Dr. Della David

What causes organisms to age and how does this influence age-related disease such as neurodegeneration? Which mechanisms prevent protein dysfunction with age?

Protein aggregation is a major hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s as well as systemic amyloidosis. In these disorders, specific proteins accumulate and assembly together forming insoluble structures. Small intermediate aggregates formed during the aggregation process are particularly toxic to the organism (Walsh et al., 2002).

In young healthy animals, protein homeostasis is tightly regulated to prevent the accumulation of damaged proteins. However, this regulation is disrupted with age.  Indeed, we discovered that several hundred “normal” proteins are prone to aggregate with age in the absence of disease in the roundworm Caenorhabditis elegans.

Currently, we aim to:

• determine how physiological protein aggregation impacts the health of the organism during aging and in the context of disease
• identify which factors trigger physiological protein aggregation
• discover how we can help the organism protect itself against protein aggregation.

The model organism C. elegans is ideally suited to answer these questions: It has a short-lifespan and characteristic features of aging. Basic molecular mechanisms such as protein-quality-control are well conserved between C. elegans and higher organisms. Additionally, powerful genetic tools are available for C. elegans. In the lab, we use genetic, biochemical and cellular approaches including fluorescent and confocal microscopy as well as mass spectrometry.

Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, et al. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535-539.