Nuclear receptors function throughout development and aging as molecular integrators of complex physiological regulations, such as growth, reproduction and metabolism. To translate genetic knowledge from the Human Genome into therapy requires intimate understanding of fundamental regulatory mechanisms. CRESCENDO will build on existing knowledge and infrastructures by drawing together European excellence to focus on signalling dynamics, integration of target gene responses during development and aging, and human genetics and pathophysiology, emphasising key nuclear receptors. State-of-the-art genomic and post-genomic techniques will lever advances on mechanisms and kinetics of nuclear receptor signalling in processes underlying development and aging. Information on spatial and temporal aspects of signalling dynamics will feed into a broader vision of how nuclear receptors integrate multiple inputs in whole organisms across the life span. Focus will be on developmental targets, on brain development and aging, and the complex interplay between metabolism, particularly glucose and lipid signalling, and brain function. The brain is emphasised, as its disorders often cause most distress in unhealthy aging. A strong investment in bioinformatics will facilitate data extraction from multi-level analyses (genes to cells to organisms) and accelerate determination of targets, regulatory networks and integration of physiological responses within individuals and populations. The consortium includes molecular and developmental biologists, physiologists and human geneticists, and has access to major national and transnational data banks and resources. Nuclear receptor research is being revolutionised by the combination of technological advances with novel insights into signalling processes. CRESCENDO will ensure that European research in the field accelerates its momentum, fulfilling its potential to catalyse therapeutic innovation and to create substantial socio-economic benefit.
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