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Unraveling the dark matter of infectious diseases, environmental and genetic factors tipping the balance towards NCDs

Project description

Advanced research connects the dots between infections and immune diseases

Understanding how infections contribute to immune-related diseases, such as lupus or multiple sclerosis, is challenging. These diseases are influenced by a complex mix of factors, including infections, genetics and the environment, making it difficult to pinpoint specific triggers. The EU-funded ID-DarkMatter-NCD project plans to use advanced technology to study thousands of microbial elements. Researchers will screen antibody responses to 600 000 ID antigens and profile 6 000 patients across six immune-related noncommunicable diseases using multi-omics and personalised genotyping. Using machine learning for data analysis, the team will help uncover how infections interact with the immune system to spark disease. Project findings could aid in understanding, preventing and treating these conditions, offering hope to millions affected by immune-related diseases worldwide.

Objective

While it is known that post-COVID-19-condition (PCC) is caused by SARS-CoV-2 infection, for most other immune-related noncommunicable diseases (IR-NCDs), no such infectious disease (ID) triggers have been identified (yet). Many IDs exist that could potentially cause IR-NCDs, however these microbes have large genomes encoding many antigens possibly associated with IR-NCDs. Given that it is challenging to measure all these 100,000s of structures in parallel, they represent the dark matter of ID-immune interactions.
Furthermore, exposure to an ID alone typically does not trigger development of an IR-NCD: For example only a subset of patients infected with SARS-CoV-2 develop PCC. So, genetic- and environmental aspects also affect the onset of IR-NCDs, but the exact factors are unknown for most IR-NCDs.
Here, we aim to 1.) identify IDs triggering IR-NCDs by screening for antibody responses against 600,000 ID antigens, and 2.) to disentangle environmental and genetic factors affecting the transition from IDs to IR-NCDs. We will combine novel multi-omics approaches and technologies for personalized genotyping of HLA and adaptive immune receptor genes to deeply profile 6,000 patients of six IR-NCDs (PCC, multiple sclerosis, ME/CFS, rheumatoid arthritis, lupus, IBD) to identify novel biomarkers and disease mechanisms.
This project will represent the largest and most deeply profiled systematic study of multiple IR-NCDs with layered datasets allowing for comparative analyses yielding insights into shared mechanisms and potential differences in the role of IDs between IR-NCDs. Building on associations identified from population scale and clinical cohorts, we will demonstrate causality in gnotobiotic mouse models, and leverage machine learning (ML) algorithms to predict disease progression and response to treatment. The combination of novel assays with ML represents a broadly applicable pipeline that can be used for studying the interplay of any other IDs/ IR-NCDs.

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Topic(s)

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HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-HLTH-2023-DISEASE-03

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Coordinator

MEDIZINISCHE UNIVERSITAET WIEN
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.

€ 2 562 000,00
Address
SPITALGASSE 23
1090 Wien
Austria

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Region
Ostösterreich Wien Wien
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.

€ 2 562 500,00

Participants (10)

Partners (1)

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