COI Project 5: Lipid specific pathway in malignancy and development of novel therapeutics

About the Project

Targeting T-cell responses represents an emerging strategy for modulating immune responses in cancer. While much of cancer immunology has focused on peptide antigens presented by classical MHC molecules, alternative antigen‑presentation systems are increasingly recognised as important contributors to tumour–immune interactions. Among these, the CD1 family of non‑polymorphic, MHC‑like molecules presents lipid antigens to T cells, offering a distinct and potentially underexplored axis for immune recognition and therapeutic intervention.

Malignant transformation is associated with substantial alterations in cellular metabolism and membrane lipid composition. These changes may influence the repertoire of lipids available for presentation, potentially altering lipid-reactive T‑cell function and contributing to immune evasion. In addition, tumour‑intrinsic and microenvironmental factors may shape antigen presentation and T‑cell activation states, further influencing disease progression and response to therapy. This project aims to explore how tumour‑associated lipid pathway changes influence T‑cell responses, with the goal of identifying new targets for therapeutic benefit.

To address this, the project will incorporate bioinformatic and lipid profiling approaches to define disease‑associated lipid landscapes and their perturbation during malignancy. Integration of in vitro and in vivo cellular and molecular immunology will enable the identification of candidate antigenic lipids, characterisation of CD1‑dependent presentation pathways, and mapping of T‑cell responses linked to these signals in malignancy. These combined approaches will broaden our understanding of how lipid antigen presentation contributes to tumour immunity and how this can be deployed for development of novel therapeutic strategies.

KEY TECHNOLOGY

• Functional T‑cell assays to assess antigen recognition and effector responses
• Human organoid systems and in vivo models to recapitulate tissue and tumour microenvironments
• Multiparameter flow cytometry and high‑dimensional immune profiling
• Mass spectrometry-based characterisation of disease‑associated lipid landscapes

TRAINING OPPORTUNITIES

• Participation in lab meetings, journal clubs, and University‑wide seminars
• Training in experimental immunology, data analysis, study design, and translational approaches.
• Opportunities for manuscript writing and scientific presentation
• Access to the Medical Sciences Division Skills Training Programme