Project: Identification of novel dietary chromatin-modifying using molecular dynamic simulations
Chemical modification of histones represents an important epigenetic mechanism critical for DNA metabolism including, transcription, replication and repair. A well-known example is maintenance of histone acetylation status by the opposing actions of histone acetyltransferase and histone deacetylase enzymes (HDACi) which add and remove acetyl groups on lysine residues on histone tails, respectively. Although numerous compounds have been developed to specifically alter the function of chromatin modifying enzymes (for example, histone deacetylase inhibitors are relatively well-investigated), we are only at the early stages of understanding the long-term epigenetic effects of dietary biomolecules. In this project the student will utilise in silico molecular modelling approaches combined with known experimental affinities for controls, to identify potential dietary chromatin modifying compounds. Acetate and sodium butyrate, which are well known dietary HDACi will be used as starting points for simulations. The student will have access to all of the software (including, Autodock Vina in PyRx, Swissdock and Hex-Server) and expert tuition to complete the relevant simulations. This project will mainly be undertaken at the Alfred Centre, AMREP.
The Karagiannis group aims to understand the role of dietary antioxidants and chromatin modifying compounds on the genome and epigenome in health and disease. They develop predictive models of wound severity and potential for repair in the context of diabetic foot ulcers. This research direction also involves the development of new potential therapeutics.