Cells possess mechanisms which work to block entry into the cell or export foreign small molecules out of the cell. This is generally advantageous for organism survival unless these molecules are antibiotics deployed to remove bacteria from an infection site or chemotherapy drugs used to destroy cancer cells. To better understand these cellular transports mechanisms it would be highly desirable to directly monitor the uptake and clearance of small drug molecules from cells. However, currently we are lacking imaging technologies that can measure the amount of a drug that has entered a cell. Historically, cellular drug uptake has been quantified by bursting (lysing) cells and measuring drug levels in the remaining solution, typically using spectroscopic methods. Although this approach has provided important insights it is restricted to the analysis of large cell populations. The focus of this PhD studentship is to develop a spectroscopic method to quantify drug uptake in single living cells.
This project will use a method termed Cavity-Reflection-Enhanced Light-Absorption. Cavity-Reflection-Enhanced Light-Absorption uses semi-transparent mirrors to circulate light multiple times through a sample so that the light absorption can be greatly enhanced. Given that the size of a single cell ranges from 0.5 microns (bacteria) to about 10 microns (cancer cells) this enhancement is needed to sensitively detect small light absorption changes associated with drug intake in an otherwise transparent intracellular environment. The PhD student conducting this project will be involved in building and optimizing a miniaturized single cell reflection enhanced spectrometer with a miniaturized detection chamber that can hold a single cell. The student will also be involved in quantifying antibiotic uptake in bacteria focusing on specific Escherichia Coli strains that are particularly virulent due to their ability to clear themselves of antibiotics. The successful student will have a degree in physics, applied physics, biophysics or a related subject. Prior research experience is desirable but not essential.
This award provides annual funding to cover UK/EU tuition fees and a tax-free stipend. For students who pay UK/EU tuition fees the award will cover the tuition fees in full, plus at least £15,009 per year tax-free stipend. Students who pay international tuition fees are eligible to apply, but should note that the award will only provide payment for part of the international tuition fee and no stipend. The studentship will be awarded on the basis of merit for 3 years of full-time study to commence in September 2019.