NAISS
SUPR
NAISS Projects
SUPR
De novo design of diagnostic protein binders and nanobodies against cervical mucus-plug barrier proteins
Dnr:

NAISS 2026/4-1499

Type:

NAISS Small

Principal Investigator:

Moe Xylander

Affiliation:

Göteborgs universitet

Start Date:

2026-08-28

End Date:

2027-09-01

Primary Classification:

10203: Bioinformatics (Computational Biology) (Applications at 10610)

Allocation

Abstract

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.