Research
My research seeks to answer three fundamental questions:
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(1) How does the environment impact disease outbreaks?
(2) When, why, and how often do pathogens spill over into non-reservoir hosts?
(3) How do pathogens emerge in non-reservoir host species and change during emergence?
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I aim to understand how environmental drivers, impact disease outcomes within and across host species. My lab focuses on understanding processes that act at the population and within-host levels. We use a model system - Caenorhabditis nematodes and their native viruses - in our research.
Caenorhabditis "worms" and Orsay virus study System
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To “emerge”, a pathogen first must jump from one host species to another (“spillover”) and then adapt to transmit in the new host population. Despite the extraordinary threat to human health, we know little about drivers of spillover and emergence. Natural emergence events are rare and usually not observed in process. Few laboratory systems permit replication of large host populations (necessary to capture rare events) with natural transmission (required for evolutionary studies). The lack of systems to test hypotheses has been an obstacle to understanding disease spillover and emergence. In collaboration with Dr. David Kennedy, I developed a system - Caenorhabditis worms and Orsay virus - that fills this vacuum.
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Caenorhabditis comprises dozens of worm species including the model C. elegans. These animals have fast life cycles and grow to large populations on 6 cm plates (right). Ecological conditions are easily manipulated with standard laboratory tools. Orsay virus, a natural pathogen of C. elegans, is a mildly virulent RNA virus that infects gut cells and transmits via the fecal-oral route. Of 44 Caenorhabditis species, I found 13 susceptible (spillover) species and observed emergence in three (Shaw & Kennedy 2022). These findings yield a powerful new system in which we can manipulate variables and examine how they influence spillover and emergence.
Plates of Caenorhabditis worms on lab benchtop.
Magnified Caenorhabditis worms.
How does the environment impact disease outbreaks?
The environment is an important modulator of disease, affecting epidemic size and the evolutionary potential of pathogens. Environmental impacts on disease in reservoir populations might be particularly important for spillover and emergence: larger epidemics might increase exposure for spillover hosts and genetic changes in pathogens might impact their ability to infect and transmit in spillover hosts.
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Abiotic and biotic conditions modulate pathogen transmission directly or indirectly (acting through hosts).
We will investigate how consequences of anthropogenic change (e.g. reduced resource quality or increased temperature) affect epidemic size and evolution of Orsay virus in reservoir (C. elegans) populations. These stressors could impact pathogen dynamics though host population size, behavior, physiology, and immune function. Both stressors are straightforward to manipulate in worm populations, and responses (e.g. feeding rates, reproductive rates) and infection outcomes (prevalence and intensity) are readily measurable. We will study evolutionary implications of these stressors by maintaining virus in stressed and non-stressed populations, comparing phenotypes of evolved and ancestral viruses in common garden experiments, and analyzing viral genomes.
When, why, and host often do pathogens spill over into non-reservoir hosts?
A pathogen can spill over when it encounters a new host and it can infect, evade the host's immune response, and exploit its resources. Keeping exposure doses constant, I found that closely related worm host species have similar susceptibilities to Orsay virus, likely due to similar within-host conditions (see figure to the right from Shaw & Kennedy 2022). What are the shared traits of related species that make them susceptible? We will investigate determinants of spillover in this system by examining traits (e.g. feeding rates, gut pH, population growth rates, candidate genes) and variation in susceptibility within and across species. Determining which host traits predict susceptibility will add to the value of this system for studying spillover and emergence.
Susceptibility to Orsay virus is associated with phylogenetic relatedness among Caenorhabditis species. Points above the dashed line indicate infected populations. The right panel contains species with unknown phylogenetic placements; color indicates clade hypotheses. See Shaw & Kennedy 2022 for more information.
How do pathogens emerge in non-reservoir host species and change during emergence?
Most spillovers sputter out without causing extensive outbreaks. It is rare for pathogens to emerge in new hosts because pathogen fitness suffers in the inhospitable environments of hosts to which they are not adapted. I'm interested in identifying the ecological conditions and evolutionary mechanisms that facilitate this process through experimental evolution studies in reservoir and novel host populations. By sampling virus throughout emergence, we can document phenotypic (e.g. infectivity, virulence, transmission potential) and genetic changes in viruses in the process of emergence. We will identify viral traits that are important for emergence in novel hosts (e.g. capsid structure) and how ecological conditions impact the evolution of emerging viruses.