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Regulation of sexual development in malaria parasites - and the design of logical intervention strategies

Objective



We will investigate the developmental regulation of the sexual stages of plasmodium spp. at the molecular level, and in lab and field studies will analyse immunological principles regulating the infectivity to the mosquito vector. This ambitious and wide ranging programme is possible only because of the extensive collaboration between the numerous scientists in this network. We will study the human parasites P. falciparum and P.-Vivax' and, Where appropriate the rodent parasite P. berghei.--The network-has established a unique combination of in vivo and in vitro techniques for P.-berghei which has permitted the extensive characterization of the biology and molecular regulation of the sexual stages. We have selected 4 interesting and fundamental leads generated in the STD2 programme for further study, these are:-
1. The regulation of gametocytogenesis:- a). Identification of the population dynamic principles - and environmental inducers triggering the switch from asexual to sexual development. b). The karyotypic organisation of plasmodium vivax, and in particular, also of gametocyte producing clones vs non-producing clones of P. Berghei and P.-falciparum. 2. The regulation of sexual stage gene expression:- A substantial and far reaching analysis of the mechanisms of regulation of gene expression and the cell cycle both in the maturing gametocyte and during transition of gametocyte to ookinete stages of malaria during mosquito infection.
3. The biology of parasite transmission:- Analysis of the
population dynamic principles underpining the regulation of infectivity of gametocytes to the mosquito vector in P.-Berghei and its molecular regulation. This study will be closely correlated with separately funded lab and field studies on P. falciparum and P. vivax.
4. Transmission blocking immunity:- We will complete the molecular cloning of available transmission-blockina antigens and characterize new
potential targets in P. vivax and P. falciparum; define the relevant mechanisms of transmission blockade; examine the natural immune response inducible both in vivo and in vitro; and determine how the immune status of the individual may moderate responses to the sexual-stage

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
Address
Campus At Silwood Park, Road A329 (Virginia Water
SW7 2AZ London
United Kingdom

Participants (3)

Instituto Nacional de Salud - Secretaria de Salud
Mexico
Address
4A Av. Norte Esq. Con 19 Poniente
30700 Tapachula Chiapas
Istituto Superiore di Sanità
Italy
Address
Viale Regina Elena 299
00161 Roma
LEIDEN UNIVERSITY
Netherlands
Address
62,Wassenaarseweg 62
2300 RC Leiden