Dr. Rachel Simmonds

Co-Director, Member

(SBM, Buruli ulcer and other disfiguring skin NTDs)

Research in my lab focuses on the mechanism of action of the lipid-like exotoxin (mycolactone) made by Mycobacterium ulcerans and the main virulence factor for Buruli ulcer. BU is a disfiguring neglected tropical disease of the skin that affects some of the poorest communities in the world. It causes massive debilitating skin ulcers, often leading to disfigurement or amputation (see http://www.who.int/buruli/en/).

In 2014 we solved the decades-long mystery of its molecular target by showing that it is a broad-span inhibitor of Sec61-dependent protein translocation. The Sec61 translocon is the main entry mechanism for proteins into the ER, and mycolactone stops further production of secretory and type I/II transmembrane protein production due to their mislocalisation and subsequent degradation.
We are now applying this knowledge to understand the pathogenesis of Buruli ulcer with a current focus on cellular stress and the interaction between the immune and haemostatic (regulation of blood clotting) pathways. In addition, our research is also starting to reveal further secrets of the still incompletely understood molecular mechanisms of translocation into the ER.

My background is a degree in Molecular Biology (University of Manchester) and a PhD from Imperial College (David Lane). My early post-doctoral work at Imperial College focussed on haemostasis, endothelial cell biology and genotype/phenotype interactions in thrombophillic conditions. I later joined the Macrophage Biology group at the Kennedy Institute of Rheumatology (Imperial College London), to study inflammatory signalling and post-transcriptional gene regulation (studying mycolactone and miRNAs). I was appointed to the University of Surrey in 2011, after receiving my first award from the Wellcome Trust. I currently hold a Wellcome Trust Investigator Award in Science.

Since her first visit to Ghana in 2015, where she saw the impact of Buruli lesions first-hand, the work of the group has expanded to wider interdisciplinary work encompassing the role of blood coagulation in the pathogenesis of the disease, diagnosis and transmission.