Cel
"Several age-related neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and Huntington’s diseases, are characterized by the formation of pathogenic proteins aggregates in the brain. Although some regulators have been identified, how aggregates form during aging is poorly understood.
Recently, a modifier of aggregation, MOAG-4, was identified as a positive regulator of aggregation in C. elegans models for neurodegenerative diseases. The role of MOAG-4 is evolutionarily conserved in the human orthologs SERF1A and SERF2. MOAG-4/SERF appears to regulate age-related proteotoxicity through a previously unexplored pathway. Therefore, how this regulator works and in which pathway it acts needs to be established. In this proposal I focus on identifying proteins that physically interact and cooperate with MOAG-4 to drive protein aggregation.
To this end, I will express in worms that lack MOAG-4 a tagged version of MOAG-4 to co-purify MOAG-4 interacting proteins. I will use different proteomic approaches to identify putative substrates and proteins that may form functional complexes with MOAG-4. These interactions will be confirmed in vitro and in vivo. In addition, I will study the proteotoxicity phenotype in mutant worms that are impaired in the expression of these proteins. I will also analyze the protein aggregation process by monitoring aggregate formation in a test tube with purified proteins.
The results of this project will reveal the mechanism by which MOAG-4 acts, and this will contribute to our understanding of how cells cope with toxic, aggregation-prone proteins during aging. Furthermore, new options will be opened for the development of therapeutic strategies to treat human neurodegenerative diseases."
Dziedzina nauki
Temat(-y)
Zaproszenie do składania wniosków
FP7-PEOPLE-2012-IEF
Zobacz inne projekty w ramach tego zaproszenia
System finansowania
MC-IEF - Intra-European Fellowships (IEF)Koordynator
9713 GZ Groningen
Niderlandy