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Content archived on 2024-06-18

Monoallelic Gene Expression in Malaria Parasites: A Key Mechanisms in the Pathogen's Survival Strategy

Objective

An important number of human and animal pathogens use antigenic variation of surface proteins as a mechanism to avoid destruction by the host s immune system. Most escape mechanisms rely on the successive expression of members of gene families in a mutually exclusive manner, a biological process which remains elusive at the molecular level. The protozoan pathogen Plasmodium falciparum, which infects up to 300 million people causing more than two million lives each year, undergoes antigenic variation to establish chronic blood stage infection. A critical determinant in chronic infection and pathogenesis is the expression of clonally variant molecules at the surface of infected erythrocytes. Several variant gene families undergo antigenic variation in P. falciparum and are expressed during blood stage infection. One family encoded by 60 var genes expresses the most well-known virulence factor causing severe malaria (capillary blockages in the brain and other organs mediated by infected erythrocytes). Switching expression between the 60-member var gene family avoids immune clearance and prolongs the period of infection and transmission to the mosquito. The initial event controlling mono allelic expression at a unique expression site remains elusive and represents the Holly Graal in the field of phenotypic variation. To this end, the major objective of this proposal is to identify specific factors contributing to active expression sites (proteins, DNA enhancer or ncRNA) by using novel strategies such as Proteomics of Isolated Chromatin segments (PICh) and Chromosome Conformation Capture (3C). We expect that new insights into the underlying principles of gene counting of virulence gene families may reveal an Achilles Heel of the parasite s immune evasion strategy.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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ERC-2009-AdG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-AG - ERC Advanced Grant

Host institution

INSTITUT PASTEUR
EU contribution
€ 1 815 480,00
Address
RUE DU DOCTEUR ROUX 25-28
75724 Paris
France

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Region
Ile-de-France Ile-de-France Hauts-de-Seine
Activity type
Research Organisations
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Total cost

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Beneficiaries (1)

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