NSF East Asia and Pacific Summer Institute (EAPSI) for FY 2013 in Singapore

Defalco Louis, Bloomfield NJ

Investigators

Abstract

This action funds Louis DeFalco Jr. of the University of Connecticut to conduct a research project in Biological Sciences during the summer of 2013 at the National University of Singapore located in Singapore. The project title is "Exploring the Solution Behavior of the Ribosomal Translation Factor BipA." The host scientist is Dr. Ganesh Anand. Coordinated global regulation of protein synthesis is essential for bacterial survival in adverse growth conditions such as amino acid starvation, temperature shock or oxidative stress. BipA is a highly conserved prokaryotic translational GTPase (hydrolase enzyme) whose interactions with the ribosome are dictated by guanine nucleotide pools in the cell, specifically levels of hydrolyze guanosine triphosphate (GTP) and guanosine pentaphosphate (ppGpp), an alarmone responsible for adaptation to adverse growth conditions in microorganisms. In this manner, BipA operates as a metabolic sensor, acting as the mediator between cellular processes, alerting the bacteria to current environmental conditions. This project determines how the solution behavior of BipA is altered in response to guanine nucleotide binding via hydrogen/deuterium exchange experiments with mass spectrometry detection (HDXMS). This technique is used to study the formation of both binary (BipA:GTP and BipA:ppGpp) as well as the ternary 30S:BipA:ppGpp complex. Data gathered from the HDXMS studies provides the foundation for understanding how particular dynamic motions brought about by either GTP or ppGpp binding contribute to the formation of the two BipA:ribosomal species. This data serves to explicate how critical information concerning the cellular environment is conveyed between BipA and the ribosome to elicit an appropriate cellular response. Broader impacts of an EAPSI fellowship include providing the Fellow a first-hand research experience outside the U.S.; an introduction to the science, science policy, and scientific infrastructure of the respective location; and an orientation to the society, culture and language. These activities meet the NSF goal to educate for international collaborations early in the career of its scientists, engineers, and educators, thus ensuring a globally aware U.S. scientific workforce. Furthermore, Singapore?s status as a leader in the burgeoning medical tourism industry reflects a wider shift in the direction of global economic competition and represents a trend towards the expansion of our global community. As patients increasingly seek reasonable value for high quality medical treatment, frequent travel affords aggressive strains of microorganisms, once isolated to hospital settings, the opportunity to spread from region to region. Such proliferation of these microbes may cause a rise in communicable disease rates leading to epidemics in the near future. A focused understanding of the requirements for essential biological processes occurring in infectious organisms can lead to the rational design of targeted antibiotics capable of treating multiple types of infection in public and clinical settings worldwide.