NSF Award
2419127
The CD300 protein family of immune receptors is encoded by a family of genes present in all mammalian species, including humans. CD300 proteins have been implicated in multiple important roles in human health, including the regulation of cancers, inflammatory diseases, and viral infections. By directly binding pathogens and initiating an immune response, CD300’s play a crucial role in the immune response of humans and other animals. However, the number of CD300 genes varies dramatically between species; for example, rodents, dogs, and armadillos encode more CD300 genes than humans. Little is known about the function of these receptors across different species. Results from this project will shed light on the evolutionary history and functional diversification of the CD300 gene family, providing valuable insights into how these receptors contribute to immune function and disease susceptibility in all mammals including humans. This knowledge has the potential to enhance our understanding of rules that govern the emergence of novel immune function while simultaneously informing the development of new therapeutic strategies. Additionally, the interdisciplinary efforts from this project will yield new K-12 educational modules that align with state standards, will be widely available to public school teachers, and will feature gamified elements to enhance STEM education. This award was co-funded by SBS/DEB.<br/><br/>The human genome encodes seven structurally similar CD300 genes in a single cluster on chromosome 17 which are presumed to have arisen through tandem gene duplication events. Select CD300 proteins have been shown to bind specific phospholipids and are implicated in pathogen recognition and immune defense. However, mammals and other vertebrate species also encode clusters of CD300 homologs with variable gene content across species. Little is known about the functional diversification and evolutionary dynamics of CD300 genes across these lineages. As a consequence, it remains unknown whether the emergence of novel CD300 genes is associated with the development of novel functions. This project will use a multi-omic approach to fill this knowledge gap by mapping the molecular and functional diversification of CD300 orthologs and paralogs, and experimentally testing ancestral CD300 functions. By using a comparative approach to study CD300 genes, the proteins they encode, and the lipids they bind, this research will provide insights into the mechanisms that drive the generation of immunogenetic diversity across vertebrates, while also creating a critical receptor-ligand framework for novel therapeutic development. Additionally, this project will contribute to broader impacts by integrating research findings into STEM education curricula, particularly benefiting underserved middle and high schools, including the Eastern Band of Cherokee Indian community, and fostering scientific literacy and engagement.<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.
