The objective of this proposal is to facilitate the reintegration of a European researcher currently performing structural biological research in a leading laboratory in the US. The researcher will apply structural biology and biophysical techniques to investigate the molecular bases of mechanisms involved in programmed cell death (apoptosis). Apoptosis is implicated in several human diseases (autoimmunity and neurodegenerative disorders), probably being an initial factor in the onset of cancer, and therefore a target for its treatment. The project aims at filling the existing gaps in the molecular-structural understanding of apoptosis, thus helping towards creating a mechanistic scaffold for the development of new strategies to clinically treat cancer.
This goal will be implemented in four specific objectives:
1.1) identifying the structural and dynamic requirements of protein-protein interactions and complexes between death domains;
1.2) characterizing the aggregation and oligomerization properties of apoptotic proteins;
1.3) investigating the role of minimal death domains;
1.4) analysing the factors responsible for protein membrane translocation and membrane-bound conformations.
These objectives will be tackled with a combination of Nuclear Magnetic Resonance Spectroscopy as the main tool for structure and dynamic information, Atomic Force Microscopy and Multi-Angle Light Scattering for oligomerization studies, and Fluorescence Spectroscopy to obtain information on membrane binding. The added value of this grant lies on counteracting the "brain drain" by facilitating the reintegration to Europe of a promising young researcher in the area of the structural biology of programmed cell death, an area in which US-based research heavily dominates. Additionally, funding this grant will consolidate a female researcher as a fully independent scientist in an area (Nuclear Magnetic Resonance Spectroscopy), in which women are seriously underrepresented.
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