Epigenetic programming of inflammatory memory in endothelial cells - a role in atherosclerosis

Summary In this project we apply a multi-omics approach to study inflammatory memory in purified human umbilical vein endothelial cells (HUVECs) and other human endothelial cell populations. This is an advanced laboratory-based project anticipated to lead to publications.

Project Details

For decades it has been clear that cells of the adaptive immune system are capable of developing long term memory to specific antigens. Contrary to prevailing dogma, more recent data have shown that innate immune cells, such as monocytes and macrophages, may also develop a non-specific memory in response to inflammatory signals. This is known as 'innate immune memory' or 'inflammatory memory' and governs the cell's future response to a range of pathogens. This process can be modelled in vitro, using yeast and bacterial antigens and a range of other stimuli including metabolites and vaccines. Intriguingly, it is becoming clear that inflammatory memory may not restricted to cells of the hematopoietic lineage. Indeed, limited experiments in mouse epithelial stem cells and human endothelial cells indicate a possible widespread phenomenon in response to inflammatory antigens. The establishment and maintenance of this memory is wired in the epigenome of the cell.   Epigenetics' (literally 'above DNA') refers to the study of molecular interactions that influence chromosome structure and gene activity. A key property of many epigenetic marks is that they not only indicate the state of the cell at a set point in time, but can also carry 'memories' of past exposures, with the potential influence cellular responses to future stimuli. Therefore, the epigenome (the complete epigenetic profile of a cell) contains information about the 'past, present, and future' of a cell or tissue.   In this project we apply a multi-omics approach to study inflammatory memory in purified human umbilical vein endothelial cells (HUVECs) and other human endothelial cell populations. This is an advanced laboratory-based project anticipated to lead to publications. It will involve cell culture, DNA/RNA extraction, chromatin immunoprecipitation and sequencing (ChIP-seq), RNA sequencing (RNA-seq) and bioinformatic analysis.