Objective
Plasmodium sporozoites are the motile forms of the malaria parasite injected into the host by a mosquito. Sporozoite motility is essential for tissue penetration as well as host cell invasion and thus pathogenesis suggesting that blocking motility could potentially add a new way in controlling malaria. It is dependent on a parasite specific myosin, a highly divergent actin and plasma membrane proteins, adhesins that link the substrate to the actomyosin motor. We want to understand the molecular and biophysical basis that underlies the motility of sporozoites to eventually be able to block it. Consequently, we developed methods that allow a systematic probing of key variables important in motility in order to reveal the basic mechanisms of sporozoite locomotion and to screen for small molecules that inhibit motility. Using these assays, we made a number of groundbreaking observations on the cellular and molecular level that gave new insights into the mechanisms of sporozoite adhesion and motility. For example, the dynamic, actin-dependent turnover of adhesion sites was found to be a key factor in sporozoite motility. It is our ultimate goal to understand sporozoite motility to a degree that we can provide a comprehensive dynamic model of sporozoite movement. With the current proposal we aim at unravelling the initial molecular events leading to sporozoite motility focussing on three different adhesins that are known or suspected to be involved in motility. We hypothesize that outside-in signalling leading to actin rearrangements originates from the formation of homo- or heterodimers between these adhesins. Additionally we suggest that inside-out signalling contributes to modulation of adhesion strengths mediated by these adhesins. To test these hypotheses we will generate recombinant parasites that lack two adhesins or express fluorescently tagged adhesin fusions, chimeric or mutant adhesins and investigate these with our recently developed toolbox of novel assays.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences health sciences infectious diseases malaria
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences zoology invertebrate zoology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2011-StG_20101109
See other projects for this call
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.
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.
Host institution
69120 HEIDELBERG
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.