Laboratory Profile Principal Investigator: Shimon Schuldiner Molecular Mechanism of Transport of Neurotransmitters and Antibiotics Location: Silberman Wing 1, 3rd. floor Room 1-339 Communication: E.Mail: shimon.schuldiner@huji.ac.il Phone: 6585992 Web: http://biolchem.huji.ac.il/shimons/ Brief Description of Research: Neurotransmitters are actively stored in synaptic vesicles by proteins such as VMAT. VMAT is also capable of transporting toxic compounds into subcellular compartments, conferring resistance against their harmful effect. VMAT displays weak but distinct amino acid sequence similarity with bacterial multidrug transporters (MDTs) that confer resistance against antibiotics. Bacterial MDTs studied in our laboratory provide insights into molecular mechanisms and evolution pathways. (for more details, please see website). Techniques used include: molecular biology (site directed mutagenesis, directed evolution and more); microbiology (bacteria and yeast) for the identification of mutants and phenotype measurements; biochemistry, for purification and characterization of membrane protein; tissue culture, for evaluation of activity of neurotransmitter transporters; structural biology, for evaluation of predicted structure Proposed Research Projects: Topic 1: Evolution of specificity and function of multidrug transporters. Studies using directed evolution. Topic 2: Mechanism of action of neurotransmitter transporters: identification of conformational changes essential for transport activity.