Project Objectives
- Identify genes that promote colorectal cancer (CRC) cell invasion using a Drosophila gut cancer model.
- Screen candidate genes from human metastatic CRC for invasive activity in fruit flies.
- Conduct a genome‑wide deficiency screen (~92% of the Drosophila genome).
- Validate candidate genes through targeted assays and functional characterisation.
3Rs Impact
- Replacement of large numbers of mice with Drosophila models for metastasis research.
- Reduction in vertebrate animal use by enabling rapid, high‑throughput genetic screening in fruit flies.
- Improved ability to model tumour invasion without inducing high‑severity burdens associated with CRC mouse models.
- Generation of data that supports future refinement of animal models by clarifying which genes warrant focused study in mammals.
BACKGROUND
Colorectal cancer (CRC) is a cancer of the colon and the rectum. It is the third most prevalent cancer worldwide and the fourth most common cause of cancer-related deaths. If the cancer is localised, the five-year survival rate is 90%, but if the cancer has spread – metastasized – the five-year survival rate drops to 14%. It is therefore crucial to understand how CRC cells adopt a metastatic fate.
Traditional approaches rely heavily on mouse models to study tumour progression, but these models are limited: often failing to develop fully metastatic disease, and requiring very large numbers of animals, many of which experience moderate to severe suffering. However, recent advances in Drosophila research have shown that the fruit fly intestine can effectively model key aspects of CRC biology. Around three‑quarters of human disease‑related genes have fruit fly equivalents, and researchers have successfully engineered a Drosophila system that mimics the molecular drivers of metastatic CRC. These innovations allow researchers to perform comprehensive genetic screens rapidly and humanely.
This project builds on these advances by using the Drosophila adult gut to identify genes that may promote the early steps of metastasis. By screening candidate genes and validating their effects in a refined, high‑throughput system, the project generates insights into tumour invasion while reducing reliance on vertebrate models.
