Collaborative Research: H-NOX homologues in biofilm formation: A combined molecular and systems level approach.

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Biofilms are stationary communities of bacteria that adhere to various surfaces. Inhabitation of a biofilm often makes bacteria resistant to clearance strategies that are effective against their free-living (planktonic) counterparts. As such, understanding the molecular cues that promote switching between the stationary and untethered lifestyles can guide our responses to biofilm formation in both beneficial and detrimental contexts. This project seeks to characterize cellular changes accompanying biofilm formation at the systems level, as well as the role of a particular family of sensor proteins in biofilm formation/dissolution at the molecular level. Student training is a major emphasis of this work. Students will be co-mentored by a team of scientists with expertise in diverse techniques and will have the opportunity to conduct transformative research at national laboratories. A proteomics workshop for graduate students will also be developed to train the next generation of scientists in this cutting-edge technology.The scientific objective is to define conserved and novel mechanisms of bacterial signaling relevant to biofilm formation across multiple species using advanced structural and proteomics methods. At the molecular level, this will include determining the mechanisms by which the heme nitric oxide/oxygen binding proteins (H-NOX) sense oxidants and/or nitric oxide (NO), resulting in biofilm formation or dissolution. Structure determination using X-ray crystallography and nuclear magnetic resonance (NMR) will be utilized as well as X-ray absorption fine-structure (EXAFS). Advanced proteomics and phosphoproteomics will detail the signaling networks involved in this process at the organismal level using H-NOX deletion mutants. This combination of approaches will yield detailed mechanistic understanding of an important signaling process and how it has evolved to meet the needs of diverse bacterial species.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.