To achieve our goal, MUC4health has two specific aims:

1) To engineer, using precise chemoenzymatic synthesis, homogeneous well-defined mucin glycodomains: By controlling the action of specific GTs we will break the limits on chemoenzymatic synthesis by generating tumor-associated mucin glycodomains with an unprecedent chemical diversity (size, peptide sequence, glycan density and diversity). 

2) To control the balance between the blocking versus signal induction capacity of mucin glycodomains. The molecular and cellular mechanisms of tumor-associated mucin glycocode recognition by key immune lectins will be deciphered, providing an unprecedented structure-immune relationship data.

On this basis, MUC4Health aims at modulating lectin-mediated immune responses by chemically adjusting the size, peptide sequence and the chemical diversity & density of the glycans on the mucin glycodomains. Hence, MUC4Health will generate:

1) Small mucin glycodomains, which are expected to penetrate better in the tumor microenvironment than antibodies, acting as antagonists, blocking lectin-mediated suppression. This is beneficial to combat cancer since tolerance is alleviated and anti-tumor immunity is promoted.

2) Large mucin glycodomains, with multiple tandem repeated domains to mimic the tumor-associated presentation, to act as agonists, inducing signaling and providing tolerance. This effect counteracts unwanted or exacerbated immune reactions and restores tolerance in case of autoimmunity.

To complete its ground-breaking objectives the team of MUC4Health will synergistically combine precise chemoenzymatic methods and molecular biology, with glycomics (glycan microarrays and MS) and biophysical and structural techniques, NMR assisted by molecular modelling, with immunological assays. From this bottom to top approach, from chemistry to immunology, MUC4Health will potentially yield novel therapeutic immunomodulatory strategies.