MALVECBLOK

Population biology and molecular genetics of vectorial capacity in Anopheles gambiae: targeting reproductive behaviour and immunity for transmission-refractory interventions

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 Obiettivo del progetto (Objective)

'Malaria, one of the world’s most devastating diseases, is caused by protozoan parasites of the genus Plasmodium and is obligatory transmitted to humans by anopheline mosquitoes. The African mosquito species Anopheles gambiae s.s., is the major vector of this disease. Research groups from 3 European countries and 3 African teams will integrate their resources and scientific expertise in malaria research to expand knowledge of mosquito biology and of vector-parasite interactions, exploiting the opportunities provided by the recently available genome information and technological developments for mosquito vectors. The joint scientific program of the MALVECBLOK Consortium integrates for the first time three crucial aspects of biology of An. gambiae: reproduction, immunity and population biology, with the aim to ultimately provide novel concepts and targets for malaria control. The main objectives will address: (i) The molecular bases of reproductive biology of the mosquito vector, and its effects on immunity and Plasmodium transmission; (ii) The molecular mechanisms which determine the mosquito immune status and regulate Plasmodium sporogony and transmission, in both laboratory settings and natural populations; (iii) The role of genetic polymorphism in genes controlling reproduction and immunity on structure of mosquito populations and malaria transmission in Africa. In order to reach these objectives, MALVECBLOK will employ a number of concerted strategies in support of its 3-year agenda. Special attention will be given to cutting-edge training opportunities and sharing of resources, by implementing interactive programmes for the training and exchange of personnel at all levels, and by rationalising and coordinating investment. The innovative knowledge generated under this trans-disciplinary project will promote European scientific competitiveness and will impact global health issues.'

Descrizione progetto (Article)

Malaria is a parasite disease caused by Plasmodium falciparum and transmitted mainly through Anopheline mosquitoes acting as vectors. The emergence of parasite resistance to existing anti-malaria drugs has prompted scientists into finding novel control measures.

Based on this, African and European researchers of the EU-funded MALVECBLOK project investigated how mosquito reproduction and immunity could affect malaria transmission. The idea was to identify molecular targets that could help them shape the mosquito populations in malaria endemic regions, thereby blocking parasite transmission.

To this end, the consortium studied the molecular basis of mosquito reproductive biology with particular emphasis on characterising the composition of the mating plug. By genetically engineering infertile mosquitos depleted of sperm, scientists evaluated the post-mating responses and reproductive success in the malaria mosquitoes. They discovered a connection between responses of females to mating and to blood feeding that was associated with the activation of certain genes.

Work on the molecular mechanisms that shape mosquito immune status revealed that the anti-parasitic gene telomerase protein component 1 (TEP1) is activated after mating, among other immune-related genes. Results showed that the TEP1/ leucine-rich repeat (LRR) complex mediated the defence against bacteria and malaria parasites.

An equally important determinant of the mosquito anti-parasite action was the genetic diversity of P. falciparum, which enabled parasites to survive the vector immune responses. Genotyping of the mosquito gene TEP1 showed that the variant that confers resistance to Plasmodium is distributed in certain parts of Africa. This finding could infer important information regarding disease spread. Transmission of malaria was also found to correlate with the presence of certain microbiota like enterobacteria in mosquito vectors. This constitutes another region-specific factor that may contribute to malaria transmission in Africa.

The MALVECBLOK initiative elucidated the molecular events involved in reproduction and immunity of the mosquito, and identified environmental factors that may influence disease spread. Taken together, the project findings provide new concepts for innovative vector measures to control malaria transmission.