Abstract
Understanding the spatial and temporal dynamics of protein functional states is essential for uncovering the processes that contribute to disease progression. This thesis enhances the application of Forster Resonance Energy Transfer resolved by Fluorescence Lifetime Imaging Microscopy to investigate protein functional states and their relationship to protein expression.We employ functional protein analysis in melanoma and clear cell renal cell carcinoma. In stage II melanoma, we assess immune checkpoint interactions before and after immunotherapy within the tumour immune microenvironment. We also examine checkpoint blockade-resistant melanoma in mouse models, focusing on the functional interactions that occur after AXL tyrosine kinase-targeted treatment. Our analysis compares functional state distributions using statistical methods.
We developed FuncOmap, a computational framework to map protein functional states onto protein expression image data, and validated it in clear cell renal cell carcinoma. FuncOmap addresses limitations of conventional statistical analyses and reveals the spatial distribution of functional states among protein pairs at tissue and cellular levels.
This research highlights the potential of integrating spatially resolved functional proteomics with computational analysis to enhance patient stratification, inform therapeutic decisions, and support the development of personalised cancer therapies. The insights gained from functional analysis can facilitate the generation of new hypotheses regarding disease pathways.
| Date of Award | 14 Jan 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Banafshe Larijani (Supervisor), Julian Padget (Supervisor) & Jonathan Du Bois (Supervisor) |
Keywords
- alternative format