PhD Studentship: Developing a new approach to cancer: modelling complex mutational cooperation and competition during tumour progression

Developing a new approach to cancer: modelling complex mutational cooperation and competition during tumour progression

Supervisors:

Prof David Bryant, School of Cancer Sciences
Dr Ke Yuan, School of Computing Science & School of Cancer Sciences
Prof John Le Quesne, School of Cancer Sciences
Prof Owen Sansom, School of Cancer Sciences

Summary:

Tumourigenesis is driven by a complex interplay of genetic mutations, environmental factors, and cellular interactions. Traditional cancer therapies often fail due to the heterogeneous nature of tumours, where not all cells carry the same mutations. This project aims to address this challenge by exploring how different cancer cell subpopulations cooperate or compete to drive tumour evolution and metastasis, using colorectal cancer (CRC) as a model.

The project will develop advanced chimeric tumour models to study these interactions. By employing optical and genetic barcoding techniques, the candidate will track subpopulations in vitro and in vivo, assessing their roles in tumour progression and response to therapies. Key objectives include creating complex mutational models and evaluating how these models evolve under therapeutic pressure.

The project involves a multidisciplinary supervisory team with expertise in live imaging, organoid transplantation, deep-learning histopathology, and multiplexed tissue labelling. The research will provide comprehensive training in cutting-edge techniques, including advanced organoid culture, single-cell sequencing, and multiplexed imaging.

Ultimately, this project aims to enhance tumour modelling and therapeutic strategies, improving cancer treatment outcomes by targeting subpopulation dynamics.

References:
1. Freckmann EC, et al., Nat Commun. 2022.
2. Jackstadt R, et al., Cancer Cell. 2019.
3. Claudio Quiros A, et al., Nat Commun. 2024.
4. Wroblewska A, et al., Cell. 2018.