CHROMATIN PLASTICITY · Chromatin structure and plasticity

Final Activity Report Summary - CHROMATIN PLASTICITY (Chromatin Structure and Plasticity)

Chromatin is the cellular structure that packages our genome. This is carried out by a range of proteins that continuously regulate the accessibility of the DNA template to all types of cellular machineries required for cellular function. On the one hand chromatin thus ensures the stability of our genome, on the other hand it is the plasticity through which it is dynamically remodelled that governs differences in cell fate decision during development, as well as a the regulation of gene expression depending on external stimuli. Further, since many human diseases affect the unravelling of chromatin structure or the interpretation of the genetic code, basic and translational research in the study of chromatin plasticity offers the opportunity to open up new frontiers in the field of biomedicine and in the search for novel therapeutic solutions. The aims of our Marie Curie Research Training Network was to systematically investigate many complementary aspects of chromatin and gene regulation plasticity, such as the structure and function of distinct chromatin types, the role of specific chromatin modifications and histone variants, nuclear architecture, recombination, alternative splicing and post-transcriptional forms of gene regulation, such as the mechanism and pharmacological manipulation of microRNA-mediated pathways. The research spanned many inter-disciplinary methodological approaches, with a strong focus on from structural biology, developmental biology, genomics and bioinformatics. During the four years of this project, our consortium has identified and dissected the role of novel factors playing a role in heterochromatin formation, including the identification of a link to premature aging. Several groups have focused on the regulation of the lymphocyte development and human leukaemia finding for example that DNA damage influences the differentiation of lymphocytes. Some key gene regulatory factors, such as the growth factor independence 1 (Gfi1), have been shown to play role in this process. Further, microRNAs are fundamental in the epigenetic regulation of leukaemia and initial results show a high therapeutic potential of small molecule compounds that deregulate the function of specific microRNAs. Our large Network brought together 12 research groups from 9 different countries and over its duration supported 35 young researchers from 15 European and non-European countries. Fundamental to the success of our Marie Curie Network was thus that we developed and implemented an extensive training program where young researchers could come together as a community and to receive state-of-the-art training on emerging fields, such as high throughput sequencing technology, as well as in complementary skills, such as writing, presentation, management and team communication skills. Further, they had access to many other career development opportunities, such as exchanges, visits, participation to conferences, discussions with their external Network Mentor, extensive networking (at events such as the Spetses Summer School, in particular) and a day focused on exploring future careers and their career advancement. We therefore believe we made our contribution to helping to prepare a new generation of competitive, talented, open-minded and communicative young scientists.

Data: CORDIS, © European Union