NSF Award
2316470
The increasing frequency of emerging infectious diseases in humans and animals underscores the need to better understand the immune defenses that organisms deploy to ward off these infections. Notably, the ability of the immune system to fight infection changes as an organism progresses from birth to old age. After all, the risk of encountering pathogens is tied to age-related behaviors and environmental setting, and overly strong immune responses can drain precious energy and fuel autoimmune diseases. As a result, organisms of different ages may derive uneven benefits from the same types of immune responses. Building on the observation that frog (Xenopus laevis) tadpoles contain a less diverse set of adaptive T cells than those of adult frogs and instead rely more on innate-like T cells, the purpose of this project is to investigate the ecological and evolutionary factors that influence changes in T cell immunity as an organism proceeds from younger to older stages of its life. To accomplish this, the project will integrate approaches from the fields of immunology, evolutionary biology and mathematics to investigate T cell receptor diversity across amphibian species currently under existential threat worldwide from a deadly fungal pathogen. The project will provide training to a diverse group of early career scientists and spur the development of active learning modules to educate students about the immune system through the lens of frog biology. <br/><br/>Frogs represent an optimal system to investigate age-structured investment in innate-like and adaptive T cells because of their high diversity in life histories and susceptibility to emergent pathogens. The three project objectives are to: (1) use mathematical models and empirical data to predict when evolutionary history, pathogens, and environment favor T cell diversity within and among life stages on ecological and evolutionary time scales, (2) use RACE-PCR and RNA-seq to quantify T cell receptor diversity for multiple frog species spanning the frog tree of life and known tadpole development times, and (3) experimentally manipulate early-life diet and environment in a laboratory setting to quantify the extent of developmental plasticity on frog T cell receptor diversity and infection outcomes. This proposal integrates classic immunological techniques with evolutionary genetics, mathematical modeling, lab experimentation, and natural population sampling to yield unprecedented insights into the factors that drive the evolution of immune system maturation, plasticity, and diversity. At the same time, this project will train young scientists in interdisciplinary immunology, thus contributing to the formation of the next generation of scientists with interest in immune responses.<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.
