Florian Groelly - ERS 8

Name: Florian Groelly

Nationality:  French

Main Host Institution: Department of Oncology, University of Oxford (UK)

Academic Background:
BSc in biology, University of Basel
MSc in molecular biology, University of Basel

Project title:  Mechanisms for overcoming the G1/S checkpoint in BRCA1/2-deficient cells

Project background:
Human cells contain DNA, which is arranged into chromosomes and encode all information required for cell growth and development. In 1953, Watson and Crick discovered that DNA structure forms a double-helix. Exposure of cells to ionising radiations or ultra-violet light can cause DNA damage, for instance breaks of the DNA double-helix. This damage can have severe consequences for the cell or the whole organisms: it can turn off genes and lead to cancer development. DNA double-strand break is one particularly toxic type of damage; fortunately, eukaryotic cells have evolved several mechanisms to repair broken DNA. One important pathway of DNA repair is homologous recombination.  Different proteins are involved in order to recognize DNA break and to accurately reform the double-helix. The products of BRCA1 and BRCA2 genes are two key players in homologous recombination and therefore they are essential for chromosomal stability.

Loss of BRCA1 or BRCA2 genes predisposes to breast cancer. Moreover, some patients with stomach, ovarian and prostate cancers have non-functional BRCA1 or BRCA2 proteins. Understanding how these proteins work in our cells could help prevent cancer or develop effective cancer treatments for these patients.

Project Aim: Because BRCA1 and BRCA2 are very important for protecting our DNA against damage, their loss causes cell death. My work aims to understand how tumours that lost BRCA1 or BRCA2 are still able to proliferate and to grow. For tumours to grow, each cell has to duplicate its DNA and to divide. These steps are highly regulated and sensitive to DNA damage. We are trying to understand the impact of BRCA1 and BRCA2 on the regulation mechanisms. 

Expected outcome:  We expect that our study will highlight weaknesses of the BRCA1/2-deficient cells and tumours, which could be exploited to design new treatments that specifically eradicate this type of cancer.

Contact: http://www.radiationoncology.ox.ac.uk/research/madalena-tarsounas