Competition Funded PhD Project (Students Worldwide)
About the Project
A fully funded PhD opportunity to participate in the world-leading research undertaken by the EPSRC Doctoral Landscape Award at the University of Sheffield.
Supervised by Prof Ashley Cadby and Dr Joe Tyler.
The University of Sheffield is one of the leading Russell Group universities in the UK. We carry out cutting-edge research with strong links to industry. When you enrol to do a PhD with us, you will be working with world-leading academics and have access to top of the range facilities. As a PhD student you will have the opportunity to gain skills not only to conduct research, but also to take your career to the next level, whether you want to stay in academia, go into industry or the public sector, or set up your own company. You will have access to a range of training and support services to help you excel in your studies and beyond.
Project Description
When immune cells called macrophages swallow invading bacteria, they trap them inside a small membrane-bound compartment and then rapidly acidify it, turning it into a hostile, acidic environment designed to kill the intruder. This drop in acidity is one of the immune system's fastest and most effective weapons. But some pathogens fight back by disrupting or slowing that process, so understanding exactly how they do it depends on being able to measure acidity accurately, inside a single compartment, in a living cell, in real time.
That is harder than it sounds. The usual tools are fluorescent probes: dyes or proteins that change how brightly they glow, or how long they glow for, as acidity shifts. The trouble is that brightness is an unreliable messenger. It fades as the probe bleaches under the microscope, changes with how much probe has built up, and is distorted by the crowded, variable environment inside a cell. So, although these probes are widely used, they cannot easily deliver a true, reliably calibrated reading from a single compartment.
This project takes a different approach, borrowed from quantum sensing. Rather than reading out acidity as a brightness, we will read it out as a frequency, a property that does not care how bright your probe is, how much of it there is, or how long you have been imaging. We will use a sensor protein whose internal electronic structure absorbs microwaves at a frequency that shifts predictably as its immediate chemical surroundings become more acidic. Because that shift is measured as a frequency rather than an intensity, the technique is naturally immune to the artefacts that limit conventional fluorescent probes.
You will help build a custom microscope from the ground up, combining precision light detection, sensitive single-photon counting and microwave delivery into one working instrument: a serious piece of quantum instrumentation and an excellent grounding in optical physics and electronics. Once built you will then use it to calibrate the sensor protein's response across the full range of acidity found in cells, and check that the readout is not thrown off by temperature or salt concentration, the kind of everyday variation any real biological measurement must survive. Finally, they will take the sensor into living macrophages, attach it to the compartment where bacteria are digested, and watch, in real time and in a single organelle, exactly how acidic that environment becomes, benchmarking the new method directly against the dyes currently in use.
This is a rare opportunity to work right across the boundary between physics and biology. Techniques like this have, until recently, mostly needed specialised low-temperature equipment; it is only in the last few years that sensor proteins working at room temperature have made this kind of quantitative, single-compartment chemical imaging genuinely achievable. The student will graduate with hands-on experience of building optical and microwave instrumentation, of quantitative spectroscopy, and of cell biology and immunology, a combination that is genuinely difficult to get from a single PhD, and one that opens doors into both fundamental quantum sensing research and applied biomedical imaging.
No prior experience of quantum physics or cell biology is required, just curiosity about both, and a willingness to get equally comfortable in the optics lab and at the cell culture bench.
How to apply
Interested candidates are strongly encouraged to contact the project supervisors to discuss your interest in and suitability for the project prior to submitting your application.
Please refer to the EPSRC DLA webpage for detailed information about the EPSRC DLA and how to apply.
Applicants must ensure that they use the correct application form linked to the EPSRC DLA webpage and must submit an application for October 2027 entry. The form is unique to the EPSRC DLA. It contains the list of advertised projects from which to select, and three questions specific to the DLA.
The application deadline is 17:00 GMT 13 January 2027.
The majority of our DLA studentships will be allocated to candidates who qualify for Home fee status, in accordance with EPSRC funding regulations which place strict limits on international recruitment.
Funding Notes
The award will fund the full tuition fee and a maintenance stipend at the UKRI rate (currently £21,805 per annum) for 3.5 years, as well as a research grant to support costs associated with the project.