The role of calcium signalling in regulating of tumour cell behaviour

About the Project

Metastasis is the major cause of mortality in human cancers, yet we know relatively little of the fundamental biology that underlies the important transition to invasive malignancy. This project offers a PhD student the exciting opportunity to use the fruit fly (Drosophila melanogaster) to integrate sophisticated genetic, optogenetic, and imaging techniques to further our understanding of tumourigenesis, tumour progression and invasion. Significantly, this is one of the few model systems in which it is possible to characterise the precise molecular and cellular biological events that lead to the development of a malignant tumour.

Nearly 75% of human disease-causing genes have a functional homologue in the fly and many fundamental cell biological and physiological processes are highly conserved. This has led to the fly being increasingly used as a model to study human cancer. In particular, the Drosophila system we have developed will allow us to investigate the fundamental mechanisms that underly specific tumour behaviours (e.g., multilayering, invasion, survival) and identify novel genes that are relevant to human disease, which will act as potential targets for therapeutic intervention.

Calcium is a universal second messenger implicated in multiple cell functions across all kingdoms of life. In particular calcium signalling is a crucial regulator of processes associated with tumour progression. Despite its importance, our understanding of calcium spatiotemporal dynamics, which determine its functions and switch from physiology and pathology, is limited.

We have the ability to generate and visualise tumours with specific behaviours, in the living fly, through the introduction of distinct genetic lesions. We are additionally able to visualise with spatial and temporal accuracy calcium signalling within these tumourigenic cells. In this project the student will use this system to improve our understanding of the highly conserved molecular machinery underlying changes to tumour behaviour that lead toward malignancy.

This project offers the student a fantastic opportunity to learn state-of-the-art techniques, including:

• Sophisticated fly genetics
• Live high-resolution imaging using confocal and light-sheet microscopy
• Fly pupal mounting and dissections
• Immunohistochemistry
• Advanced optogenetic techniques
• Use of specialised imaging software
• A wide variety of molecular biology techniques
• Data analysis
• Statistical analysis and numeracy skills