Project description
Host interactions with Streptococcus pneumoniae
Streptococcus pneumoniae is normally harmless but can become pathogenic in vulnerable populations and cause pneumoniae, meningitis and septicaemia. Understanding how the host maintains harmless colonisation or triggers a response against invasive disease is central for managing S. pneumoniae infections. With the support of the Marie Skłodowska-Curie Actions programme, the KDM6B-BACHROM project will investigate host chromatin responses to S. pneumoniae, focusing on histone modifications mediated by the demethylase KDM6B. Using a nasal epithelium model, the research will identify KDM6B binding partners, define tissue responses to colonising and invasive strains, and characterise the molecular pathways regulating immune homeostasis. Ultimately, the project will uncover mechanisms of host-bacteria crosstalk with potential therapeutic relevance.
Objective
Streptococcus pneumoniae is a pathobiont that is a top 10 WHO priority pathogen. Whilst it is commonly carried in the nasal cavity of healthy populations, it also causes invasive disease in vulnerable populations causing pneumoniae, meningitis, and septicaemia. However, the host factors involved in maintaining colonisation or triggering an immune response are currently unknown, and my research project aims to address this knowledge gap. In line with the expertise of the Hamon lab, the project will focus on bacteria-induced histone modifications which corelate with altered host gene expression. Following on the discovery that a colonising and asymptomatic strain of S. pneumoniae activates the histone demethylase KDM6B for immune homeostasis, the project will characterise the KDM6B-mediated response at the molecular level in a physiological model of nasal epithelium. Specifically, the research objectives are to:
1) Identify KDM6B binding partners during S. pneumoniae challenge
2) Define the nasal tissue response to S. pneumoniae
3) Characterize the KDM6B-mediated nasal tissue response to the bacteria
The host laboratory has a powerful model of reconstituted nasal epithelium model in which responses to a colonising or an invasive strain of S. pneumoniae can be evaluated. I will use and gain expertise in cutting edge techniques such as mass spectrometry to determine KDM6B binding partners and single-cell RNA sequencing along with spatial transcriptomic technology (MERFISH) to analyse host cell responses at the single cell level.
The field of bacteria mediated histone modifications is in its infancy and offers a large margin of discovery. Altogether this project will advance our understanding of the signals and pathways that regulate the balance between homeostasis and infection and will identify and characterise original mechanisms of host chromatin-bacteria cross talk which could be targeted for therapeutic purposes.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine pneumology
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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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.
75724 Paris
France
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