B.A. (1996), Ithaca College
Ph.D. (2000), Colorado State University
I am currently recruiting graduate and undergraduate students interested in joining the rapidly expanding field of vector biology and vector-borne disease. Students with backgrounds and interests in entomology, genetics, molecular biology, or virology are encouraged to contact me via email.
Research in my laboratory is concerned with understanding the molecular and genetic interactions between arboviruses and their mosquito hosts. Research projects are based in the molecular virology of arboviruses (dengue viruses, Sindbis) as well as the molecular biology and genetic manipulation of the vector mosquito, Aedes aegypti.
Generation of pathogen-resistant mosquitoes
Previous work has demonstrated the feasibility of generating genetically-modified pathogen-resistant mosquitoes using RNA interference. Two of the large open questions remaining include: How can such genes be driven to fixation in a natural mosquito population in a relatively short amount of time?, and what is the potential for the targeted pathogen to escape from interference?
Gene drive refers to the inheritance of a gene at super-Mendelian rates, which should cause a given allele to increase in frequency within a population every generation, with the eventual result being fixation of said gene in the target population. Work in my lab centers around two potential gene drive mechanisms: homing endonucleases and transposable elements.
Homing endonucleases are selfish DNA elements encoding a site-specific endonuclease. The recognition sequence for a given homing endonuclease can range from 14-40bp, meaning they can be expected to generate very few double-stranded DNA breaks in a particular genome. Following DNA cleavage, host-mediated repair using gene conversion results in a duplication of the homing endonuclease gene. Research projects in my lab aim to determine the ability of homing endonucleases to function in Ae. aegypti; and evaluate whether the repair of germline-specific homing endonuclease-generated dsDNA breaks can result in heritable gene conversion.
Transposable elements are also a potential gene drive mechanism. Class II transposable elements also encode a single gene, the transposase, which as opposed to recognizing a single sequence, recognizes inverted repeat sequences flanking the ORF. The transposae mediates both an excision and re-insertion to a new chromosomal location. Like homing endonucleases, repair of the double-stranded break results in gene duplication. Work in my lab investigates the design an autonomous transposable element (controlled by nanos or other germline-specific regulatory elements) as a possible method of driving virus/parasite-resistance genes into naïve mosquito populations.
RNA interference is a critical innate immune pathway in disease vector mosquitoes, and plays an indispenble role in the control of arbovirus infection. While some of the main effector genes are known, how these genes are regulated and what other critical components might be necessary are not known. In collaboration with the laboratory of Dr. Kevin Myles, we have developed a transgenic "sensor" strain of Ae. aegypti which dispays conditional green fluorescence in the eyes under conditions where RNAi has been compromised. Using this "sensor" strain, we are in the process of identifying and characterizing new components on the RNAi pathway in mosquitoes.
In a similar fashion, we know very little about how mosquitoes defend themselves against foreign DNA elements. What are the effects of transgene insertions on chromosome structure? Will the mosquito recognize and shut down a transgene over time? And what effect will this have on the potential for genetic control? The answers to these questions are of vital importance to the implementation of a successful genetic control strategy.
A key component of my work is to raise public awareness of the potential benefits and limitations of genetically-modified organisms related to the control of disease: within the local community; among elected representatives; and, most importantly, in areas where these strategies could be implemented.