PROJECT DESCRIPTION:
Selfish genetic elements have been studied for over a century, and as
far back as the 1960’s researchers became interested in using the power of
selfish genetic elements to drive genes into pest species to suppress their
impacts (Gould et al. 2006). Until recently, the focus of applied work was
on naturally occurring elements. In the past decade some progress was made
on developing synthetic elements that mimicked natural meiotic drive and
selective embryo-killing, but de-novo creation of a gene-drive system in a
pest species was elusive. With the harnessing of the bacterial CRISPR-Cas9
system in the past few years there has been a revolution brewing in this
field (Esvelt et al. 2014, Oye et al. 2014). In March 2015 a pivotal article
by Gantz and Bier (2015) came out in Science on-line demonstrating a
CRISPR-Cas9 construct in Drosophila with strong gene drive. This proof of
principle has gained much attention.
Prospects are good that very soon a single student could
engineer a system for driving deleterious or behavior modifying genes into
pest populations. Not everyone is comfortable with these developments and
there has even been a call for a moratorium on certain experiments. There
are also concerns about nefarious use of the technology.
The bottom-line is that progress in molecular biology is ahead
of the population genetic work needed to build systems that are less risky
but accomplish changes in the public interest.
We have been funded by the NIH and the W. M. Keck Foundation
to conduct this kind of population genetic research. Our focus has been on
mosquitoes that transmit dengue and malaria, but we are also interested in
other biological systems (There is hope that these selfish genetic elements
can save endangered species like Hawaiian honeycreepers and specific
seabirds (Gould 2008, Esvelt et al. 2014).
The postdoc in this position will build a set of simple to
complex models to examine the expected dynamics of gene drive systems in
mosquitoes and other taxa.
The most detailed model that we have developed simulates the
population dynamics and population genetics of Aedes aegypti, the vector of
dengue, in a city on the Amazon river, Iquitos, for which there are rich
data sets on both mosquito dynamics and dengue epidemiology (e.g. Magori et
al. 2009, Okamoto et al 2014). An accompanying epidemiological model is
currently under development. The goals of two other postdocs in our group
are to expand the mosquito model and the human epidemiology model to
encompass the entire city of about 400,000 people. The postdoc in this new
position will collaborate with the other postdocs to use these detailed
models to test gene drive systems, but will also develop more generic models
(e.g. Huang et al. 2010).
In addition to working on model development and analysis, the
person in this position will have the opportunity to collaborate in an
interdisciplinary research group composed of mosquito ecologists, disease
epidemiologists, molecular biologists, biomathematicians, ethicists, and
scientists from disease-endemic countries. We are dedicated to taking
seriously the ethical and political issues surrounding this technology.
DESIREABLE SKILLS: A background in population genetics and the ability to
program in C++ (or knowledge of a related programming language), and
training in evaluation of mechanistic models.
TO APPLY: email a cover letter and CV to [email protected]
References:
Esvelt, K. M., A. L. Smidler, F. Catteruccia, G. M. Church. 2014.
Concerning RNA-guided gene drives for the alteration of wild populations.
eLife. 10.7554/eLife.03401.
Gantz, V. M. and Bier, E. 2015. The mutagenic chain reaction: A method for
converting heterozygous to homozygous mutations. Science 24 April 2015-
442-444. Published online 19 March 2015 [DOI:10.1126/science.aaa5945]
Gould, F. 2008. Broadening the application of evolutionarily based genetic
pest management. Evolution 62: 500–510.
Gould, F., K. Magori, Y. X. Huang 2006 Genetic strategies for controlling
mosquito-borne diseases. American Scientist. 94 (3): 238- 246.
Huang, Y., Lloyd, A.L., Legros, M., Gould, F. 2010. Gene-drive into insect
populations with age and spatial structure: a theoretical assessment. Evol.
Appl. ISSN 1752-4571.
Magori, K., M. Legros, M. Puente, D. A. Focks, T. W. Scott, A. Lloyd, F.
Gould. 2009. Skeeter Buster: a stochastic, spatially-explicit modeling tool
for studying Aedes aegypti population replacement and population suppression
strategies. PLoS Negl Trop Dis 3(9): e508. doi:10.1371/journal.pntd.0000508
Okamoto, K. W., Robert M. A., Gould, F., Lloyd, A. L.2014) Feasible
Introgression of an Anti-pathogen Transgene into an Urban Mosquito
Population without Using Gene-Drive. PLoS Negl Trop Dis 8(7): e2827.
doi:10.1371/journal.pntd.0002827.
Oye, K. A. et al. 2014. Regulating gene drives. Science. 345:626-628
Published online 17 July 2014
