Cell Signaling in Immunity & Disease
Research in the Venom Biochemistry & Molecular Biology lab is focused on understanding signal transduction pathways, which enable cells to respond to stimuli through changes to the cells’ physiological or biochemical state. These signaling pathways play important roles in multiple processes, including the immune response to pathogen infection. Signal transduction pathways are tightly regulated, and deregulated cell signaling contributes to the pathogenesis of many diseases.
We use the Drosophila-parasitoid wasp system in which parasitoids manipulate host signaling via venom virulence factors that are transferred during infection. We find that parasitoid venom proteins target conserved host signal transduction pathways, and so by characterizing the molecular interactions between host and parasite, we hope to better understand pathway regulation and identify novel signaling regulators among parasitoid venoms.
We use the Drosophila-parasitoid wasp system in which parasitoids manipulate host signaling via venom virulence factors that are transferred during infection. We find that parasitoid venom proteins target conserved host signal transduction pathways, and so by characterizing the molecular interactions between host and parasite, we hope to better understand pathway regulation and identify novel signaling regulators among parasitoid venoms.
Experimental SystemWe use the fruit fly Drosophila melanogaster and parasitoid wasps that infect flies as a model host-parasite system. The video at left shows an infection (video credit: Todd Schlenke).
In this system, infection triggers a cellular immune response in the fly. In this response, immune cells surround the wasp egg and become melanized in a process known as melanotic encapsulation. This response kills the invading wasp and allows the fly to continue development. |
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Parasitoids avoid host immunity using venom
However, wasps attempt to block the immune response by injecting venom into the fly during infection. Wasp venoms contain proteins that manipulate host signaling and can inhibit the immune response, allowing the wasp to evade the encapsulation response and successfully parasitize the fly.
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Functional and Comparative Genomics of Host-Parasite Interactions
We use an integrated ‘omics approach to explore interactions between Drosophila hosts and the parasitoid wasps that infect them. We make use of genomic and RNA sequencing, as well as high throughput proteomics and metabolomics to better characterize parasitoid venom repertoires and the alterations they provoke in their Drosophila hosts. We are currently studying the metabolic response to infection, the transcriptional correlates of inflammation, and, in collaboration with the Genomics Education Partnership, we are producing well annotated parasitoid genomes to study the function and evolution of venom-encoding genes.