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A hybrid framework to characterize SLiM Mimicry by Leishmania (SMILE) parasites.

Project description

Leishmania protein motifs as disease determinants

Leishmaniasis is a chronic infection that affects millions of individuals worldwide each year, but the host–pathogen interaction remains unresolved. SMILE is an EU-funded initiative that aims to understand how eukaryotic pathogens such as Leishmania invade and take over cells. Researchers will employ computational methods to study the host–pathogen interaction at the molecular level. Their focus will be on pathogen protein sequences known as short linear motifs (SLiMs) and their role in disease. Identification of SLiMs on Leishmania proteins will fuel further research down unexplored paths and may lead to novel therapeutic strategies.

Objective

Pathogens invade and colonize their target host by modulating several key processes of host cells, resulting in modified physiology. Interference mechanisms are intensively studied in the case of viruses and bacteria, however, our knowledge about invasive eukaryotic pathogens is more limited.
To understand how eukaryotic pathogens hijack host processes at the molecular level, Leishmania will be examined using computational methods and the results will be validated by experimental techniques. Leishmaniasis is a parasitic protozoan disease, responsible for non-resolving and chronic infection, affecting over 10 million people worldwide. Ongoing environmental changes are considered to be helping the disease to spread to new regions. Leishmania pathogenesis is poorly understood and to combat the infection and to control the disease, further insights into host-pathogen interaction are desperately needed.
An integral part of the constant arms race between the host immune system and pathogens is the rapid evolution of pathogenic Short Linear Motifs (SLiMs), capable of modulating the host cell regulation. The limited sequence length of these protein-binding segments provides evolutionary advantages for the pathogen, as SLiMs can arise de novo and many can be packed into a single protein. Their properties make them hard to explore using biochemical methods alone, however, using bioinformatics approaches this process can be accelerated.
SMILE aims to identify SLiMs mediating Leishmaniasis. My hierarchical strategy starts from protein level identification to detailed structural characterisation of host-pathogen interactions, as an ultimate goal. The description of SLiMs already suggests novel therapeutic strategies to counteract mutation-based diseases.  The outcome of the project has the potential to suggest targets for the development of similar treatments against eukaryotic parasitic diseases.  

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 162 806,40
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost

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.

€ 162 806,40
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