Research objectives and content
Over 200 mutations have so far been identified in androgen receptor from patients with physiological defects ranging from androgen insensitivity, X-linked spinal and bulbar muscular athropy to prostate cancer. These mutant receptors have been analyzed in in vitro DNA binding studies and in cultured cell lines to determine defects in their functional activities. These experiments are however inadequate, as they do not provide the full documentation of the defects of the androgen receptor in the context of an intact animal. For decisions to be made regarding possible therapeutic approaches to the treatment of such disorders, it is important to generate animal models with the mutant androgen receptor. This can be achieved with the use of transgenic animal techniques and homologous recombination in the mouse. The resulting animals will be used for studies on defects in the androgen signalling pathway in an intact animal and for analyzing the efficacy of synthetic steroids as therapeutic substances in androgen related disorders.
Training content (objective, benefit and expected impact)
The aim of this application is to provide me with the opportunity to obtain an intensive training in Molecular Endocrinology in a laboratory that has an outstanding record and reputation in this field. My training programme would hopefully include the molecular action of classical steroid receptors, particularly the androgen receptor, its role in disorders such as prostate cancer, X-linked spinal and belabour muscular atrophy and undergone insensitivity. Through the establishment of mouse model for these disorders, I hope to bridge the gap theat separates present studies in in vitro cell culture systems and the real in vivo function of the androgen receptor.
Links with industry / industrial relevance (22)
The laboratory I am planning to join collaborate with pharmaceutical firms (Schering, Berlin and Jenapharm, Jena) specialized in steroid hormone receptor work. Through my work in this laboratory, I hope to gain an insight into the activities in industry and possibly to participate in some of the joint projects they have with my host laboratoy. The animal models that I plan to generate would also be useful for joint studies with these industrial firms.