Students
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 e-mail.
Research Interests
Research in my laboratory is concerned with developing genetic control
strategies to supplement the currently available methods of containing and
eradicating vector-borne diseases such as source reduction, vaccination,
insecticides and anti-pathogen drug development. 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
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.
Mosquito-transgene/ Mosquito-pathogen interactions
Current work aims to understand the potential for pathogens such as dengue
viruses to escape from RNAi. This requires a full understanding of the
components and regulation of the RNAi pathway in mosquitoes. With the complete
genome sequence of the mosquitoes Anopheles gambiae and Aedes aegypti
now available, a comprehensive strategy for identifying genes involved in the
RNAi pathway is underway.
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.
Public Outreach
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.
The ultimate goal of this research is to introduce one or more anti-pathogen
effector genes into a natural, pathogen-transmitting mosquito population via a
transposable element- or homing endonuclease-derived gene drive system in an
ethical, legal and fully disclosed fashion, with the result being complete
pathogen resistance among the target mosquitoes, and abrogation of disease
transmission.
Publications
Adelman, Z.N., Jasinskiene, N., Onal, S., Juhn, J., Ashikyan, A.,
Salampessy, M., Macauley, T., James, A.A., (2007) nanos gene control
DNA mediates developmentally-regulated transposition in the yellow fever
mosquito, Aedes aegypti. Proc Natl Acad Sci U S A 104(24),
9970-9975.
Franz, A. W., Sanchez-Vargas, I., Adelman, Z. N., Blair, C. D., Beaty,
B. J., James, A. A., and Olson, K. E. (2006). Engineering RNA
interference-based resistance to dengue virus type 2 in genetically modified Aedes
aegypti. Proc Natl Acad Sci U S A 103(11), 4198-203.
Calvo, E., Walter, M., Adelman, Z. N., Jimenez, A., Onal, S.,
Marinotti, O., and James, A. A. (2005). Nanos (nos) genes of the
vector mosquitoes, Anopheles gambiae, Anopheles stephensi and Aedes
aegypti. Insect Biochem Mol Biol 35(7), 789-98.
Adelman, Z.N., Jasinskiene, N., Vally, K.J.M., Peek, C., Travanty,
E.A., Olson K.E., Brown, S.E., Stephens, J.L., Knudson D.L., Coates C.J., and
James, A.A. (2004). Formation and loss of large, unstable tandem arrays of the piggyBac
transposable element in the yellow fever mosquito, Aedes aegypti.
Transgenic Research 13 411-425
Travanty, E. A., Adelman, Z. N., Franz, A. W., Keene, K. M., Beaty, B.
J., Blair, C. D., James, A. A., and Olson, K. E. (2004) Using RNA interference
to develop dengue virus resistance in genetically modified Aedes aegypti
. Insect Biochem Mol Biol 34 (7) 607-613
Adelman Z.N., Sanchez-
I.
K.E. (2002) RNA silencing of dengue virus type 2 replication in transformed
C6/36 mosquito cells transcribing an inverted repeat RNA derived from the
virus genome. J. of Virology 76 (24) p12925-12933
Olson, K.E., Adelman, Z.N., Travanty, E.A., Sanchez-Vargas,
I.
mosquitoes. Insect Biochem. Mol. Bio. 32, 1333-1343.
Adelman, Z.N., Jasinskiene, N., James, A.A. (2002) Development and
applications of transgenesis in the yellow fever mosquito, Aedes aegypti
. Mol. Biochem. Parisitol. 121(1):1-10
Adelman Z.N., Carlson J.O., Beaty B.J., Blair C.D., Olson K.E. (2001)
Sindbis virus-induced gene silencing of dengue viruses in mosquitoes. Insect.
Mol. Biol. Vol 10 (3): 265-73
Shiao S.H., Higgs, S., Adelman Z., Christensen B.M., Liu S.H., Chen
C.C. (2001) Effect of prophenoloxidase expression knockout on the melanization
of microfilariae in the mosquito Armigeres subalbatus . Insect Mol.
Biol. Vol 10 (4): 315-321.
Blair C.D., Adelman Z.N., Olson K.E. (2000). Molecular strategies for
interrupting arthropod-borne virus transmission by mosquitoes. Clin. Micro.
Rev. 13 (4): 651-661.