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REVisiting Antibody structures and repertoires through advances in Mass spectrometry and Proteomics

Objective

In REVAMP, I will create innovative structural mass spectrometry (MS) and proteomics techniques to generate an unprecedented molecular understanding of the diversity and structural and functional characteristics of human antibody repertoires. These repertoires are highly personal and play a key role in our human immune response.
Recently, my research has taken a novel challenging avenue, with a focus on the development of cutting-edge MS-based techniques to better understand antibody structure and function. With these methods, I have started to monitor at the protein level (changes in) endogenous antibody repertoires with clonal resolution, including those induced by antigen-specific polyclonal responses in individuals. Early studies were limited to IgG1, and in REVAMP, I aim to expand the toolbox to the full antibody repertoire, including all (sub)classes of antibodies. I aim to learn how and why antibody profiles in serum, and other body fluids, are alike or distinct, investigating structural, clonal and functional differences over time and between individuals. I will develop technologies to target the sub-repertoires recognizing antigens from pathogens. Following identification by advanced top-down and bottom up de novo sequencing these antibodies will be followed up functionally as potential therapeutic leads.
Special attention will be given to IgM, the largest human antibody, appearing first in the response to an antigen. We recently made the preliminary striking observation that its structure is ill-defined in textbooks, and that human IgM may be quite different from IgM in other mammals. This project will benefit from our recent advances in structural analysis by single molecule mass spectrometry, mass photometry, atomic force microscopy and electron microscopy.
REVAMP will overhaul our current view of the structural diversity of our human antibody repertoire and thereby elevate our understanding of how the human immune system functions.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-ADG

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Host institution

UNIVERSITEIT UTRECHT
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.

€ 2 500 000,00
Address
HEIDELBERGLAAN 8
3584 CS Utrecht
Netherlands

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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.

€ 2 500 000,00

Beneficiaries (1)

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