Measuring drug uptake and engagement in single cells to determine drug susceptibility

My experience of mass spectrometry extends back to my Master's degree where I worked on developing a novel lipid analysis technique. The project investigated the viability of surface extraction analysis technology paired with ESI-MS to interrogate cell wall lipid composition of M. Smegmatis in several antibiotic backgrounds in situ. Very little preliminary work had gone into implementing this technique in the context of lipidomics, leaving the technique to be heavily optimized. Such a project required an open mind to begin navigating the novel format and its caveats. Meticulous investigation into lipid extraction methods and developing knowledge of solvent miscibility through the literature were necessary to make progress. Elements of success I found in developing the solvent systems for lipid extraction- employing toluene to extract a broader range- contributed to the institution continuing this line of research with results that inform ongoing studies.

Stemming from my experiences, both microfluidics and using MS to study heterogeneity of metabolite and tissue have become of great interest. As I became immersed with the LESA-MS technique and read into the literature I became fascinated with its ability to map drug and metabolite distribution and spatially profile proteins all from the tissue surface. Whilst current work developing immunoassays on the MS platform drew my attention to the advent of microfluidic chips interfaced with MS, a proteomic tool evading many labours of the immunoassay. This streamlining of the clinician's and my own approach has inspired a want to apply similar techniques to my current and future works. With the attitude, experience and skills I have built this position is an opportunity for me to learn a great deal and be a genuine asset to the project at multiple levels.