NSF/BIO-UKRI/BBSRC: The role of gene copy number variation in host-microbe interactions

About This Grant

Organisms rely on a diverse repertoire of immune pathways to detect and respond to microbes, thereby enabling mutualistic interactions and preventing infection. Variation in the number of genes composing the immune system varies widely across the tree of life and has been hypothesized to be important for interactions with the microbiome, including differential susceptibility to pathogens between individuals. Yet, its role in regulation and innovation for marine invertebrates remains poorly understood. The research team will utilize a coastal sea anemone to study the impact of copy number variation of key immune genes in the ecological and evolutionary dynamics of this symbiosis. Insights from this research will provide actionable information for translation into efforts to conserve species critical for aquaculture and ecosystem resilience. This project will provide mentoring and training for trainees across educational stages at the University of North Carolina at Charlotte to prepare them for careers in STEM, including biotechnology. Additional research and educational opportunities will be provided through course-based undergraduate research experience, outreach through a local science museum, and a new University of North Carolina at Charlotte center focused on the intersection of biology, computation, and environmental health. Knowledge of the environmental, genetic, and molecular factors involved in modulating expression of the innate immune system is essential to understand and predict how host species shape their microbiomes and respond to pathogens. The integrative research approach in this project will determine how variation in copy number of key immune genes among individuals of a cnidarian species relate with changes in the survival, physiology, associated microbial community, and molecular responses for this animal host. Nematostella vectensis has been utilized as a model for ecological and evolutionary genomics by the research team to understand the genetic variability of this invertebrate, the role for nucleotide variation in local adaptation, and heterogeneity of the microbiome. The proposed research will utilize (a) comparative genomics and transcriptomics to determine the extent and impact of copy number variation in populations of this species, (b) metagenomics and experimental infections to determine the dynamics of the microbial community, and (c) the diverse molecular and genomic toolkits including transgenesis for N. vectensis to test long-standing hypotheses concerning the impacts of gene duplications on host-microbe interactions. The team will integrate these data to connect genotype to phenotype to illustrate the phenotypic consequences of immune gene copy number variation and the evolutionary/regulatory mechanisms facilitating innovation and specialization of the innate immune system. 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.