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Time-resolved imaging of membrane transporter dynamics under physiological ionic gradients

Objective

Without biological membranes, there would be no life as we know it. Lipid bilayers shield cellular content from the environment, creating defined micro environments with specific functionality. Transport of molecules and information across these membranes is carried out by integral membrane protein channels, receptors, pumps and transporters. Living cells maintain chemical gradients and electrical potential differences across their membranes, the potential energy of which can be accessed by the membrane proteins to perform useful work. Indeed, central processes such as metabolic energy generation and nerve impulse propagation directly depend on these membrane gradients. Due to their core role in the life of cells and in the health of living organisms, such proteins represent the majority of all current drug targets. Therefore, membrane proteins have been the focus of intense efforts to obtain high-resolution macromolecular structure information. However, the current lack of experimental methods to carry out time-resolved structural studies of membrane proteins at physiological temperatures and under physiological gradients leaves a gigantic blind spot is our mechanistic understanding.
We will address this challenge by bringing together our complementary expertise in membrane protein biology, time-resolved structural studies, photochemistry and nano fabrication methods. We will link a set of state-of-the-art technologies to build a technology platform, based on a partitioned microfluidic liquid sample environment, optimised for high-resolution, time-resolved, structural studies of membrane proteins by serial electron diffraction from 2D crystals at room temperature and in the presence of physiologically meaningful membrane gradients for the first time. This will allow us to structurally validate models based on biochemical and computational data, and uncover new possibilities for modulation of function by small molecule therapeutics based on allosteric regulation.

Fields of science (EuroSciVoc)

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Keywords

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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.

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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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-2023-SyG

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Host institution

UNIVERSITY OF HAMBURG
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.

€ 7 583 329,00
Address
MITTELWEG 177
20148 Hamburg
Germany

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Region
Hamburg Hamburg Hamburg
Activity type
Higher or Secondary Education Establishments
Links
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.

€ 7 583 329,00

Beneficiaries (2)

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