11.30 Thao Le: Aptamers for live cell imaging
11.45 Amaia Uriz Huarte: Novel small molecules for NK cell based immunotherapy via E4bp4 regulation
12.00 Main Visiting Speaker – Professor Alison Hulme: Real-time, Bioorthogonal Imaging of Intracellular Drug Concentrations
Abstract
A large proportion of the compounds which enter clinical trials never make it to patients. So there is an urgent need to enhance our understanding of the interplay between small molecules, either from nature or designed in the laboratory, and the intricate network of cellular machinery for which they are intended. Integrating advanced imaging techniques into the early stages of drug-discovery campaigns may help to improve pre-clinical modelling studies and reduce the high attrition rates of clinical drug candidates. Stimulated Raman scattering (SRS) microscopy is a new imaging technique which can be used to detect specific chemical bonds within either the small molecule, or the cell, to give high contrast, label-free imaging and to provide intracellular quantification of small molecules.[1,2] In this lecture, recent advances from our group will be discussed including: the design of synthetic Raman-active labels which exploit spectroscopically bioorthogonal functional groups; the use of both dual-colour SRS and multi-modal imaging to probe intracellular drug distribution and drug resistance mechanisms; and analysis of the quantitative data which SRS imaging provides to allow the kinetics of bioorthogonal reactions to be studied in the intracellular environment itself.
[1] ‘Imaging Drug Uptake by Bioorthogonal Stimulated Raman Scattering Microscopy’: W. J. Tipping, M. Lee, V. G. Brunton, A. N. Hulme, Chem. Sci., 2017, 8, 5606-5615.
[2] ‘Stimulated Raman Scattering Microscopy: An Emerging Tool for Drug Discovery’: W. J. Tipping, M. Lee, A. Serrels, V. G. Brunton, A. N. Hulme, Chem. Soc. Rev., 2016, 45, 2075-2089.
Biography
Prof Alison Hulme gained both her BA Hons in Natural Sciences and her PhD in Synthetic Organic Chemistry from the University of Cambridge. After completing postdoctoral work at Colorado State University, USA and returning to the UK to hold a College Fellowship at the University of Cambridge, she joined the academic staff at the University of Edinburgh in 1995. She was promoted from lecturer to senior lecturer, before taking up her Chair in 2017. Her research interests include the synthesis of bioactive natural products, bioorthogonal chemistry, and intracellular imaging. She collaborates with academic and industrial partners in the application of chemical tools to the fields of cancer, Parkinson’s disease, atherosclerosis and multiple sclerosis. Alison is President of the Organic Division Council of the Royal Society of Chemistry (2016–2019).