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Formation and Characterization of Protein Post-Translational Modifications and Assessment of Cellular Responses by Application of Metals in Biological Systems

Objective

The chemistry of metals is rich and viewed in a biological context its diversity is crucial for a multitude of molecular functions in the living cell. Many of these reactions are very attractive to both academia and industry. In this proposal, I plan to develop novel applications of metal compounds to solve immediate challenges in mass spectrometry-based proteome research, but also will assess the potential risks of using nano-sized metals in our society. First, it is important to develop an efficient enzyme-independent method to synthesize large amounts of biologically relevant C-terminal amidated peptides. Presently, C-terminal peptide amidation poses a challenge in pharmaceutical production due to limitations of the two enzymes used for this purpose. The suggested approach in METALS will examine the specific binding of uranyl to artificially phosphorylated recombinant peptides. Data reveal that subsequent UV irradiation produces C-terminal amidated peptides. I will attempt to minimize the bias inherent in current phosphopeptide analysis, which comes from inefficient inhibition of phosphatases during cell lysis. Application of a recently developed gallium complex during cell lysis should limit the extent of this bias by binding phosphorylated proteins. The neutral conditions involved with the gallium complex reaction should also facilitate the possibility of enrichment of acid labile phospho-histidine peptides of which only a handful have been characterized. Finally, humans are now exposed to increasing amounts of artificially nano-metals applied via consumer products, food packages, and cosmetics. I will investigate this problem using advanced mass spectrometry, confocal microscopy, and biochemical assays of the response of human neural cells to nano-metal particles. The particular focus area will be to elucidate whether the action of nanoparticles in human neural cells may shed new light on understanding of diseases like Parkinson´s disease.

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.

ERC-COG - Consolidator Grant

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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) ERC-2014-CoG

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Host institution

SYDDANSK UNIVERSITET
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.

€ 1 798 750,00
Address
CAMPUSVEJ 55
5230 Odense M
Denmark

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Region
Danmark Syddanmark Fyn
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 798 750,00

Beneficiaries (1)

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