CAREER: Glycoprotein mimetics with tailored galectin-binding properties based on self-assembled glycopeptide nanofibers

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Technical abstractThis award by the Biomaterials program in the Division of Materials Research proposes to synthesize and study nanofibers that mimic the structure, composition, and function of natural glycoproteins to modulate the biological activity of galectins, a family of carbohydrate-binding proteins that act as signaling molecules in various normal and pathological processes. The proposed nanofibers are fabricated via self- assembly of peptides. Nanofiber carbohydrate content can be varied by mixing peptides with and without a pendant carbohydrate at different ratios in the pre-assembled state. Carbohydrate chemistry can be precisely altered post-assembly via enzymes derived from natural carbohydrate synthesis pathways. Nanofibers with tailored carbohydrate content will be used as tools to study galectin-glycoprotein interactions, which in turn will inform design of new therapeutic biomaterials that can modulate galectin bioactivity for various applications, including immunotherapy, cancer, and viral prophylaxis. These research efforts will be coupled with outreach efforts that provide middle school, high school, and undergraduate students with hands-on engineering experiences to stimulate interest in research and prepare them for STEM careers, with a particular emphasis placed on attracting students from under- represented communities throughout northern Florida. Through these experiences, students will develop important scientific and leadership skills to prepare them for independent STEM careers.Non-technical abstractThis proposal describes research to create biomaterials that can modulate the activity of galectins, and could be useful in treating various conditions, including autoimmunity, cancer, and viral infection. Galectin activity is modulated in natural tissues via interactions with carbohydrates attached to proteins, or "glycoproteins". Efforts to create therapeutics that can interfere with galectin-glycoprotein interactions are often challenged by difficulties associated with carbohydrate synthesis and the lack of clearly defined correlations between carbohydrate chemistry and galectin binding specificity. This research will address these limitations by developing a new method to fabricate nanofibers with precise carbohydrate composition, and then using these nanofibers to study and define galectin-glycoprotein binding parameters. In turn, these parameters will inform the design of biomaterials that can enhance or inhibit activity of a particular galectin according to the intended therapeutic application. Outreach efforts are proposed to foster early interest in STEM careers that is sustained through collegiate education. In particular, these outreach efforts will develop hands-on engineering curricula to introduce middle school students to fundamental engineering concepts, enable one high school student per year to participate in a 7-week full-immersion research experience in the laboratory of the Principal Investigator, and provide undergraduate and graduate students with research and mentoring opportunities.