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Content archived on 2024-06-18

Cell-type-specific modulation of protein homeostasis in health and disease

Objective

The correct folding and assembly of proteins and protein complexes is essential to cellular function. Cells have evolved a network of proteins that detect and correct protein damage to maintain proteome health. However, many protein-misfolding diseases, including Huntington’s and Alzheimer’s diseases, are characterized by the accumulation of damaged proteins with devastating consequences for protein homeostasis (proteostasis), resulting in a collection of deleterious phenotypes and affecting many processes. Given that protein expression is cell-type specific, the proteins affected across different cell types are expected to vary. If this is in fact true, then the protein expression profile of a cell will have a profound impact on the folding capacity of its proteins in health and disease.
The objective of this project is to determine how cellular proteostasis is adjusted in a cell-specific manner. To this end, I will combine several complementary approaches to compare proteostasis network interactions in different cell types of Caenorhabditis elegans. I will begin by using fluorescent sensors that enable a real-time assessment of proteostasis in a living organism to identify sensor interaction with the proteostasis network in muscle cells. I will then perform cross-tissue analyses of sensor interactions with the proteostasis networks in neuronal and intestinal cells. Finally, I will examine how the chronic expression of misfolded proteins influences sensor interactions with the proteostasis network. This approach will allow me to examine how protein interactions with the cellular proteostasis machinery are changed in response to an altered cellular environment and to determine how the resources of proteostasis are distributed in health and disease. I believe that the proposed research will have broad implications for elucidating the dynamics and limitations of the cellular proteostasis network in a living organism, with long-term implications for therapeutics.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2010-RG
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator

BEN-GURION UNIVERSITY OF THE NEGEV
EU contribution
€ 100 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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