Genetics and Genomics of Insect Vectors - CNRS URA3012  


  HEADVERNICK, Kenneth, Ph.D. / kvernick@pasteur.fr
  MEMBERSBOURGOUIN Catherine, Ph.D., EIGLMEIER Karin, Ph.D., FOUGERE Aurélie, Master 2 student, GARNERO Sylvie, Secretary, GARNIER Thierry, Ph.D.
HOLM Inge, Engineer, LI Jun, Ph.D, SAUTEREAU Jean, Technician


  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 the mosquito, A. gambiae. Antibodies directed against one carboxypeptidase strongly reduce the efficiency of development within the mosquito of the malaria parasites, P. falciparum and P. berghei, and also reduce mosquito fecundity. Therefore, 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.

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



  Publications

Boisson, B., Jacques, J.C., Choumet, V., Martin, E., Xu, J., Vernick, K., and Bourgouin, C. (2006). Gene silencing in mosquito salivary glands by RNAi. FEBS Lett 580, 1988-92.

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.

Li, J., Riehle, M.M., Zhang, Y., Xu, J., Oduol, F., Gomez, S.M., Eiglmeier, K., Ueberheide, B.M., Shabanowitz, J., Hunt, D.F., Ribeiro, J.M., and Vernick, K.D. (2006). Anopheles gambiae genome reannotation through synthesis of ab initio and comparative gene prediction algorithms. Genome Biol 7, R24.

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.





Activity Reports 2007 - Institut Pasteur
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