Epigenetic marks on the DNA are 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).
In this project we aim to establish the repertoire of epigenetic marks in inflammatory cells, identify the epigenetic landscape in inflammatory cells of the inflamed colon mucosa and intervene with these marks to reduce inflammation in inflammatory bowel disease (IBD) and chronic inflammatory diseases.
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.
We will synergize training facilities between AMC, academic partners, GSK, and the associate partner Eureka Institute course curriculum, ensuring a well-balanced training program within the AMC graduate school, GSK, and the business skills program of GutResearch. The consortium provides complimentary state of the art expertise in pharmaceutical development (GSK), epigenetics (GSK, AMC), myeloid biology (AMC) and drug discovery & development simulation programs (GSK, Eureka). Hence, this project will provide ESRs academic-industrial partnership, and a unique overview of the whole drug development cycle. This will enrich ESRs career perspectives by preparing them for research possibilities in both academic and private sectors.