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Deciphering Biomacromolecular Heterogeneity by Single Molecule Mass Spectrometry

Objective

Virus-like particles, nucleic acids, and other biomacromolecular assemblies have shown promise as vaccine platforms, gene therapy vectors, and more. The molecular composition of these contemporary medicines can be incredibly complicated, with a combinatorial explosion of possible variants (e.g. covalent modifications, isoform substitutions, cargo loads, etc.), that together produce an immense degree of chemical heterogeneity. This is further exacerbated by downstream interactions (e.g. receptors, ligands) which must also engage in a multivalent manner.

Such intrinsic heterogeneity hinders both the rational design of macromolecular assemblies and their detailed molecular characterization. There is a critical unmet need for methodologies capable of accurately characterizing the composition of these pharmaceutically important systems. Mass spectrometry (MS) is a promising technique to meet this need but suffers from poor performance under these high-heterogeneity conditions.

DeMIST will develop new high-resolution single molecule MS methods that will exactly address this limitation and revolutionize the compositional characterization of heterogeneous macromolecules and their interactions. DeMIST will combine instrument and method advancements to enable precise trapping and manipulation of individual molecules, that I envision will overcome existing weaknesses and lead to unprecedented increases in the achievable resolution, sensitivity, and information content of these single ion mass measurements.

DeMIST will yield a unique platform for understanding the composition, assembly, structure, and functional elements of complex (bio)macromolecular assemblies, and an avenue to rationally design and potentially improve this important class of therapies. If successful, DeMIST will allow the scientific community to exploit the full benefits of single molecule mass spectrometry to address previously infeasible biomolecular systems.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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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 - HORIZON ERC 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-2026-STG

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Host institution

KOBENHAVNS 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.

€ 2 343 073,00
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
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.

€ 2 343 073,00

Beneficiaries (1)