The long-term goal of our research group is to understand how the architecture of the genome impacts gene expression. We develop our own technologies, combining molecular biology and bioinformatics to study how the genomic context (chromatin, sequence at a large scale, local conformation of the genome) influences gene regulation. This method, called Thousands of Reporters Integrated in Parallel (TRIP) allows us to measure the expression of a reporter inserted at different locations of a target genome. The position accounts for large variations of gene expression in Drosophila. The large number of integrations obtained by TRIP allows us to investigate the underlying causes of position effects. Surprisingly, the major player does not seem to be chromatin, as we expected. Instead, the greatest influence on position effects seems to come from interactions between genes. We are also using TRIP in the clinical context of HIV infections. The expression of proviruses depends on the insertion site, as HIV seems to hijack the nearby enhancers. As a consequence, proviruses inserted far from active genes and enhancers are more likely to become latent and re-infect the patients later in their life.
- Develop the TRIP technology
- Understand position effects in Drosophila
- Understand latency in HIV