Investigating cellular heterogeneity in tendon homeostasis and ageing using cutting-edge single-cell proteomics

About the Project

Tendon injuries commonly end racehorse careers, yet how ageing drives this remains unclear. This project uses novel single-cell proteomics to reveal how distinct tenocyte populations change with age, uncovering mechanisms of tendon degeneration and enabling innovative strategies to preserve tendon strength and equine performance. Tendon injuries are a leading cause of pain, lameness, and early retirement in racehorses, with incidence increasing markedly with age. However, the cellular mechanisms driving tendon ageing remain poorly understood. This project aims to characterise how ageing alters the functional protein landscape of tenocytes, the principal tendon cells which exist as diverse subpopulations. Using cutting-edge single-cell proteomics (SCP), the candidate will investigate cellular heterogeneity within the equine superficial digital flexor tendon and identify age-related changes that contribute to tendon degeneration.

The project has four main objectives: (1) optimise SCP methodologies for equine tendon, including single-cell isolation and sorting; (2) generate high-resolution single-cell and bulk proteomic datasets from young, middle-aged, and aged tendons; (3) apply advanced bioinformatics to identify and characterise distinct tenocyte subpopulations and their age-associated phenotypes, integrating findings with existing single-cell transcriptomic datasets; and (4) validate key findings using immunohistochemistry and spatial localisation techniques. Together, these approaches will provide an unprecedented, functionally relevant understanding of tendon ageing.

The student will undertake interdisciplinary training across molecular biology, proteomics, and computational analysis. They will gain hands-on experience with rare SCP technologies (e.g. CellenONE and mass spectrometry) at the University of Liverpool’s Centre for Proteomics Research, alongside training in bioinformatics, including R, data integration, and pathway analysis. The project includes a 6–8 week placement at the Royal Veterinary College to develop expertise in tissue imaging and validation techniques. The supervisory team provides complementary expertise and strong collaborative links, ensuring exposure to a broad network of researchers and facilities.

The PhD is structured to support progressive skill development. The first year will focus on training, experimental design, and optimisation of protocols. The second year will centre on data acquisition (SCP and bulk proteomics), while the third year will emphasise data integration, validation, and independent analysis. The final phase will be dedicated to completing the thesis and disseminating findings through publications and conferences.

Overall, this project offers a unique opportunity to work with world-leading technologies and address a major problem in equine health, while receiving comprehensive, interdisciplinary training that prepares the candidate for careers in academia, industry, or veterinary research. We have funding for a vet or none vet (UK only) for this PhD.

Supervisors: Prof Mandy Peffers, Prof Ed Emmott, Dr Chavaunne Thorpe