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Regulation of development in malaria parasites

Objective

* The investigation of the regulation of parasite development through studies on 1) gene promotor structure, strength and stage specificity and on 2) function of the proteins encoded by the genes under the control of these promoters.

* The genes of study are: P. falciparum, Glycophorin binding protein (GBP) 130, Na+/H+ transport protein; from P. berghei, PBS21, pbB7, rRNA units (A-D), 150 family, crk2, EF-1a; from P. vivax, crk2, EF-1a, rRNA.

* Development of plasmid systems based upon the Tet repressor which will allow the inducible expression of cloned genes in different species of Plasmodium.

* Where feasible, to develop resources to facilitate the isolation and characterisation of genes encoding proteins with a specific role in development during gametocytogenesis and throughout the mosquito phase of the life cycle in P. vivax and P. berghei.
Expected Outcome

* The programme should provide a functional analysis of the genes under study and thus provide insights into their role during the complex development cycle of Plasmodium.

* An insight will be gained into the functional structure of stage specific promoters of gene transcription. This can be expected to include an identification of those elements which dictate stage- and sex-specificity and those which direct basal transcription.

* The study will provide reagents and materials, which are essential for further studies on the sexual development of Plasmodium.
* Where appropriate, to clone and complete the full characterisation of the named genes, their sequence, expression and comparative structures.

* Studying the structure and function of promoters of transcription of RNA polymerases I and II in both P. berghei and P. falciparum using stable and transient transfection technologies.

* Investigating the species specificity of promoter structure through an investigation of the ability of defined promoter regions of genes isolated from P. vivax to accurately control transcription in P. berghei.

* Developing plasmid systems based upon the Tet repressor which will allow the inducible expression of cloned genes in different species of Plasmodium.

* Initiating a study of structure/function relationships of specific parasite structures through gene mutagenesis, replacement, over-expression and/or knock out to establish the role of the protein.

* Studying the control of gene expression in P. berghei at the post-transcriptional level in female gametocytes using the Pbs21 (female gametocyte specific), 150 gene family (variant 3' UTR) and pbB7 (nuclear protein gene) as paradigms.

* Where feasible developing resources to facilitate the isolation and characterisation of genes encoding proteins with a specific role in development during gamecytogenesis and throughout the mosquito phase of the life cycle in P. vivax and P. berghei.

* To continue to expand the investigation of the relationship between genome organisation and sexual development.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

LEIDEN UNIVERSITY
Address
62,Wassenaarseweg 62
2300 RC Leiden
Netherlands

Participants (5)

Bayerische Julius-Maximilians-Universität Würzburg
Germany
Address
11,Röntgenring 11
97070 Würzburg
Istituto Superiore di Sanità
Italy
Address
Viale Regina Elena 299
00161 Roma
UNIVERSITAETSKLINIKUM HEIDELBERG
Germany
Address
Im Neuenheimer Feld 324
69120 Heidelberg
Universidad del Valle de Guatemala
Guatemala
Address
Apartado Postal
1901 Guatemala City
Universidade de São Paulo
Brazil
Address
1374,Avenida Prof. Lineu Pretes 1374
5508 São Paulo