Objective In this proposal, Dr. Ruthstein and her new group at the chemistry department in Bar-Ilan University, Israel, will determine the sensing and transcription mechanisms of metal ion sensors in bacteria. Metals are commonly found as natural constituents of proteins; however, many metal ions can be toxic when free in biological fluids. Hence, microorganisms have evolved considerable regulatory machinery to control the intracellular and extracellular concentrations and types of metal ions encountered in their microenvironments. Gene regulatory proteins, called metal sensor proteins mediate this metal traffic control. These proteins have evolved metal coordination sites that “sense” specific metal ion and activate or inhibit DNA binding or transcription activation, thereby controlling the expression of genes that mediate what must be an exquisitely selective adaptive response. In order to understand how the sensor senses a specific metal and by this initiates a biological process, one has to be able to probe strutuctural changes that occur in the protein as a function of binding of the correct and wrong metal ion, and the binding of the DNA. This work will use site-directed spin labeling together with pulsed electron paramagnetic resonance spectroscopy (EPR) to shed light on such processes. EPR is an excellent tool to resolve systems that evolve protein-protein interaction and protein-DNA interaction. Distances up to 80 Å between two paramagnetic spin labels can be measured by pulsed EPR. In some cases, the measurement of one distance (or a few) is sufficient to establish the plausibility of a mechanism or corroborate a proposed structure. This work will initially focus on two Cu+ sensors (CsoR, CueR) from CsoR and MerR families. The first family inhibits DNA binding upon metal binding and the second activates transcription, but the research will extend in the future to other metal sensors from each of the families. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesgeneticsDNAengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsnatural sciencesphysical sciencesopticsspectroscopy Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2011-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator BAR ILAN UNIVERSITY EU contribution € 100 000,00 Address BAR ILAN UNIVERSITY CAMPUS 52900 Ramat Gan Israel See on map Activity type Higher or Secondary Education Establishments Administrative Contact Estelle Waise (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data