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

Descrizione del progetto

Sequenze proteiche della Leishmania come fattori determinanti di malattia

La leishmaniosi è un’infezione cronica che colpisce ogni anno milioni di persone in tutto il mondo, ma l’interazione ospite-patogeno rimane irrisolta. SMILE è un’iniziativa finanziata dall’UE che intende comprendere in che modo gli agenti patogeni eucariotici come la Leishmania colonizzano le cellule e si sostituiscono a loro. I ricercatori impiegheranno metodi computazionali per studiare l’interazione ospite-patogeno a livello molecolare, ponendo l’attenzione sulle sequenze proteiche degli agenti patogeni, note come brevi motivi lineari (SLiM, Short Linear Motif), e sul loro ruolo nella malattia. L’identificazione dei brevi motivi lineari nelle proteine della Leishmania stimolerà la conduzione di altre ricerche lungo percorsi inesplorati e potrebbe portare a strategie terapeutiche innovative.

Obiettivo

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.  

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

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

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Invito a presentare proposte

(si apre in una nuova finestra) H2020-MSCA-IF-2020

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Coordinatore

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Contributo netto dell'UE
€ 162 806,40
Indirizzo
Meyerhofstrasse 1
69117 Heidelberg
Germania
Regione
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 162 806,40