Cutting to the Core: Mechanistic Dissection of Nuclear Protease Function in Tumour Biology

About the Project

Proteases are classically viewed as degradative enzymes that function in the cytoplasm or extracellular space. Emerging evidence reveals a surprising role for specific proteases within the nucleus, where they influence key processes such as chromatin remodelling, transcriptional control, and DNA repair. These nuclear proteases represent an uncharted regulatory layer in cancer biology, with the potential to profoundly shape gene expression and tumour cell behaviour.

This PhD project will explore how nuclear proteases contribute to cancer cell proliferation, stress responses, and genomic stability. Using a combination of cell biology, molecular biology, biochemistry, and proteomics, the student will identify protease substrates and interaction networks, and examine how their activity is altered in tumour versus normal cells. Advanced imaging and gene editing will be employed to track protease localisation and function within the nucleus.

By dissecting these mechanisms, the project aims to uncover novel pathways linking nuclear proteolysis to oncogenic transformation, opening new avenues for biomarker discovery and therapeutic targeting.

This project offers interdisciplinary training at the interface of molecular cell biology, cancer research, and protease biochemistry, ideal for students with a passion for uncovering hidden regulatory mechanisms in cancer.

Training that will be provided through the research project

The successful applicant will receive comprehensive, interdisciplinary training across several complementary areas:

1. Molecular and Cell Biology: CRISPR/Cas9 genome editing, transfection, and protein expression analysis.
2. Proteomics and Biochemistry: Protein interaction mapping, substrate identification, and activity-based profiling.
3. Microscopy and Imaging: Confocal and live-cell imaging to track nuclear localisation and dynamics.
4. Cancer Biology: Use of cell line and 3D culture models to assess tumour-relevant phenotypes.
5. Data Analysis and Bioinformatics: Interpretation of proteomic datasets and integration with gene expression data.

Expected impact activities

This project will generate new mechanistic insight into the roles of nuclear proteases in tumour biology, addressing a largely unexplored aspect of cancer cell regulation. The findings have the potential to identify novel biomarkers and therapeutic targets, supporting future development of precision oncology approaches. In addition to advancing fundamental knowledge, the project will promote skills development and research capacity in cutting-edge molecular and proteomic technologies. Impact activities will include publication in high-quality journals, presentation at national/international conferences, and engagement with the wider scientific community through outreach and public engagement events focused on cancer research.

Funding Notes

This project is not funded; applications are welcome from self-funding candidates.

References

Proteases, mechanisms, cell biology, cancer, nucleus, therapeutics