Ziel
Several aspects of decision-making in a cell are to be addressed in the proposed program, starting from the expression and action of receptors for selected growth factors implicated in neuronal development, via signal-transducing proteins, to specific transcription factors. The growth factors of primary focus are nerve growth factor (NGF) and Insulin-like growth factor -1 (IGF-1). These studies should permit the clarification of the cell cycle specificity of NGF action, opening the way for more precise analysis of this growth factors' effects on proliferation, differentiation and survival of neuronal cell types. In the area of apoptosis, the identification of the IGF-1 and NGF survival pathways and the elucidation of the role of known viral and non-viral proteins in prevention of apoptosis will also be of significant import and impact.
Scientific context:
During development, cells are confronted with various extracellular signals that determine their fate. The precise sculpturing of an organism requires careful orchestration of proliferation, differentiation and apoptosis. Furthermore, in the adult animal, extracellular signals are essential for survival and the maintenance of the differentiated state
Several aspects of decision-making in a cell are to be addressed in the proposed program, starting from the expression and action of receptors for selected growth factors implicated in neuronal development, via signal-transducing proteins, to specific transcription factors. The end result of the signal transduction being proliferation, differentiation or maintenance of the differentiated state in models for neuronal differentiation, these studies should, in the very least, clarify the role of some key regulatory proteins in the anti-mitogenic, differentiation and survival (anti-apoptotic) effects of the growth factors studied.
The growth factors of primary focus are nerve growth factor (NGF) and Insulin-like growth factor-1 (IGF-1). These studies should permit the clarification of the cell cycle specificity of NGF action, opening the way for more precise analysis of this growth factors' effects on proliferation, differentiation and survival of neuronal cell types. The fact that the NGF receptors (TrkA and p75LNFR) are members of two families of neurotrophic factor receptors, one can hope that the conclusions drawn from the proposed program may at least serve as a model for the study of other members of the families. In the area of apoptosis, the identification of the IGF-1 and NGF survival pathways and the elucidation of the role of known viral and non-viral proteins in prevention of apoptosis will also be of significant import and impact.
Public Health context:
Increasing appearance of neurodegenerative disorders due to increased longevity (population ageing). Neurodegenerative diseases not linked to the ageing process (e.g. diabetes related). Neuronal cancers. Potential for establishing the scientific basis for novel therapies for treatment of neurodegenerative diseases and neuronal-linked cancers.
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69364 LYON
Frankreich