Project description
Mapping CMP dynamics to protect infant health
During pregnancy, the cervix undergoes dramatic remodelling, producing a cervical mucus plug (CMP) that helps protect the foetus from bacterial infections. However, little is known about the factors controlling mucus-secreting goblet cells or the properties of the CMP, leaving a gap in understanding preterm birth, which causes hundreds of thousands of infant deaths annually. Existing knowledge from gut and lung mucus studies has not been applied. In this context, the ERC-funded MUCPLUG project aims to use advanced mouse models and biochemical tools to map CMP dynamics, identify regulatory factors, and study bacterial breaches linked to infection. The findings are expected to inform precision interventions to reduce preterm birth and improve infant health.
Objective
During pregnancy, the cervix undergoes dramatic remodelling characterised by the emergence of mucus secreting goblet cells (GCs) that generate a cervical mucus plug (CMP) in the cervical canal. The CMP is thought to act as a barrier that is crucial for maintaining uterine sterility, thereby protecting the foetus from ascending bacterial infections. However, this view is based on relatively little experimental evidence and our knowledge of specific endogenous or exogenous factors that may regulate cervical GC functions and CMP properties is virtually non-existent. This knowledge gap has significant clinical implications, as preterm birth is a common consequence of intrauterine bacterial infections and is associated with up to 0.6 million annual infant deaths.
Over the previous decade, significant research efforts have been made to dissect GC and mucus protective functions in the gut and lungs, while the female reproductive tract has been largely neglected. Fortuitously, much of the knowledge and tools developed by this research can be repurposed to study cervical GCs and the CMP. These include transgenic mice with tagged cervical GCs, null mutant mouse models, targeted mucus biochemical and barrier property analytics, ex vivo mucosal methodologies and large-scale mutagenesis libraries of bacteria that can cause intrauterine infection.
In this proposal we will repurpose these tools to: 1) Define GC and CMP gestational dynamics in pre-clinal mouse models; 2) Identify causal links between endogenous and exogenous factors that regulate GC and CMP functions; 3) Screen for bacterial virulence factors associated with breach of the CMP during pregnancy; 4) Isolate CMP alterations associated with human preterm birth. Addressing these aims will provide new insights into GC and mucus biology, host-pathogen interactions and develop a deeper understanding of female reproductive biology that can applied to the development of precision interventions to reduce infant mortality
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.
- social sciences sociology demography mortality
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences clinical medicine obstetrics
- medical and health sciences clinical medicine oncology cervical cancer
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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.1.1 - European Research Council (ERC)
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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
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(opens in new window) ERC-2024-COG
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405 30 Goeteborg
Sweden
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