PhD: Haem Sensing by the Circadian Clock

A fully funded four-year BBSRC MIBTP PhD at the University of Leicester, investigating how haem switches the core clock protein PERIOD on and off – with implications for the body clock, sleep, ageing and neurodegeneration. Open to UK and international applicants. See more funded PhDs.

Supervisors: Prof Andrew Hudson, Dr Hanna Kwon
Department: Department of Chemistry, University of Leicester
Funding: Competition Funded PhD Project (Students Worldwide)

About the Project

Haem is a small organo-transition-metal compound that plays a crucial role in various aspects of cellular biology. Traditionally, its function was thought to be limited to haemoproteins, where it serves as a tightly bound prosthetic group. However, emerging evidence has significantly expanded this perspective. Recent studies highlight a broader and more complex range of biological processes in which haem is used transiently to modulate the activity or behaviour of other proteins.

Our research will focus on PERIOD, a protein that is essential for maintaining the 24-hour rhythm of the biological clock. PERIOD can bind haem at both its N-terminal and C-terminal domains, but the functional significance of this interaction in circadian regulation remains unclear. We hypothesise that haem binding induces a substantial conformational change in PERIOD, which in turn affects its ability to interact with other core clock proteins.

The primary objectives of this research are to characterise the interaction between haem and the PERIOD protein, and to determine the resulting conformational changes in PERIOD’s structure. Since PERIOD’s activity depends on its ability to form a heterodimer with the protein CRYPTOCHROME, we will also investigate how haem influences this critical protein-protein interaction.

The experimental approach will involve biophysical analyses of haem binding to PERIOD using isothermal titration calorimetry and spectroscopic techniques. In addition, we will characterise the structure and conformational dynamics of PERIOD through nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), optical plasmonic nanotweezers, and small-angle X-ray scattering (SAXS).

By elucidating how haem modulates the function of a core circadian protein, this research aims to reveal a broader regulatory role for haem—extending beyond circadian timekeeping to processes such as immune function, neurodegeneration, aging, gas sensing, and ion-channel gating.

Techniques that will be undertaken during the project

The PhD will gain experience in a number of different quantitative techniques including nuclear magnetic resonance and electron paramagnetic resonance spectroscopy, plasmonic optical tweezing and small-angle X Ray scattering. They will have hands on experience with the quantitative measurements using major equipment infrastructure and be provided with the necessary support (software and training) to complete the complex analysis of the experimental data. The student will be guided in handling the large data sets that emerge from these types of experiments, and take part in the planning of all the experiments.

• Nuclear magnetic resonance spectroscopy,
• Electron paramagnetic resonance spectroscopy,
• Circular dichroism spectroscopy,
• UV-visible absorption spectroscopy,
• Fluorescence spectroscopy,
• Optical plasmonic nanotweezing,
• Small-angle X-Ray scattering,
• Protein expression and purification.

Enquiries

Project Enquiries to ah242@le.ac.uk

Programme enquiries to mibtp-admin@leicester.ac.uk

To apply please refer to

https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

Funding Notes

All MIBTP students will be provided with a 4 year studentship. This includes: Tuition fees at the UK fee rate*, a tax free stipend which for 2026/7 is £21,805 per year (2027/8 stipend to be confirmed), a travel allowance over years 1-3, a travel/conference budget, a generous consumables budget, use of a laptop for the duration of the programme. The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.