Final Activity Report Summary - NUCSYS (Systems biology of nuclear receptors: A nutrigenomics approach to aging-related disesases) Complex organisms such as human beings are made up of tens of trillions of individual cells, which represent quite a complicated set up, by any standard. When communication between these various parts fails, a system-wide breakdown can follow. The academic and industrial partners within the NUCSYS research training network (RTN) set themselves the task of understanding how to avoid such a scenario. The network included leading academic and industrial partners from nine European Union countries. Its success provided clear evidence of the importance of cooperation and exchange between all of those working in the wider medical research community. Cells perceived and responded to their environment. They triggered physical development, enabled wounds to heal and kick-started the immune system into action when the body eds under attack from a virus. NUCSYS sought to understand the influence of nutrients contained in the food we eat on the behaviour of cells in the human body. The starting point for the project was one of the key players in inter-cellular communication, i.e. nuclear receptors. These could be found within the cells that mediated the activity of hormones and other substances, including certain vitamins. Nuclear receptors constituted a large network in the human body. They sensed lipids, carbohydrates and cholesterol compounds and assessed overall energetic status. They also prompted a multitude of responses. Nuclear receptors, in concert with other proteins, regulated how genes worked. They triggered cell growth, changes in metabolic rate and homeostasis, among other things. As with many physiological processes, the ways in which the genes responded were subtle, affected by other biological functions and given conditions. But when disease stroked, the normal working relationship between the sensors and the response networks was disrupted. A better understanding of these processes could lead to novel insights into how to improve health. NUCSYS aimed to bring together a diverse range of data on their activities, ultimately generating a unified paradigm capable of describing and predicting complex processes in living cells and organisms. The next steps would be to describe gene and nutrient interactions mathematically and model the impact of diet on health and the development of disease. Eventually this would help doctors to treat diseases more effectively. The power to predict first requires the integration and interpretation of large amounts of data from '-omics' based studies, i.e. genomics, transcriptomics, proteomics, metabolomics and physiomics. The NUCSYS consortium comprised 14 academic and two active industrial partners and brought together researchers from disciplines that had not traditionally sat side by side. Molecular, cellular and developmental biologists, pharmacologists, physiologists, systems mathematicians and bio-informaticians were all working together, with the same goal in their sights.
