This project aims at understanding one of the key phenomena underlying cellular degeneracy, namely protein aggregation related aging of Escherichia coli bacterium. The experimental system at hand, the E. coli is not only the best-known organism for which all molecular and genetic tools exist but also the simplest aging model available. The well-supported hypothesis we pursue is that aging is a fundamental universal process of all living organisms down to bacteria; as detailed below, we have recently demonstrated that E. coli ages through a process that is largely linked to accumulation of damaged, aggregated proteins.
The process of protein aggregation in vivo will be quantified experimentally and will be related to a diffusion-based modeling approach. Furthermore, the dynamic changes with time of the machinery governing protein quality is considered here as a paradigm of aging and is addressed experimentally. The main features of cellular degeneration, namely, the non-linear increase of damage and the presence of amplifying feedback loops within the cell are addressed by modeling the underlying machinery interactions.
In essence, using both experimental and theoretical approaches, this project tackles the temporal dynamics of in vivo protein aggregation at two scales: (i) the aggregation process per
se and, (ii) the genetic proteostasis network governing the process.