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Content archived on 2024-06-18

Circadian clock function by quantitative proteomics and phosphoproteomics

Objective

The circadian clock is an endogenous oscillator that drives daily rhythms in physiology and behavior. The mechanism underlying circadian timekeeping is cell-autonomous and oscillations are generated by interconnecting transcriptional and translational feedback loops. To date large-scale approaches to study molecular circadian rhythms have been limited to the analysis of the transcriptome (mRNA). However, the “true” mediators of cellular functions are proteins. Recent advances in mass spectrometric and bioinformatics technology now allow global quantitation of protein abundance and phosphorylation. The aim of this proposal is to apply the latest methodology in mass spectrometry and bioinformatics, in combination with stable isotope labeling by amino acids in cell culture (SILAC), or in mice, to the investigation of circadian clocks in mammals. I propose to perform a comprehensive quantitative analysis of protein and phosphoprotein circadian oscillations in mouse tissues. The results will be compiled in a database, linked to the European Bioinformatics Institute and available to the scientific community, containing the circadian profiles of all the identified proteins and phosphoproteins in different organs. In addition, I intend to use SILAC-based quantitative proteomics, to identify novel regulators of the circadian transcriptional activity by isolating and analyzing protein complexes bound to clock DNA consensus sequences, and to investigate the molecular interplay between the circadian clock and the DNA-repair machinery. In summary, the objectives of this proposal aim to pioneer the application of SILAC- and mass spectrometry-based proteomics in the quantification of circadian oscillations of proteins and phosphoproteins as well as in the identification of clock components and their interplay with proteins of the genotoxic response.

Fields of science (EuroSciVoc)

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Keywords

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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

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FP7-PEOPLE-IEF-2008
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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-IEF - Intra-European Fellowships (IEF)

Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
EU contribution
€ 222 568,56
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

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