Periplasmic Chaperone Network Organization and Mechanism

This proposal seeks unifying physical principles that define rules of life in bacteria, which are among the most abundant forms of life on earth. The research addresses the essential process of bacterial cell surface formation in these organisms. It will serve as a roadmap for how cell surface formation may occur in evolutionary related systems in higher life forms. The broader impacts include the intellectual power of connecting physical observations to principles of life, and the research activities benefit society at large through novel insights about living systems. The work offers meaningful opportunities for undergraduate research experiences and trains graduate students in multidisciplinary approaches to science. The outcome from these efforts will be the training of diverse and creative investigators that will increase creativity and productivity in the STEM fields in our country. The periplasm of Gram-negative bacteria is devoid of an external energy source to achieve sorting and folding of the membrane proteins that are found in their outer membranes. The research interrogates how this process is achieved solely through thermal energy, thermodynamic binding potentials, kinetic on- and off-rates and local cellular expression levels of the periplasmic chaperones. This research will interrogate the periplasmic protein interaction network using a multi-scale approach that will include structural measurements of key binding events, solution conformation determinations and calculations of unfolded membrane protein reactants, computational modeling of experimental data, and cellular localization and dynamics experiments in vivo. The results of this research will be integrated into a global, systems-wide understanding of the chaperone network in the bacterial periplasm. This project is funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Sciences 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.