Using photoactive compounds (LightOx) and the inverted Kronoscan system to develop a fluorescence lifetime-based diagnostic and therapeutic tool for cancer and to further the understanding of photodynamic therapy
Used fluorescence microscopy to relate chemical structure of fluorescent compounds to their sub-cellular localisation within cells.
Developed a fluorescence microscopy analysis technique to detect local changes in intracellular ROS production and the subsequent implications upon mitochondria and the local microenvironment.
Characterised the photo-physical properties of photoactivatable drugs, including quantum yield, fluorescence lifetime and two-photon cross sections and related the measured values to chemical structure.
Using the KronoScan fluorescence lifetime system in Edinburgh to see if the HDACi-conjugated photo-activatable drugs can be used as a diagnostic technique. This includes measuring the lifetime of the probes in solution in the presence and absence of HDAC proteins, measuring the lifetime in WT and HDAC-KO cells line, measuring the lifetime in matched cancer and non-cancer cells lines and finally in biopsied tissue.
Publications
Hughes, J.G., Chisholm, D.R., Whiting, A. Girkin, J.M. and Ambler, C.A., 2022. Bullseye Analysis: A Fluorescence Microscopy technique to detect local changes in intracellular reactive oxygen species (ROS) production. Microscopy and Microanalysis. ACCEPTED NOV2022, AWAITING PUBLICATION.
Chisholm, D.R., Hughes, J.G., Blacker, T.S., Humann, R., Adams, C., Callaghan, D., Pujol, A., Lembicz, N.K., Bain, A.J., Girkin, J.M. and Ambler, C.A., 2020. Cellular localisation of structurally diverse diphenylacetylene fluorophores. Organic & Biomolecular Chemistry, 18(45), pp.9231-9245. DOI: https://doi.org/10.1039/D0OB01153C
I studied Physics and Biology as an undergraduate, and I wanted to find a way to bring these two fields together. There aren’t many projects out there that span these two disciplines, but Proteus does, and it gives me the chance to study and learn in both fields. The annual global meeting is great opportunity to present my work and speak with my peers and senior researchers gaining insight from their expertise.
Conferences
Photodynamic Therapy and Photodiagnosis 2022 Nancy
Talk: LXD191 is a novel, triple-action photosensitiser-histone deacetylase targeting inhibitor drug-drug conjugate: efficient and selective killing of human oral cancer cells and animal tissue upon irradiation
Poster: Bullseye Analysis: A Fluorescence Microscopy technique to detect local changes in intracellular reactive oxygen species (ROS) production
Award: Best Poster Communication
Microscopy and Microanalysis 2020 Milwaukee (Virtual Meeting)
Poster: Using FRAP as a technique to quantify local reactive oxygen species (ROS) production