The eukaryotic genome contains two categories of information: genetic and epigenetic. While the genetic information (DNA sequence) provides the blueprint for the production of components creating a living cell, the epigenetic information layered upon it dictates how, when and where the genetic information should be expressed in developing organisms. Chromatin insulators are specialized DNA elements that lie in the heart of epigenetic regulation. Insulators set up boundaries between the genes on the chromosomes and are believed to act as a neutral barrier to prevent interfering influences from the neighbouring genes. Despite the emerging realization that chromatin insulators are important regulators of expression domains and networks, very little is known about the molecular mechanisms underlying their function. Our recent observations suggest, that the process of poly(ADP-ribosyl)ation, or generation of modifying groups of an ADP-ribose polymer on proteins, could be one of the possible mechanisms regulating the function of insulators. We have demonstrated that one of the proteins, called CTCF, which is involved in the regulation of insulators, can also be modified by poly(ADP-ribosyl)ation. The main aim of the proposed study is to investigate these findings further by providing biochemical and functional data demonstrating how poly(ADP-ribosyl)ation can control vertebrate insulators via CTCF or also perhaps other proteins. As studies of the mechanisms of chromatin insulation are directly relevant to an understanding of mechanisms of regulation of gene expression, the proposed project will also lead to better understanding of many human genetic disorders, including cancer. The results of the work will be disseminated through usual routes (journal and conference publications). In addition, regular meetings are held together with the Essex Rivers NHS Trust to disseminate the results across a broad group of clinicians. My undergraduate and post-graduate academic teaching responsibilities also present an ideal opportunity to communicate the information across the Department and wider. Open Days and Science Days that are regularly held in the University provide another chance to disseminate my science to the younger audience (School children, college students etc). I also have good working relation with the local press (Evening Gazette, Colchester and Wywern, University of Essex) which cover our scientific findings, achievements and events. I also have written several popular science articles to publicize my research. Over the years I have given a number of external lectures to various audiences (general, medical, industrial etc) and am committed to communicating my science to the public in the future.