Our research addresses the causes and consequences of individual variation in health during infection.
Most of our work uses the fruit fly Drosophila melanogaster as model of invertebrate immunity during systemic and chronic infections by either viral and bacterial pathogens. Drosophila is the ideal model system to address this challenging problem, as it is a genetically tractable model of immunity, infection, and behaviour, with an untapped potential as a model system for experimental epidemiology.
The overall aim of our research is to understand how individual-level heterogeneity scales up to population-level disease outcomes. Currently our work focuses on three main questions:
1.Why do Individuals vary in how sick they get?
The causes of variation in 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.
2. 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 behavioural, 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.
3. 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.