Rudolf-Virchow- Centre, DFG-Research Centre for Experimental Biomedicine
&
Institute for Virology and Immunobiology, University of Würzburg, Germany
Proposal:
*Post*-*doc* *position* (E13); BMBF-Project GoBio 03115031
Project Supervisors:
Dr. T. Kerkau/ Dr. N. Beyersdorf/ Prof. Dr. T. Hünig
(Institut für Virologie und Immunbiologie, Universität Würzburg, Versbacher Str. 7, 97078 Würzburg;
E-mail: kerkau@mail. uni-wuerzburg. de),
PD Dr. R. Jahns/Prof. Dr. M.J. Lohse
(Rudolf Virchow Zentrum und Institut für Pharmakologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg; E-mail: jahns_r@klinik. uni-wuerzburg.de)
Funding Availability:
*Post*-*doc* fellowship; funding available from the BMBF research project
GoBio
FKZ 03115031
Application Deadline:
As soon as possible, latest june 30, 2007.
Subject: Beta1-receptor directed autoimmunity.
Recent evidence indicates that autoantibodies directed against cell surface molecules criti-cally involved in the regulation of cardiac function (i.e., the beta1-adrenergic receptor) may play a pivotal role in the development and course of dilated cardiomyopathy [1, 2]. Such antibodies are thought to act as allosteric regulators of receptor activity, most likely by stabilizing a chronic active "harmful" receptor conformation. In Lewis rats, monthly immunization with the 2nd extracellular loop of the beta1- receptor (ß1-ECII; 100% sequence-identity human/rat) results in both, the generation of activating receptor-antibodies and progressive dilated cardiomyopathy.
Application of a novel ß1-ECII-homologous cyclopeptide (ß1-ECII-CP) designed to neutralize functional anti-ß1-ECII antibodies prevents the development of cardiomyopathy. In overt disease, ß1-ECII-CP even fully reversed the cardiomyopathic phenotype. In these previous studies ß1-ECII- CP induced a rapid decrease and finally nearly complete cessation of anti- ß1-ECII-production despite continued monthly boosts with the receptor- antigen. Thus, besides its scavenger function the ß1-ECII-CP seems to have further immunomodulatory features.
The proposed project deals with the characterization of the immunologic properties of the cyclopeptide both in vitro and in vivo. Scheduled experiments comprise the analysis and characterization of T and B cells involved in the induction of tolerance , including T-cell transfer experiments and the generation of monoclonal rat anti-ß1-ECII- antibodies. The aim is to further elucidate the immunological processes involved in induction and reversal of cardiac auto-immune damage, both in rats and in patients. The work will be carried out under the auspices of the
experienced staff of the department of immunology (Institut für Virologie und Immunbiologie) and the Rudolf-Virchow- Centre (DFG-Research Centre for Exp. Biomed.).
1. Jahns R, Boivin V, Hein L, et al.: Direct evidence for a beta1-adrenergic receptor directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. J. Clin. Invest. (2004) 113:1419-1429. 2. Jahns R, Boivin V, and Lohse MJ: Beta1-adrenergic receptor function, autoimmunity, and pathogenesis of dilated cardiomyopathy. Trends Cardiovasc Med (2006) 16:20-24.
*Requirements: *
Interested candidates should have a recent Ph.D. in immunology or related fields. Experience in cellular immunology or molecular biology is advantageous.
*Contact:*
Thomas Kerkau
Versbacher Strasße 7
Würzburg, Germany 97078
*Phone:* +4993120149169
[sursa beasiswa]
If you want to receive academic resources in your e-mail on daily basis, please subscribe to 10resources-subscribe@yahoogroups.com.
If you want to publish your announcement, please send it to riliescu2000@yahoo.com.
