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Illuminating the Dark MicroProteome in Innate Immunity

Project description

Mapping the function of microproteins in immune responses

Short open reading frames in the genome generate microproteins which are typically composed of fewer than 100 amino acids. The emerging role of these molecules challenges traditional views of gene annotation and reveals a hidden diversity of functional proteomes. The ERC-funded MicroIMMUNE project aims to map and study microproteins in innate immune cells. Through a multidisciplinary approach, the research team will identify microproteins under various conditions and investigate their functional roles. The study is expected to unravel the impact of microproteins on immune responses, paving the way towards the identification of novel therapeutic targets such as antimicrobial peptides and immune-modulating drugs.

Objective

Genome annotation, transcriptomic and proteomic pipelines have traditionally dismissed proteins encoded by short open reading frames (sORF) known as microproteins. This provides a pool of unexplored functional genes. Despite the increasing body of work in identifying the microproteome in different model organisms and cell lines, only a few have been functionally studied showing diverse regulatory roles in multiple cellular pathways.

In MicroIMMUNE, I present a 3-aim workflow combining computational and synthetic biology, protein and genetic engineering approaches designed to systematically uncover the microproteome atlas and investigate its interactome and functional role in innate immune cells.

We aim to:
1) Identify microproteins expressed in innate immune cells under resting and stimulating conditions, using state-of-the-art computational and experimental approaches to study the microproteome.
2) Develop genetic code expansion technologies in innate immune cells to incorporate non-canonical amino acids to study the localization and binding partners of microproteins.
3) Elucidate the function of microproteins in innate immune cells by combining genetic engineering with an array of high-throughput functional assays and automated analysis pipelines.

Our research output will address key questions such as: What is the microproteome atlas in innate immune cells and how does it vary upon activation? Where are the microproteins localised and in which protein-protein interactions are they involved? What functions do different microproteins play in innate immune cells?

Understanding the role of microproteins in innate immune cells can revolutionise our understanding of the immune response at a fundamental level and open new avenues for therapeutic interventions in which new antimicrobial peptides or druggable targets could be discovered.

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Topic(s)

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Funding Scheme

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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-2024-STG

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Host institution

UMEA 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.

€ 1 500 000,00
Address
UNIVERSITETOMRADET
901 87 UMEA
Sweden

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Region
Norra Sverige Övre Norrland Västerbottens län
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.

€ 1 500 000,00

Beneficiaries (1)

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