DNA segment is a promoter or the coding region of a gene, dCas9 will then block transcription initiation or elongation, effectively acting as a transcriptional repressor. By designing sgRNAs with different specificities, a large number of repressors can be engineered. This technology has enabled the construction of multilayered digital synthetic gene circuits of unprecedented complexity. Although the steady-state response from sgRNA expression to output transcription rate has begun to be studied, a thorough characterization of CRISPRi dynamics has not been performed. This would enable researchers to create precise, time varying perturbations in a wide range of natural gene networks, and establish design principles for engineering analog dynamic gene circuits. We are using our previously developed CcaS/CcaR optogenetic system to study CRISPRi repression dynamics in E. coli. By using light-induced sgRNA expression and mathematical modeling, we are characterizing features such as asymmetric repression/derepression dynamics, influence of the copy number of the target promoter, and the effect of dCas9 loading expression of a different sgRNA that competes for dCas9  on the system performance. This work should contribute to elucidate design rules that allow the reliable and predictable construction of analog synthetic gene circuits.