Sensory Regulation of Bacterial Behaviors
The overarching goal of my research program is to understand how pathogenic and environmental bacteria integrate metabolism with environmental sensing to survive and thrive. Central to this effort is uncovering how bacteria process and reconcile competing physical, chemical, and biological signals to persist in dynamic environments. Accordingly, we are working on the projects outlined below that are unified by a central theme of deciphering the sophisticated molecular sensing and regulatory networks that bacteria use to optimize their survival, virulence, and adaptation strategies. By understanding these fundamental control systems – from light-sensing cascades to flagellar regulation to predatory mechanisms – our research aims to exploit bacterial regulatory vulnerabilities to develop innovative therapeutic approaches against antibiotic-resistant pathogens.
Photo sensing in non-photosynthetic bacteria
Light is detected by photoreceptors in all domains of life. Surprisingly, photosystems in non-photosynthetic bacteria are mostly undefined. We have identified an entire photo-sensing signaling cascade in the human pathogen Pseudomonas aeruginosa —light as the input, BphP as the detector, AlgB as the signal transducer, and biofilm formation and virulence factor production as the outputs — enabling crucial insight into light-driven control of bacterial behaviors. We are characterizing the photo-sensing system and its regulon in P. aeruginosa and exploring the role of photo sensing in P. aeruginosa-host interactions. We are testing the generality/specificity of our findings in P. aeruginosa by expanding our research to include other bacteria that possess the BphP-AlgB photo-sensing system.
Polarity development in bacteria
How do bacteria count their appendages? How do bacteria sense assembly states of their nanomachines? How robust are these sensing mechanisms to environmental fluctuations? We are exploring these questions using the motility nanomachine called flagellum. We are studying the molecular mechanisms that dictate the precise number and location of flagellum assembly and the consequences of mis regulation of these processes.
Nutrient sensing in biofilms
Nutrient availability is a key sensory cue that governs different stages of the biofilm development cycle. The CbrA/CbrB two-component system is involved in nutritional adaptation in P. aeruginosa and modulates biofilm development by mechanisms that are poorly defined. In this project, we are delineating the molecular players downstream of the CbrA-CbrB cascade to gain a better understanding of how nutrient status influence key steps of biofilm development.
Convergence of sensory signaling pathways
It is imperative that bacteria decode and integrate varied sensory inputs to make key transitions such as whether to launch a virulence program or remain in a stealth mode to avoid host immune factors. However, how bacteria integrate diverse sensory information is poorly understood. Our goal is to identify the components that connect different signaling pathways. To pursue this goal, we will define how information from photo sensing, nutrient sensing and quorum sensing is combined at the molecular and cellular scales to control bacterial behaviors.
