NSF Award
2412256
Immune cells, which protect our body from diseases and disorders, need energy to function. Energy pathways can be manipulated by delivery of metabolites (substances involved in metabolism) which can act to modify immune cell function and metabolism. This CAREER project will utilize new synthesis techniques to generate nanoparticles of metabolites, which will then deliver these metabolites to specialized immune cells called dendritic cells, which are central to the initiation of primary immune responses. The work will advance understanding of energy metabolite-mediated changes in immune cells which can then be leveraged to generate robust immune responses against a variety of diseases including infections, cancer and inflammatory diseases. Additionally, under this project, a computer game will be designed to educate the player on various aspects of metabolism. This project will also engage undergraduate and graduate students and will highlight the importance of biomaterials, metabolism and immune system to the surrounding public community.<br/><br/>Energy metabolism is a key player in all known diseases and disorders, (e.g. cancer and autoimmune diseases); however, there is a poor understanding of energy metabolite-mediated changes in immune cells at the epigenetic level (e.g. transcription factor and histone glycosylation/succinylation). The investigator’s long-term research goal is to study how the metabolite-based biomaterials control the function of immune cells at both epigenetic and functional levels. Towards this goal, the focus of this CAREER project is to understand the energy metabolite, transcription factor and functional protein axis in dendritic cells (DCs). The research presents a method for engineering particles that deliver metabolites to DCs in vitro and in vivo. This project will make engineering contributions by developing synthetic routes of metabolite-based nanoparticles that function as both carrier and cargo. Life science contributions will be made by identifying correlation between metabolites, transcription factors and epigenetic markers in DCs. Importantly, this project will determine the epigenetic changes in DCs due to succinylation/glycosylation of transcription factors and histone. The joint approach of immunology and engineering will help further develop the field of energy metabolite-based control of DC function, which has exciting potential for the discovery of new drug targets and development of therapeutics that treat an array of immune system-associated diseases.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
