The Insect Vector Project
Anopheles stephensi infected by the fungus Beauveria bassiana (Matt Thomas & Andrew Read)
Population biology of insect vectors
Novel genetic control mechanisms
A homing endonuclease gene (HEG) codes for a protein that, in the heterozygous state, causes a double-strand break in the wildtype chromosome exactly opposite the site where the HEG is inserted. The double-strand break is repaired using the homologous chromosome as a template, and this causes the HEG to be copied from one chromosome to another. The ability to convert a heterozygote to a homozygote leads to very strong selection for the HEG which can quickly rise from very low frequencies to fixation. Austin Burt at Imperial College realised that this was a potentially very powerful technique that could be used to knock out genes in wild populations or to drive beneficial genes to fixation. He brought together a consortium of labs to explore how this might be used to attack the vectors of malaria in Africa which was funded as part of the Gates Grand Challenges in Global Health programme to “Develop a Genetic Strategy to Deplete or Incapacitate a Disease-transmitting Insect Population”. My role is with Austin and the post doc employed on the project, Anne Deredec, to develop population models of the spread of the HEGs and to compare the different ways they might be employed.
We have also worked with Andrea Crisanti and Flaminia Catteruccia at Imperial College, both pioneers of the genetic transformation of Anopheles mosquitoes, to explore the population aspects of mosquito genetic manipulation.
- Alphey, L. & 23 co-authors 2002 Malaria control with genetically manipulated insect vectors (Viewpoint article). Science 298, 119-121.
- Catteruccia, F., Godfray, H.C.J. & Crisanti, A. 2003 Impact of genetic manipulation on the fitness of Anopheles stephensi mosquitoes. Science 299, 1225-1227.
- Deredec, A., Burt, A. & Godfray, H.C.J. 2008 The population genetics of using homing endonuclease genes (HEGs) in vector & pest management. Genetics 179, 2013 – 2026.
Stage-structured population dynamics
We have a long-standing interest in modelling stage-structure in insect populations, particularly in host-pathogen and host-parasitoid interactions where the host is susceptible for only part of its life history. Related stage-structured processes occur in mosquito populations where density-dependence may operate only in the larval stage, while only the adult picks up the malaria pathogen (and this has a fixed maturation period). With Penny Hancock we have been using the lumped age-class technique developed by Roger Nisbit and Bill Gurney to develop a series of mosquito-malaria models in which the full mosquito life cycle is treated in a natural way. We will use these models to help explore strategies for exploiting the HEG genes discussed above.
Currently we are developing models of the adult mosquito stage that treat the gonotrophic cycle (the cycle of blood feeding, egg maturation and maturation) in an intuitive way, and with Matt Thomas models of the interaction between mosquitoes and entomopathogenic fungi that reduce adult mosquito longevity and which might be used as biopesticides.
- Hancock, P.A. & Godfray, H.C.J. 2007 Application of the Lumped Age-Class technique to studying the dynamics of malaria-mosquito-human interactions. Malaria Journal 6, 98.
- Hancock, P.A., Thomas, M.B. & Godfray, H.C.J. 2009 An age-structured model to evaluate the potential of novel malaria control interventions using fungal entomopathogen sprays. Proceedings of the Royal Society of London B 276, 71–80.
Wolbachia are intracellular bacteria that are very common in insects. They are only rarely transmitted horizontally and survive and spread by manipulating their host’s reproduction. The most common strategy they use is cytoplasmic incompatibility. Males carrying Wolbachia in some way modify their sperm such that only females carrying Wolbachia can use them (the modify-rescue model). When Wolbachia infections are common this puts uninfected females (that can’t rescue sperm) at a disadvantage because they can only mate successfully with a subset of males. I have studied Wolbachia distribution in insect communities (failing to find evidence that parasitoids are responsible for rare horizontal transfer).
More recently we have worked on the fascinating dynamics of Wolbachia spread. With Steve Sinkins we have explored what might happen if the rescue function was translocated from the bacteria to the host chromosome. Depending on the costs of the translocation and bacterial carriage the translocation may spread and then drive the Wolbachia to extinction. Was the rescue function to be discovered this offers a potential drive mechanism using Wolbachia that does not involve manipulating the bacteria itself. Since publishing the paper chromosomal transfer of Wolbachia material has been shown to be quite common, and we would predict the genes transferred would include the rescue function. We have also explored how host effects may modify cytoplasmic incompatibility and cause bidirectional incompatibility to break down.
The classic models of Wolbachia suggest there is a threshold Wolbachia frequency above which the bacteria spread and below which it declines to extinction. The threshold is determined by the costs of bacteria carriage, the strength of cytoplasmic incompatibility and the fidelity of bacterial transmission. But in small populations random effects may carry bacterial frequencies above the threshold and allow spread, or vice versa. With Vincent Jansen from Royal Holloway and Michael Turelli from UC Davis we have derived condition for probability of spread in populations of different sizes.
- Hancock, P.A., Sinkins S.P. & Godfray, H.C.J. (in press). Strategies for introducing Wolbachia to reduce transmission of mosquito-borne diseases. PLoS Neglected Pathogens.
- Hancock, P.A., Sinkins S.P. & Godfray, H.C.J. 2011Population dynamic models of the spread of Wolbachia. American Naturalist 177, 323-333.
- West, S.A., Cook, J.M., Werren, J.H. & Godfray, H.C.J. 1998 Wolbachia in two insect host-parasitoid communities. Molecular Ecology 7, 1457-1465.
- Sinkins, S.P. & Godfray, H.C.J. 2004 Utilising Wolbachia to drive nuclear transgenes through insect populations. Proceedings of the Royal Society London, B. 271, 1421-1426.
- Sinkins, S.P., Walker, T., Lynd, A.R. Steven, A.R., Makepeace, B.L., Godfray, H.C.J. & Parkhill, J. 2005. Wolbachia variability and host effects on crossing type in Culex mosquitoes. Nature 436, 257-260.
- Janssen, V.A.A., Turelli, M. & Godfray, H.C.J. 2009. Stochastic spread of Wolbachia. Proceedings of the Royal Society of London B 275, 2769-2776.