Research objectives and content
Apoptosis has been only recently acknowledged as possible contributor to toxicological and pathological neurodegeneration. However, the molecular mechanism underlying apoptosis has been studied mainly in non-neuronal cells. Therefore, the aim of this research proposal is to study the involvement of an apoptosis-associated gene-family, the bcl2-gene family, in the onset of an in vivo model system of neuronal apoptosis, i.e. adrenalectomy-induced apoptosis in the rat hippocampus. Firstly, I will study the expression of different members of the bc1-2 family by in situ hybridization and quantitative PCR experiments. Secondly, the effect of up-and down regulation of relevant members on apoptosis will be studied using hippocampal slices treated genetically modified retroviruses. The results of the proposed research may provide new leads for pharmacological intervention strategies for several neurological disorders in response to toxic agents.
Training content (objective, benefit and expected impact)
Objective: Understanding molecular mechanisms regulating the process of neuronal cell death.
Benefit: By learning the molecular biology in addition to her cell biological knowledge of the process of cell death, the applicant will be able to perform research in a more multidisciplinary way. This multidisciplinary approach is nowadays required in the field of pharmacology and toxicology, i.e. apoptosis. Through working at the ICRF, which is a center of excellence on molecular biology of apoptosis the quality of the molecular biological training is ensured.
Impact: The acquired knowledge of introducing genes by viral transduction and successful manipulation of apoptosis in the brain may have impact for the clinical situation and provide valuable clues for development of gene therapy in treatment of neurodegenerative diseases.