Individual Variation In Health During Infection
From Genes To Individuals To Populations
Infection is one of the largest sources of mortality worldwide. This problem remains hard to solve in part because hosts vary substantially in their individual responses to infection, with important, but largely unpredictable consequences for disease spread and evolution. Research in the Vale lab addresses the causes and consequences of individual variation in health during infection.
Broadly, we want to know why there is so much variation in 1) how sick individuals get; 2) how sick individuals make others; and 3) how pathogens evolve in response to this variation.
Most of our work uses the fruit fly Drosophila melanogaster as model of invertebrate immunity during systemic and chronic infections by both viral and bacterial pathogens. Drosophila is the ideal model system to address this challenging problem, as it is arguably one of the best models of genetics, immunity, infection, and behaviour, along with a so far untapped potential as a model for experimental epidemiology. The overall aim of our research is to measure and integrate variation at all these levels, in order to understand how individual changes at the genomic level may impact the health of individuals and populations when faced with infection.
Genetic variation in resistance and tolerance to infection
Resistance mechanisms that reduce pathogen burdens have been widely investigated, but it is becoming increasingly clear that other ways of improving host health, such as controlling damage during infection, also play an important role in host defence. We're currently using the Drosophila Genetic Reference Panel (DGPR) to explore how genetic variation for tolerance to viral infection may affect viral transmission and evolution.
The genetic basis of variation in pathogen shedding
Identifying the causes of variation in transmission among hosts is an important step for successful disease control, but is challenging in the context of epidemics. One approach is to study disease transmission under a variety of genetic and environmental contexts in controlled experimental conditions. We are testing the role of host genetics in different components of viral shedding and spreading in D. melanogaster.
Physiological and behavioural costs of sub-lethal infection
Our knowledge of viral infection and insect health is heavily biased by experimental infections that challenge flies with artificially high viral doses during systemic infections. While systemic infections have been useful in unravelling broad antiviral immune mechanisms, it is unclear whether the morbidity they cause is an accurate reflection of the level of disease, and by extension the fitness costs experienced by flies in the wild. We test the effects of sub-lethal infection with DCV on fly physiological, behavioural and reproductive health.
Infection avoidance behaviours in Drosophila
Behavioural responses are key to limiting the risk of acquiring and spreading infection. The fruit fly Drosophila melanogaster is one of the best-developed model systems for a range of behavioural studies, including individual activity, sleep, aggression, foraging behaviour and courtship behaviour. Our aim is to understand how infection may modify these behaviours in order to gain a more complete understanding of how pathogens impact host fitness.
Risky encounters: contraints between immunity, aggression and courtship
Competition between conspecifics for resources, or courting and mating are important for evolutionary fitness, but are also potentially risky events in terms of acquiring infection from competitors or mates. Physiologically these are connected via the neuro-immuno-endocrine axis. In insects, neurohormones like octopamine and serotonin are activated during stress responses but also modulate the immune response. We are interested in how the conflict between investment in immune responses and aggressive or sexual activities is resolved.
Viral evolution and adaptation in immunocompromised hosts
Understanding pathogen evolution is key to predicting and managing disease emergence. While theory predicts that strong immune responses will generally select for increased pathogen virulence, current work mostly ignores the effect of immune-suppressed hosts on virulence evolution and on pathogen adaptation. We are testing the role of immune-compromised hosts on the evolution of pathogen virulence, and also dissecting the mechanisms that underpin pathogen evolution during adaptation to hosts with variable immune responses.
Do anti-inflammatory drugs increase the risk of disease transmission?
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently recommended for the symptomatic treatment of various ailments. By treating the symptoms of infection without eliminating pathogens, these treatments may facilitate the movement of infectious hosts and possibly increase the rate of pathogen shedding. We are surveying published scientific literature to identify randomized clinical or laboratory trials of NSAID use for a range of infections (influenza, streptococcus, malaria, and trypanosome) to a quantitatively assess the effect of NSAID use on the potential for disease transmission.
The epidemiological and evolutionary consequences of infection tolerance
While we know that resistance mechanisms may affect disease spread and pathogen evolution, the epidemiological and evolutionary consequences of mechanisms that limit and repair damage and allow hosts to tolerate infection are still unclear. We have used a combination of theoretical approaches to understand how conditions or treatments that increase infection tolerance may impact pathogen spread and evolution.