Genetics and Genomics of Insect Vectors - CNRS URA3012  


  HEADVERNICK, Kenneth, Ph.D / kenneth.vernick@pasteur.fr
  MEMBERSBISCHOFF Emmanuel, Ph.D., BOURGOUIN Catherine, Ph.D., DUCHEMIN Jean-Bernard, Ph.D., EIGLMEIER Karin, Ph.D., FOUGERE Aurélie, Master 2 student, GARNERO Sylvie, Secretary, GARNIER Thierry, Ph.D., HOLM Inge, Engineer, LAVAZEC Catherine Ph.D., LI Jun, Ph.D, SAUTEREAU Jean, Technician, SOLIS AGUIRRE Carlos, Ph.D.


  Annual Report

Human Malaria

Malaria, caused by protozoan parasites of the genus Plasmodium, is one of the major global infectious diseases. More than 40% of the world population is at risk. Approximately 2 million children die from malaria per year and hundreds of millions of others are sickened by the disease. In addition to the human cost, the economic impact of malaria is also enormous. It is estimated that malaria alone reduces African economic productivity by at least 10%, and thus constitutes a major drag on economic development.

Mosquito Genome Biology

Malaria parasites are transmitted by mosquito vectors in a durable and widespread disease transmission system. As the infected mosquito bites, it injects malaria parasites into the blood, thus initiating a new infection. There is no vaccine against malaria, and although drugs can be effective, the malaria parasite rapidly develops resistance. Because the mosquito is an obligatory vector of the malaria parasite, the chain of transmission can be interrupted by measures that target the mosquito vector. Existing vector control tools such as bednets and insecticide spraying are valuable as part of an integrated attack on malaria transmission by mosquitoes, but they probably cannot do the job by themselves.

Using new genomic research tools, it is now possible to directly query natural populations of mosquitoes and parasites in order to identify mechanisms of vector resistance and immunity against malaria parasites. The GGIV Research Unit bridges the field and laboratory by screening natural vector and parasite populations in Africa to identify genetic mechanisms that can be extracted to the laboratory for genomic, genetic and cellular studies aimed towards developing a new generation of malaria control approaches.

Genetically Resistant Mosquitoes

Why do some mosquitoes exposed to human malaria parasites transmit malaria while other mosquitoes exposed to the same parasites do not transmit the disease? We recently discovered (working with scientists in Africa, Europe, and the US) that a small chromosomal region explains most of the difference in Plasmodium falciparum infection level between individual Anopheles gambiae mosquitoes fed on infected blood. Effectively, many wild mosquitoes are able to kill the malaria parasites they ingest in the blood from an infected person. These naturally resistant mosquitoes break the cycle of malaria transmission, and we found that the same mechanism of resistance probably operates in the vector throughout Africa. A goal of GGIV research is to understand how the resistant mosquitoes kill the malaria parasite, and to develop tools to encourage the spread of the resistant mosquitoes in place of the malaria-transmitting ones.

Transmission-blocking vaccine

We have identified and characterized two genes encoding mosquito midgut carboxypeptidases, and demonstrated that they are involved in the development of P. falciparum in A. gambiae. Several lines of evidence indicate that the A. gambiae midgut carboxypeptidases could constitute components of a vaccine that would block malaria transmission, by reducing Plasmodium development in the mosquito vector and also by reducing levels of vector populations. We are currently determining the biochemical characteristics of these two carboxypeptidases and their role in P. falciparum development, using RNAi as a functional genomics tool.

Germline transformation system

The available methods for establishing transgenic lines in A. gambiae are inefficient and limit extensive genetic analysis in this mosquito species. We are currently establishing a new methodology based on the Phage Phi C31 site specific recombination system in A. gambiae. This system should facilitate the production of mosquito lines with both gain and loss of function for selected genes, such as the A. gambiae midgut carboxypeptidases or genes for resistance to malaria parasites.

Keywords: malaria, mosquito, vector biology, parasitology, host-pathogen interactions



  Publications

Lavazec, C., Boudin, C., Lacroix, R., Bonnet, S., Diop, A., Thiberge, S., Boisson, B., Tahar, R., and Bourgouin, C. (2007). Carboxypeptidases B of Anopheles gambiae as targets for a Plasmodium falciparum transmission-blocking vaccine. Infect Immun 75, 1635-42.

Lavazec, C., and Bourgouin, C. (2008). Mosquito-based transmission blocking vaccines for interrupting Plasmodium development. Microbes Infect 10, 845-9.

Nene, V., … Eiglmeier, K., … and Severson, D.W. (2007). Genome sequence of Aedes aegypti, a major arbovirus vector. Science 316, 1718-23.

Riehle, M.M., Markianos, K., Niare, O., Xu, J., Li, J., Toure, A.M., Podiougou, B., Oduol, F., Diawara, S., Diallo, M., Coulibaly, B., Ouatara, A., Kruglyak, L., Traore, S.F., and Vernick, K.D. (2006). Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region. Science 312, 577-9.

Riehle, M.M., Xu, J., Lazzaro, B.P., Rottschaefer, S.M., Coulibaly, B., Sacko, M., Niare, O., Morlais, I., Traore, S.F., and Vernick, K.D. (2008). Anopheles gambiae APL1 is a family of variable LRR proteins required for Rel1-mediated protection from the malaria parasite, Plasmodium berghei. PLoS ONE 3, e3672.





Activity Reports 2009 - Institut Pasteur
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