Protein homeostasis in development and aging

Our group is interested in protein homeostasis, or proteostasis, which corresponds to the capacity of cells and organisms to maintain the integrity of their proteome. Loss of proteostasis during aging is a major driver of cellular dysfunction, and many age-related diseases are characterized by pathological protein misfolding and aggregation. Considering the central role of chaperones in proteostasis, and the expansion of the chaperone network during evolution, our research generally aims at unraveling how the diversity of the chaperone network is harnessed to regulate proteostasis and protein phase transitions in various cell types.

Current research in the lab is divided into three projects that aim to:

• Characterize the composition and function of chaperone networks in germ cells, as a tissue with specific requirements for proteostasis and biomolecular condensation.
• Investigate the role of the Hsp70 chaperone network in the dynamics and architecture of stress granules in various tissues and during aging.
• Model the pathological transitions of the ALS-associated protein and stress granule component TDP-43, and their regulation by the chaperone network.

To study this, we are using the Caenorhabditis elegans model system, a short-lived, transparent animal with powerful genetic tools. We combine approaches such as CRISPR/Cas9-mediated fluorescent labeling of endogenous proteins, live imaging, proximity proteomics, reverse genetics, and physiological assays, to gain insights into these processes from the molecular to the organismal level.