Morgan Brisset

Morgan BrissetResearch Project Title: Characterising the role of netrin-1 and its dependence receptors in drug tolerance and treatment-induced plasticity of metastatic human CRC.

Research Project Summary: Colorectal cancer (CRC) is one of the most common and lethal tumour types worldwide. The ultimate cause of patient fatality is metastases forming in vital organs, such as the liver, and each year metastatic progression leads to a fatal outcome for over 690,000 patients globally.

The recent literature suggests that expression of Epithelial-to-Mesenchymal Transition (EMT) correlates with therapy resistance and that post-treatment residual disease often displays mesenchymal and tumour-initiating features. Interestingly, netrin-1 and its receptors DCC/UNC5B have been shown to be very important in colorectal tumorigenesis and very recent unpublished data support the view that the pair netrin-1/UNC5B is instrumental in regulating tumoral EMT.

Yet, no data currently exist on the implication of netrin-1 and its receptors in the regulation of intra-metastatic heterogeneity and of the pathways metastatic cells can use to resist treatment. Our project aims to shift this roadblock by identifying which metastatic tumour cells drive post-treatment regrowth and by characterising the mechanisms underlying this ability. Taking advantage of the combined expertise of the Australian and French partners, we will characterize the emerging role of the netrin-1/UNC5B axis as a driver of drug tolerance and cancer cell plasticity.

Student Profile: I started my PhD candidature in March 2020 at the University of Melbourne, under a joint collaborative project with the University of Claude Bernard Lyon 1. Before then I studied at the University of Montpellier where I completed a bachelor’s degree in “Biochemistry” and a master’s degree in “Cancer Biology”. During the course of my Master’s degree I had the opportunity to do two internships: one at the “Functional Genomics Institute” of Montpellier where I worked on “Colorectal Cancer Stem Cells”, and another at the “Cancer Research Institute of Montpellier” where I worked on the “impact of apoptotic proteins on liposarcoma metabolism”.

My research will be funded by the Melbourne research scholarship and I thank the University of Melbourne for giving me the opportunity of work on such an interesting project.

In my leisure time (if I have some during my PhD!), I have some hobbies like playing ukulele, doing muscle workout, reading, cooking and cinema. I also hope I will have some time to discover Australia and its culture.

Project Duration: 2020-2023

Supervisors: The University of Melbourne: Professor Frederic Hollande, Dr Melodie Grandin / Université Claude Bernard (Lyon1): Professor Patrick Mehlen

Home University: The University of Melbourne
Partner University: University Claude Bernard Lyon 1