You're involved in some pretty complex research. When you talk to non-scientists, how do you explain what you do?
My lab takes a comparative approach to investigate common immune responses of plants and invertebrates to RNA virus infection. These studies are important for the control of plant viruses and mosquito-borne human viruses, and may also help understanding human antiviral immunity in general.
As your work has helped show, RNA interference (RNAi, also called RNA silencing) is employed by living things from all over the tree of life as a means of fighting viral infection. Are there any organisms that we know don't employ RNAi? Are there any you suspect do not employ RNAi? Why?
Fungi, plants, and invertebrates all produce virus-derived small interfering RNAs (siRNAs) to direct antiviral immunity by RNAi. A distinct set of proteins in bacteria also mediates a form of nucleic acid-based antiviral immunity analogous to RNAi. Currently, RNAi is not considered to play a natural antiviral role in vertebrates. However, this view may prove incorrect sooner or later because the RNAi pathway is highly conserved and the life cycle of viruses is essentially identical in invertebrates and vertebrates.
A recent paper of yours described the production of virus-derived PIWI-interacting RNAs (piRNAs) in Drosophila. What are these piRNAs and why is it significant that they're produced by the host?
piRNAs are several nucleotides longer and products of a different, animal-specific biogenesis pathway as compared to siRNAs and microRNAs. Detection of RNA viruses by the piRNA pathway in Drosophila (and in mosquitoes shown subsequently by others) suggests a novel antiviral function for piRNAs in addition to their known role in genome defense against transposons and repetitive elements.
In another aspect of that paper, you and your colleagues developed a culture-independent approach to discovering novel viruses. Describe your method.
The method is based on our 2008 discovery of the overlapping nature of virus-derived siRNAs produced by the host immune machinery. It includes (i) deep sequencing of total host small RNAs, (ii) computational assembly of overlapping small RNAs, and (iii) identification of viruses in the host by virus database homology searches using the viral genome segments assembled from the overlapping viral siRNAs. We have recently published a new algorithm that interrogates total host small RNAs libraries for homology-independent discovery of viroids, a unique class of naked RNA pathogens known to cause disease only in plants.
Where do you see your field in 10 years?
It took less than two years to demonstrate the innate immunity function of Toll-like receptor pathway in mammals following the pioneering Drosophila study. I expect to see some solid evidence for an antiviral role for RNAi in mammals, reported in Drosophila more than 10 years ago, and a detailed genetic dissection of the antiviral immunity pathway using model systems established in Drosophila, C. elegans and Arabidopsis.
If you had to change careers today and you could do anything, what would you do?
I can’t imagine a better job than what I do now.
What’s your favorite science book?
ASM Press textbook “Principles of Virology” by S.J. Flint, L.W. Enquist, V.R. Racaniello and A.M. Skalka.
What is something about you that most people don’t know?
I had two years of farming experience before entering college.