Background and context of the project results.
Epigenetic marks regulate DNA availability for transcription, and accessibility for chromatin, and are as such critical in regulating gene expression, and allow cells to differentiate and respond to environmental stimuli. The importance of these epigenetic marks in inflammation and cancer is evident, and molecules have been newly developed to intervene with these marks (Nicodeme et al, Nature 2011; Kruidenier et al, Nature 2012; Ntziachristos et al, Nature 2014). Such compounds turn out to have extremely anti-inflammatory effects in macrophages, dendritic cells and monocytes, as well as in their target cells (Nicodeme et al, Nature 2010; Kruidenier et al, Nature 2012). Epigenetic mechanisms fundamentally control cell function in health and disease, for instance in cells dividing and their potential to remain self-renewable. Epigenetic medicines show great promise in cancer clinical trials. In the current project we develop a number of projects to show the efficacy of epigenetic medicines to treat inflammation and inflammatory disease.
In several immune-mediated inflammatory diseases (IMID) inhibitors of epigenetic modifications, such as histone deacetylases, are effective in treating inflammatory gut disorders and juvenile arthritis. However, an incomplete understanding of the contributions of specific epigenetic modifiers to immune cell function, and the poor availability of selective tool compounds that target them, currently restricts further development in the clinic. The private partner GSK has an extensive drug discovery program aimed at intervening in epigenetic modifications. These compounds will allow the consortium to map how epigenetic processes in innate immune cells can be targeted to control IMIDs.
The project.
Epimac is an EU funded Training Network for young researchers, focusing on new medicine development in the area of epigenetics. We do this in unprecedented interaction with the researchers from the pharmaceutical industry partner GlaxoSmithKline. This provides the trained investigators the unique opportunity to be trained in academic and big pharma settings, so they learn the process of basic science, drug development, modelling, and clinical application, within their research.
