Evolution and mechanisms of pathogen avoidance

PROJECT SUMMARY
Public health interventions rely on pathogen avoidance behavior because it is often the most immediately
available and effective defense strategy. Avoidance behaviors like social distancing can sharply reduce contact
with pathogens and thus have the potential to control epidemics, especially in response to emerging infectious
diseases, when vaccines and pharmaceuticals are not readily available. Despite the significance of avoidance
behavior, remarkably little is known about its basic mechanisms and evolution. Analogous to the innate and
acquired immune system, hosts can reduce pathogen contact in two ways: 1) innate avoidance: avoidance of
a pathogen without any prior experience of it; and 2) learned avoidance: avoidance that hosts learn after
encountering the pathogen and associating it with damage. These two mechanisms of avoidance appear to
complement one another: innate avoidance should provide strong protection yet may not accurately track
short-term changes pathogen populations. On the other hand, learned avoidance can reactively update based
on the pathogens a host encounters, yet it requires an initial infection to be activated, making it necessarily
less protective. This K99 application will examine the evolutionary and mechanistic interplay between the two
forms of avoidance, identifying their genomic and neural underpinnings.
This K99 application is innovative because it explicitly separates and examines the functional effects of
these two mechanisms of avoidance. The proposed research uses the model nematode host, Caenorhabditis
elegans, and a virulent bacterial pathogen, Serratia marcescens, which the host avoids both innately and through
learning. The research will focus on two main objectives. The first is to identify the role of innate avoidance in
the evolution of pathogen defense. Given its potential effectiveness and primary position, I hypothesize that
innate avoidance represents a major component of the evolved defense against pathogens. Experimental
evolution and whole-genome sequencing will be used to quantify the evolved defense against pathogens that
can be explained by innate avoidance. The second objective is to determine how innate and learned
avoidance are integrated to produce the most effective avoidance responses to the pathogens that are
most damaging. This objective will study innate and learned behavioral and neuronal responses to a diverse
panel of pathogen strains to interrogate how these two mechanisms work together. Together, the training
experiences and expertise developed in genomics and neuroscience will support the applicant’s
transition to research independence. Building on this training, the applicant will develop a research program
that builds on her existing strengths in behavioral biology to examine the functional and mechanistic role of
pathogen avoidance behavior in host-pathogen evolutionary interactions. This project exemplifies the pursuit of
understanding a biological trait across scales, from genes and neurons to individual behavior and health
outcomes, to emergent properties of epidemics and evolutionary processes.

Grant Number: 1K99GM159248-01
NIH Institute/Center: NIH
Principal Investigator: Caroline Amoroso