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Gene & Protein Expression

We investigate the molecular mechanisms by which eukaryotic cells survive to adverse circumstances. In particular, we study the unique regulation of the genes activated in response to stress using single-molecule imaging approaches. Our research aims to decipher how cells produce the components of the stress response, the heat shock proteins (HSPs), at the expense of shutting-down specific and general functions. The HSPs are families of molecular chaperones with cytoprotective properties. They recognize denatured proteins, fold them, and prevent their toxic aggregation. Once protein homeostasis is recovered, cells restore their functions and precisely cease the production of HSPs. The success of the stress response relays on the tight and unique regulation of the life-cycle of HSP mRNAs. The unbalanced expression of HSPs leads to a variety of diseases that ranges from cancer to neurodegeneration.

Our goals are:

1. Resolve the execution of the stress response in time and space.

We have developed single-cell and single-molecule fluorescence microscopy technologies to interrogate individual HSP mRNAs about their life-cycle.

2. Define the modulators of the heat shock response.

They will provide the means to treat diseases resulting from the unbalanced expression of HSPs, a hallmark of age-related diseases. To this end, we combine novel imaging tools with molecular, biochemical and genetic approaches.

3. Decipher how evolution has tailored the components of the stress response to overcome new challenges while preserving functionality. We use different model organism, from yeast to primary neuronal cultures, to study how we handle hazard conditions and adapt to live in an environment that is not always optimal.