From owner-biophysics@net.bio.net Wed Jun 17 23:00:00 1998 Path: biosci!OPAL.TUFTS.EDU!akuliopu From: akuliopu@OPAL.TUFTS.EDU (Athan Kuliopulos) Newsgroups: bionet.biophysics Subject: Two Signal Transduction Postdoc Positions-Boston Date: 18 Jun 1998 07:51:57 -0700 Organization: NEMC Lines: 61 Sender: daemon@net.bio.net Distribution: world Message-ID: <35892A9E.6CABF885@opal.tufts.edu> Reply-To: "Kuliopoulos@HemOnc"@NEMC.nemc.org NNTP-Posting-Host: net.bio.net Two Postdoctoral Positions Available Molecular Cardiology Research Institute Tufts University School of Medicine-NEMC Boston, MA We have an immediate opening for two Postdoctoral Fellows to work in the field of molecular signaling and peptide-protein recognition. The projects focus on the human thrombin receptor. The thrombin receptor is activated by thrombin cleavage of the receptor exodomain and exposure of an N-terminal tethered ligand that binds to the body of the receptor. Receptor activation precipitates complex signaling events culminating in platelet aggregation, wound healing, and cellular proliferation. Since chronic activation of the receptor may lead to coronary artery disease, stroke, and other vascular diseases, preventing thrombin receptor activation is of pharmacologic interest. 1) Macromolecular Structural Studies of the Resting and Activated States of Thrombin Receptor Extracellular Domains. NMR structural studies of the thrombin receptor exodomain in activated and resting forms are currently in progress and a preliminary structure has been generated for the activated exodomain. Future projects include solving the structure of the exodomain complexed with extracellular loops. Insight into the molecular interactions between the exodomain and the body of the receptor should provide leads for the development of novel anti-thrombin receptor agents in collaboration with a pharmaceutical company. The NMR facility is located in the Medical School Biochemistry Department and current instrumentation include a new Bruker 600 MHz and updated 500 MHz magnets along with several SGI workstations. Our lab has close collaborations with NMR spectroscopists who provide additional technical expertise. 2) Thrombin-Cell Surface Protein Interactions; Development of Cell Surface-Specific Anti-Thrombotic Agents. During coagulation, the physiologic concentration of thrombin exceeds that of its thrombin receptor substrate. Therefore, thrombin has a difficult task of discriminating among the various cell surface proteins to find the receptor and cleave it in the millisecond time range. We are interested in exploring this unusual mechanism of substrate-assisted domain cleavage by thrombin and using this information to develop a novel class of cell surface anti-thrombin agents. The laboratory is located within the Molecular Cardiology Research Institute, a modern, state-of-the-art facility with a staff of 40 investigators including technical support. Qualifications for this position are a Ph.D. degree. Candidates with training in NMR who would like to acquire expertise in molecular biology are encouraged to apply. Interested candidates should e-mail a description of their research interests, a CV, and names of three references to: Athan Kuliopulos, MD., Ph.D. Assistant Professor of Medicine and Biochemistry Molecular Cardiology Research Institute Tufts-NEMC Box 832 750 Washington Street Boston, MA 02111 617-636-8482 617-636-4833 (fax) akuliopu@opal.tufts.edu .