Label-free Raman Imaging for Investigating Drug Localisation Inside Cells

A key challenge within the drug discovery process is to understand how compounds behave and interact with molecules in a cellular system. Additionally very little is known of the free fraction, location and interaction of drugs with organelles inside cells. The available techniques either involve cell rupture or labelling, that is, they are either destructive to cells and therefore no location information can be extracted or they are invasive (if fluorophores are used) or lack the resolution (if radio labels are used). Surface-enhanced Raman spectroscopy (SERS) is a widely established optical, highly sensitive, label-free, chemically specific, molecular finger-printing technique and offers an interesting potential solution. SERS relies on the ability of nanoscale materials to enhance the otherwise weak vibrational signals in Raman spectroscopy. In our group we have recently shown that using targeted nanoparticles as SERS probes the biochemical changes inside cells and their nucleus can be monitored [Nano Letters 2013 13(6) 2463-2470]. This strategy will be developed and improved to explore the value it can add to the drug discovery process. The broad aim of the project is to develop the applications of chemically selective techniques such as surface-enhanced Raman spectroscopy (or related imaging techniques) to give novel/better detection/cell-based assays and improve our understanding of localisation of drugs and their interactions inside cells.
In this collaborative project the student will learn and develop spectroscopic and microscopic imaging techniques, wet chemical and analytical techniques, cell based assays and image analysis as applied to biomedical approaches.