I am broadly interested in the interaction of infection with classically non-immune physiology and pathways. The immune system is composed of processes that protect organisms against disease, but only a subset of these are covered in most immunology classes. This bias is often due to a focus on factors impacting resistance – the ability to control pathogen load. However, there are also factors that may impact tolerance – the ability to withstand the damage and consequences at a given pathogen load. Changes in metabolism, behavior, and perception can all influence survival during infection. Using Drosophila melanogaster as a model host, I am dissecting the interactions between host immunity, metabolism and behavior.
This model system is very amenable to student research and I have developed many projects accessible to undergraduate and even high school researchers. Drosophila are very easy to maintain and have many genetic tools easily available for order from stock centers. We also have a suite of natural pathogens that enable study of naturally evolved bacterial-host interactions. In addition, the Drosophila community is very collaborative and this enables me to access training from experts in Drosophila metabolism and behavior. To learn more about using fruit flies as an infection model - watch our short JOVE video, which was authored by two of my student mentees!
I welcome emails from any interested students or potential collaborators (email@example.com)!
Effects of chronic infection on host physiology and behavior
Infections sustained for a lifetime are one of the most widespread categories of infections, yet these chronic infections are often neglected by researchers in favor of an emphasis on high mortality, transient acute infections. Humans can be chronically infected with a diverse array of parasites while exhibiting minimal clinical symptoms (e.g. Toxoplasma gondii, varicella zoster virus, Borrelia burgdorferi). Chronic infections are sometimes associated with nutritive and behavioral disorders suggesting that these diseases have the potential to metabolically and behaviorally alter their host. Using Drosophila melanogaster as an experimental host and Providencia rettgeri as a model pathogen, I have found that chronic infection causes flies to be better at fighting future infections and more susceptible to starvation stress. Our current work focuses of dissecting the mechanisms behind this apparent trade-off.
Interaction between immunity and metabolism
Immunity and metabolism are intimately linked; manipulating metabolism, either through diet or genetics, has the power to alter survival during infection. The relationship between metabolism and immunity is complex and the results depend upon the pathogen tested and measured immune output. During my graduate work in the Schneider lab, I found that infection of flies with Listeria monocytogenes causes a whole suite of changes in host metabolism (pdf). I am now working to dissect the effect of the natural pathogen, Providencia rettgeri, on the host metabolism while also taking into account the bacteria's metabolic needs.
Sensory detection of illness
Social interaction of infected individuals impacts disease transmission and mate choice in a diversity of animals, although the mechanisms contributing to these behaviors are largely unknown. Our preliminary data suggests that flies carrying chronic infection keep a further inter-individual distance from their nearest neighbor than healthy flies do. Is this increased distance due to sensory detection of illness? Or is it due to direct contact with bacterial products?
If you look closely you'll see Austin, a high school student who worked on social spacing with me in Summer 2013 as part of a Research Apprenticeship in Biological Sciences.
Variation in genetically identical individuals
Homogenous lab stocks that are experimentally infected with the same dose have large variation in bacterial load after about 12 hours, yet most often we look at aggregate measurements of the population. While much can be gleaned from aggregate measures, I am interested in studying what is different between these individual flies. Is there something predictable about the individual flies with the highest and lowest loads?
The image to the right shows the variation in immune induction in individual flies 24 hours after infection and Eliana, a junior at Cornell, tested whether this induction correlates with bacteria load and host survival.