Proteostasis in Aging and Disease (Janine Kirstein)

Research Overview

Our research goal is to advance our understanding of the mechanisms to maintain a functional proteome during the lifespan of a metazoan. We use a model organism that has a long-standing history as an excellent genetic model and more recently cell biology tools became available. However, any biochemical or biophysical studies were few and far in between in the literature of C. elegans research. On the other hand our understanding of chaperones and proteolytic machines, how they work, how they recognize a substrate and contribute to protein folding, are almost entirely based on in vitro or ex vivo data. Our research approach will bridge this gap and provide with C. elegans an excellent model utilizing biochemical, cell biology and genetic techniques addressing important biological questions on the management of protein misfolding and aggregation in a metazoan in vivo.

Specifically, we employ novel proteostasis sensors to analyze the chaperone and proteolytic capacity of distinct tissues and the whole organism during development and aging and upon chronic stress conditions in vivo in real-time. This extensive analysis will allow for an identification of the key chaperone and proteolytic complexes maintaining protein quality control and their interplay upon imbalance of proteostasis during aging and in neurodegenerative disease models (Huntington’s disease, Alzheimer’s disease, Parkinson’s disease etc.).

Our research will use a variety of complementary model systems. In addition to C. elegans we will also utilize mammalian cell tissue culture models as well as biochemical and biophysical in vitro techniques to gain mechanistic insight into the proteostasis network maintaining a healthy and functional proteome.

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)

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