Objective
This Fellowship proposal will design, fabricate and test novel microfluidic chips for the study of intrinsically disordered proteins (IDPs) by Hydrogen-Deuterium Exchange coupled with Mass Spectrometry (HDX-MS). The research program will use thiol-ene polymerisation to form all components of the microchip allowing fast, reproducible and cheap fabrication. The microchips will incorporate multiple microfluidics channels of varying length and spatially restricted monolith plugs to allow sub-second HDX reactions to occur on-chip. The microchips will circumvent the extensive and error-prone sample pre-treatment steps of current commercial HDX-MS methodology. I will be trained in state-of-the-art HDX-MS technology and will learn how to perform site-specific, light-activated thiol-ene click-chemistry reactions. The microfluidic chips will be used to probe the transient conformational changes of three challenging IDPs of biological and pharmaceutical relevance: a-synuclein, proNerve Growth Factor (proNGF) and Epsin1. α-synuclein is an extensively characterised model IDP, shown by numerous biophysical techniques including HDX-MS to possess some regions of transient structure. α-synuclein will be used during microchip development, providing valuable proof-of-concept and a framework for which to further optimize microchip design if needed. I will then characterise the conformational states and interactions of proNGF; the cleavable pro-element is reported to be disordered, but there is little knowledge of its cellular roles. Previously unreported structural elements of Epsin1, an IDP shown to mediate lipid membrane curvature, will also be probed. HDX-MS will be complemented by electron transfer dissociation (ETD) and ion mobility separation (IM-MS).To be added
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 physical sciences classical mechanics fluid mechanics microfluidics
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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-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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2017
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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.
1165 KOBENHAVN
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.