Glycopolymers as cellular glues

The National Institute of Allergy and Infectious Diseases, a component of the Department of Health and Human Services, awarded $148,614 to Massachusetts Institute of Technology on January 14, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855).

The recipient will develop glycopolymers designed to enhance interactions between immune cells and pathogenic bacteria, creating "cellular glues" that leverage the body's innate immune mechanisms as an alternative to small-molecule antibiotics. The work targets Pseudomonas aeruginosa and aims to assess glycopolymer-mediated bacterial recognition, activation, and signaling by dendritic cells; bacterial killing by macrophages; and improved innate and adaptive immune responses in vivo. The approach is intended to demonstrate how glycan recognition by human lectins influences immune responses to pathogens and could be expanded to address other multidrug-resistant bacteria including Enterococcus faecium and Klebsiella pneumoniae, as well as potential applications against fungal threats or tumor cells.

Performance occurs in Massachusetts. The period of performance runs from January 14, 2026, through January 13, 2029. This is a Project Grant.

Abstract

Antibiotics have improved our ability to treat infections, but antibiotic resistance is now an urgent public health crisis, with global deaths from bacterial infections now exceeding 2 million annually. This rise in resistance demands innovative strategies to combat pathogens effectively. As an alternative to pursuing small-molecule antibiotics, i propose harnessing the body's own immune mechanisms to combat pathogens effectively. I plan to promote interactions between bacteria and human glycan-binding proteins on immune cells for new antimicrobial therapies. This proposal aims to create "cellular glues" - molecules designed to enhance the interactions between immune cells and pathogenic bacteria, ensuring the effective destruction of the pathogens. I will develop glycopolymers that bind to glycan-binding proteins on the surface of the target pathogen, pseudomonas aeruginosa (PSA), and glycan-binding receptors on immune cells, specifically antigen-presenting cells. I will assess the ability of glycopolymers to mediate 1) bacteria recognition, activation, and signaling by dendritic cells, critical informers of t cell response and instructors of adaptive immunity, 2) bacteria killing by macrophages, key phagocytic cells that also process and present antigens, and 3) improved innate and adaptive immune responses in vivo. I envision this approach will provide insight into how glycan recognition by human lectins influences immune responses to pathogens. Moreover, this versatile strategy could be expanded to tackle other multidrug-resistant bacteria like enterococcus faecium and klebsiella pneumoniae, as these pathogens share carbohydrate-binding proteins that are targetable by this design. A successful demonstration of the utility of this approach would lay the groundwork for directing immune responses against growing threats like fungi or even tumor cells.