Jessica Hua and Vatsan Raman receive NSF CAREER awards

Jessica Hua, associate professor in the Department of Forest and Wildlife Ecology, and Vatsan Raman, associate professor in the Department of Biochemistry, were selected to receive National Science Foundation CAREER awards this year. The Faculty Early Career Development (CAREER) Program offers NSF’s most prestigious awards in support of early-career faculty who have the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization. Details about their funded projects are below.

Jessica Hua
Evolutionary Disease Ecology – Can evolutionary responses to environmental change modify the biodiversity-disease relationship?

Understanding patterns of emerging infectious diseases is at the forefront of global interest. This research asks: Why are some communities more vulnerable to diseases than others? To address this broad question, this work focuses on understanding how biodiversity influences community disease risk. While many studies find that communities with higher biodiversity have lower disease risk, some studies show no effect of biodiversity on disease risk and others even find the opposite effect (i.e. communities with higher biodiversity have higher disease risk). Overall, the idea that biodiversity can reduce disease risk is attractive because it suggests that protecting biodiversity has clear benefits to both nature and society. This research tests the central hypothesis that cryptic differences in populations’ responses to past conditions (i.e. evolutionary history) plays an important role in understanding when biodiversity will reduce disease risk. This CAREER award will develop a summer research and outreach program that supports undergraduate artists, engineers, biologists, and educators and a 3rd-grade citizen science training program.

The Biodiversity-Disease (BDD) Relationship has generated considerable attention as a theoretical framework for predicting community disease outcomes. Yet, limited consensus on the generality of the BDD relationship has been reached leading to repeated calls to uncover factors shaping the magnitude and direction of the BDD relationship. This research tests the hypothesis that intraspecific host variation, generated by divergent evolutionary histories, plays a cryptic role in shaping the direction and magnitude of the BDD relationship. To this end, the research focuses on amphibian host-parasite interactions and takes advantage of an experimentally tractable group of focal wood frog populations that exhibit intraspecific variation in parasite susceptibility as a result of evolving in contrasting environments. The researchers will first evaluate the contribution of intraspecific variation to shaping the BDD relationship by generating mesocosm communities that vary in amphibian host species diversity and focal host intraspecific diversity. Second, to integrate ecological context into our understanding of how intraspecific variation influences the BDD relationship, the researchers will conduct lab and mesocosm studies testing whether intraspecific variation in focal hosts can shape the BDD relationship by modifying (a) competitive, (b) predator-prey, or (c) host microbiota interactions. Third, to complement the controlled experimental studies, the researchers will conduct citizen-led field surveys to evaluate whether intraspecific variation modifies the BDD relationship in more complex natural ecosystems. Towards this aim, the researchers will develop a two-step integrated education-research program: (1) Content development: Researchers will design an interdisciplinary program where undergraduates work with local communication and education experts to develop a citizen training program. (2) Implementation: Citizens will complete training program and collect field data that contributes to the overarching research goals. Collectively, this integration will facilitate citizen data collection efforts, diversify STEM training and engagement, and broaden access to authentic research opportunities.

Vatsan Raman
Mapping the functional landscape of bacteriophage-host interactions at molecular resolution

While many bacteria are inoffensive or even beneficial to humans, some are harmful pathogens. Finding a way to kill the pathogenic bacteria without harming the beneficial microbes could prove a useful tool. Phage research has emerged as an exciting new frontier in microbiology due to its role in shaping microbiomes and as a potential therapy against drug-resistant bacterial infections. Phages identify and interact with their specific bacterial target through a structure known as the receptor-binding protein. While characterization of thousands of natural phages have occurred, limited studies have explored the molecular mechanisms that govern phage-host interactions through the receptor-binding protein. This research will apply genome engineering, high-throughput DNA sequencing, and viral metagenomics approaches to elucidate how protein sequences encode function. The research will be the basis for numerous viral-focused educational outreach activities, including for middle school classrooms, to expose a diverse audience to relevant, real-word issues in viral and bacterial biology.

Receptor binding proteins mediate the interaction of a phage with its bacterial receptor(s) and thus constitute key determinants of a phage’s host range and activity (virulence). Phages exhibit high functional plasticity through genetic alterations of these proteins to adapt to new host environments. Despite extensive research to address the mechanisms associated with this interaction, it remains unclear how receptor binding protein mutations influence phage activity and host range. This work will examine the molecular rules of receptor binding proteins of coliphages, viruses that infect coliform bacteria, and will seek to exploit those rules to engineer synthetic coliphages with specificity for foodborne pathogens. In addition, the project will study receptor binding proteins from another group of phages that have a more complex receptor binding architecture that permits the phage to both enzymatically degrade the capsule that protects certain bacteria and also to bind to host receptors. To understand this process mechanistically, mutational and metagenomic scanning will be used to map and identify the function of every sequence in the receptor binding protein of a phage with the dual capability. These mutational studies will inform protein design strategies guided by machine learning to engineer new phage-host interactions. The project has the potential to create tools that could be broadly adopted by the research community to study sequence-function relationships in a variety of phage-host systems.