The overall aim of our research is to understand how individual-level host heterogeneity scales up to population level disease outcomes. Using the fruit fly Drosophila melanogaster as an established model of infection, immunity and behavior, we take an experimental approach to investigate the causes and the consequences of individual variation in immune responses, life-history traits and social behaviors. Currently our work focuses on three broad questions:


Why do individuals vary in how sick they get?

Innate immune regulation of disease tolerance -  In contrast to genetic variation in mechanisms that eliminate pathogens, we currently know little about mechanisms that prevent or repair tissue damage arising from infection, and why they vary among individuals of different genotypes and sexes.  We are leveraging the genetic tools available in Drosophila to investigate the sources of variation in disease tolerance, and to associate disease tolerance phenotypes to specific immune or damage repair mechanisms.

Mitochondrial genetic effects on innate immunity - Mitochondria are increasingly recognized as important mediators of immune responses. However, it is currently unclear how naturally occurring variation in mtDNA contributes to the widespread heterogeneity in infection outcomes. We are using phenotypic, physiological and genomic approaches to test the effect of specific mitochondrial polymorphisms on cellular and humoral responses to infection in Drosophila melanogaster.


Why do individuals vary in how sick they make others?

Host heterogeneity in pathogen transmission is one the major challenges in epidemiology and public health. Achieving a detailed understanding of why hosts vary in their potential to transmit infection is challenging, in part because disease transmission is the outcome of multiple behavioral, physiological and immune processes. A major aim of our work is to identify genetic and environmental drivers of variation fin each of these processes to inform a more useful predictive framework of pathogen spread. Using a combination of experimental and modeling approaches, we're currently working on the following related questions:

- How does infection change social group behaviors that impact disease spread?

- Is host heterogeneity in pathogen transmission a heritable trait?

-  Can we identify genetic loci underlying variation in pathogen avoidance?

- What role does innate immunity play in host heterogeneity in pathogen spread?

- How does individual-level host variation scale up to population level disease outcomes?


How will pathogens evolve in response to variation in host health?

Understanding pathogen evolution is key to predicting and managing disease emergence. Theory predicts that strong immune responses will generally select for increased pathogen virulence, but there are currently few experimental examples of changes in pathogen virulence resulting from selection in hosts with weakened immune responses. We are starting to test the role of immune-compromised hosts on the evolution of pathogen virulence using a combination of experimental evolution and evolve-and-sequence approaches.