Project description
Investigating the function of P5 ATPase pumps in our cells
P-type ATP synthases or ATPases are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea and eukaryotes. Prominent examples include sodium–potassium and calcium pumps. Little is known about P5 ATPases, which are found only in eukaryotes and whose malfunctions have been linked to severe neurological diseases. The EU-funded hyP5 project plans to find out more about their substrate specificity and structure as well as their cellular interaction network using different methods, including native mass spectroscopy, cryo-electron microscopy and X-ray crystallography. The project's findings could help unravel the molecular mechanisms of neurodegenerative and cognitive disorders and guide the development of new drugs.
Objective
P5-ATPases are conserved in all eukaryotes and malfunctions in human are associated with severe neurological diseases, such as familial early-onset parkinsonism and autism/language disorders, and with phenotypical traits in yeasts. They belong to the P-type ATPase superfamily, which encompass a range of essential membrane transporters for ions and lipids. Ion pumps such as Na,K-ATPase and Ca2+-ATPase have been studied in great detail during the last decades. However, astonishingly little is known about the P5-ATPases and their actual function, despite their physiological importance in all eukaryotes.
The current proposal focuses on substrate identification and structural characterization of P5-ATPases, as well as investigations of their cellular interaction network. Human P5-ATPases (ATP13A1 through 5, ATP13A2 also known as PARK9) and the yeast orthologues Spf1p and Ypk9p will be subjects of this study. Target proteins will be expressed in their native host (yeast or HEK cells) and subsequently purified and used for activity assays, structural studies, and identification of interaction partners. Native mass spectrometry will identify bound substrates and cofactors, and activity studies will elucidate structure-function relationships. 3D-structures obtained by single-particle cryo-electron microscopy (cryo-EM) and/or X-ray crystallography will reveal catalytic mechanisms and mutational effects. Structural and functional characterization of P5-ATPases can therefore serve as a basis for understanding molecular mechanisms of e.g. neurodegenerative and cognitive disorders and guide novel strategies in disease treatments and drug discovery.
Using my profound experience from my PhD with crystallography of biotechnologically relevant proteins, I wish to pursue a postdoc focused on membrane proteins with a strong potential in molecular medicine and to expand my knowledge of methods in structural biology and molecular cell biology, in particular cryo-EM.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences molecular biology structural biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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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.
8000 Aarhus C
Denmark
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.