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Identifying and deciphering the mechanism of the cellular machinery responsible for disaggregation of intracellular prion-like Tau aggregates

Objective

Tauopathies are a group of neurodegenerative diseases, the most common of them being Alzheimer’s disease, which are associated with the aggregation of protein Tau in the brain. Despite major research efforts world-wide, the mechanism of Tau aggregation and its pathogenesis giving rise to such neurodegenerative diseases is not yet understood. Therapeutics to cure these tauopathies, including Alzheimer’s disease, are urgently needed. We aim to identify the conditions, the cellular machinery responsible and the mechanism of disaggregation of intracellular prion-like Tau aggregates in HEK293 cell lines, with one condition already been identified (starvation). For identifying the conditions of disaggregation, high resolution confocal microscopy will be used for visualizing intracellular Tau aggregates tagged with yellow fluorescence protein (YFP). For deciphering the cellular components responsible for disaggregation, the proteins associated with the aggregates will be identified using quantitative mass spectrometry from SILAC (stable isotope labeling with amino acids in cell culture) labeled cells. Moreover, candidate factors will be downregulated by siRNA to establish their involvement in aggregate disassembly. Such components individually and in combination will then be analyzed for their disaggregation activity in vitro using filter trap assay for the quantification of disaggregation. Cryo-electron tomography of Tau aggregates under various conditions (e.g. during disaggregation) will be carried out in collaboration with Prof. Wolfgang Baumeister (MPIB). Besides contributing to the benefit of humankind, the proposed research work on neurodegenerative diseases will allow me to grow as a researcher and will help me in realizing my true potential as a scientist. The MPIB and the Hartl lab in particular will play an important role in this regard due the availability of state-of-the-art research facilities and an intellectually stimulating environment.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

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

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 171 460,80
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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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.

€ 171 460,80
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