Research objectives and content
The JunD protein clearly functions differently from related Jun proteins, but it's precise role in physiological and cellular response to stimuli is unknown. The surprising observation that inactivation of the junD gene results in mice that are viable presents a unique and powerful tool for analysis of JunD function. Furthermore, our results are unlike those obtained by inactivating other AP- 1 genes or genes known to inhibit cell growth. These mice will provide exciting insights into the specific function of JunD by allowing a detailed analysis at the molecular, cellular and physiological levels. The proposed study of fibroblast and Iymphocyte function in vitro should highlight JunD-specific function in controlling cell growth and particular induced gene expression programmes. We expect to uncover specific JunD-regulated events associated with cell growth, cell death, transformation and cell cycle. Furthermore, we will gain an appreciation of overlapping and non-redundant roles for different Jun members. This understanding will serve as the basis for investigation in vivo analysis of JunD function in physiology and pathology.
Training content (objective, benefit and expected impact)
This study will allow me to expand my knowledge and expertise in cellular and molecular biology. I will be able to contribute significantly my background in leukocyte gene expression, cellular interactions with the extracellular environment, and growth and movement of transformed cells. It will give me training in several important new areas including transcription factor biochemistry, mouse genetics and physiology, isolation of primary cell cultures etc. This breadth will strengthen my ability to function as a competent and creative scientist within the European community. I will benefit tremendously from the expertise of the Yaniv lab and the superb scientific environment of the Institut Pasteur. The results obtained will be of significance to many groups interested in the specific functions of Jun proteins and the general understanding of the processing of information from external stimuli.