Mr Luke A Doughty

My research involves understanding how activation of the hypothalamic-pituitary-adrenal (HPA) axis and glucorcorticoid/mineralocorticoid receptor activity affects the hippocampal epigenome in stressful stimuli. Specifically, I investigate how acute stress influences in vivo nuclear dynamics and genomic topology in the hippocampus in 3-dimensional space. Redistribution of the spatial organisation of chromatin can have rapid and profound effects on genomic architecture and transcriptomic activity across the classical A and B nuclear compartments. As such, alterations in chromatin accessibility and genomic looping events represent physical sub-nuclear phenomena which may in-part be HPA/steroid receptor-mediated. Further, the genome regulatory logic can be heavily influenced by the status of the histone modification landscape and net nucleosomal electrostatic charge distribution across megabase regions. Together, I integrate all of these levels of regulation to gain a comprehensive understanding of stress-related nuclear dynamics.

To understand whether large-scale 3D genomic redistribution occurs at nanometer resolution as a result of acute stress and HPA activity, I use and develop several cutting-edge biophotonic and super-resolution nanoscopic approaches such as: single-molecule localisation microscopy, dSTORM, stimulated-emission-depletion and MINFLUX. I also develop bioimaging analysis tools for single-molecule localisation techniques.