The cervical mucus plug (CMP) constitutes an essential biochemical and physical barrier that
seals the endocervical canal during pregnancy, protecting the gestational compartment from
ascending microbial infection and premature labour. The companion MUCPLUG initiative
(Berzelius-2026-115) is resolving the gestational cervix at single-cell and molecular
resolution, nominating the primary macromolecular constituents responsible for barrier
integrity: polymeric gel-forming mucins, cross-linking transglutaminases, and key accessory
barrier factors. Despite their critical protective function, there is a fundamental absence of
selective, high-affinity molecular probes capable of resolving these proteins, their distinct
structural domains, or their disease-associated assembly states in human gestational mucus.
This deficit impedes translation of emerging cervical biology into clinical assays for barrier
failure and preterm birth risk.
This project employs computational structural biology and generative protein design to develop
targeted mini-protein binders and single-domain antibodies (VHH nanobodies) as diagnostic
capture and detection reagents. Because full-length barrier macromolecules present extended
glycosylated segments alongside structured globular domains, our approach systematically
targets folded structural modules, including mucin von Willebrand factor D and CysD domains,
transglutaminase catalytic surfaces, and accessory-factor interaction interfaces.
Ranked candidates will undergo wet-lab characterization with recombinant expression, surface binding kinetics, and staining of CMP from human and model systems. These reagents will establish the molecular tools required to assesscervical barrier integrity and enable risk stratification for infection-associated preterm
birth.