Systematic Investigation of Glucan Functionalized Dendrimers as Tools for Dectin-1 Binding, Activation, and Mechanism of Action
Presentation Type
Poster Presentation
Category
STEM (science, technology, engineering, mathematics)
Abstract/Artist Statement
Our immune system depends on innate cells that carry pattern recognition receptors (PRRs) to recognize and respond against infection. PRRs detect damage-associated molecular patterns from damaged or dying cells, and pathogen-associated molecular patterns (PAMPs) – small molecular patterns of microbes such as β-glucans from fungi. This research delves into the exploration of one PRR, dendritic cell-associated C-type lectin-1 (Dectin-1) and its agonists β-glucans, the PAMPs. Dectin-1 is a key player in anti-fungal defense, and recently discovered as a critical component in immunity against diseases of bacteria, viruses, and certain cancers. β-glucans have been shown to modulate immunity through their polymer length, degree of branching, and their supramolecular structure, however the mechanism of recognition and the agonist properties are poorly understood. To signal Dectin-1 it has been hypothesized that efficient agonist presentation is critical, specifically: (i) β-glucan particle size, (ii) particle superstructure, in particular helical conformations, and (iii) β-glucan chain length and branching. Herein, this proposal seeks to elucidate critical components of activation of Dectin-1 through rational design, formulation, and evaluation of novel polysaccharide dendrimers. To achieve this goal, multiple libraries will be synthesized: polysaccharide functionalized nanoparticles, and trivalent and multivalent dendrimer families bearing a reactive group that selectively reacts with the reducing end of saccharides of glucose, laminarihexose, and lentinan. Dectin-1 activation and mechanism of action will be assessed via appropriate biological assays (e.g. RAW 264.7 cells, human PBMCs, HEK reporter cell lines). Lead β-glucan scaffolds chosen for the best cytokine production in vitro will be further investigated by being formulated onto nanoparticles. When successful, this will help lay the foundation of the specifics of Dectin-1 activation and lead to an advancement in therapeutics.
Mentor Name
Kendal Ryter
Systematic Investigation of Glucan Functionalized Dendrimers as Tools for Dectin-1 Binding, Activation, and Mechanism of Action
UC North Ballroom
Our immune system depends on innate cells that carry pattern recognition receptors (PRRs) to recognize and respond against infection. PRRs detect damage-associated molecular patterns from damaged or dying cells, and pathogen-associated molecular patterns (PAMPs) – small molecular patterns of microbes such as β-glucans from fungi. This research delves into the exploration of one PRR, dendritic cell-associated C-type lectin-1 (Dectin-1) and its agonists β-glucans, the PAMPs. Dectin-1 is a key player in anti-fungal defense, and recently discovered as a critical component in immunity against diseases of bacteria, viruses, and certain cancers. β-glucans have been shown to modulate immunity through their polymer length, degree of branching, and their supramolecular structure, however the mechanism of recognition and the agonist properties are poorly understood. To signal Dectin-1 it has been hypothesized that efficient agonist presentation is critical, specifically: (i) β-glucan particle size, (ii) particle superstructure, in particular helical conformations, and (iii) β-glucan chain length and branching. Herein, this proposal seeks to elucidate critical components of activation of Dectin-1 through rational design, formulation, and evaluation of novel polysaccharide dendrimers. To achieve this goal, multiple libraries will be synthesized: polysaccharide functionalized nanoparticles, and trivalent and multivalent dendrimer families bearing a reactive group that selectively reacts with the reducing end of saccharides of glucose, laminarihexose, and lentinan. Dectin-1 activation and mechanism of action will be assessed via appropriate biological assays (e.g. RAW 264.7 cells, human PBMCs, HEK reporter cell lines). Lead β-glucan scaffolds chosen for the best cytokine production in vitro will be further investigated by being formulated onto nanoparticles. When successful, this will help lay the foundation of the specifics of Dectin-1 activation and lead to an advancement in therapeutics.