H2020Индивидуална стипендия2021–2023

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-08-01 → 2023-07-31
Финансиране от ЕС: 162 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Паразитът Leishmania използва кратки протеинови сегменти (SLiMs), за да имитира функции на клетката на гостоприемника и да заобиколи имунната система. Разбирането на тези взаимодействия помага за разработването на нови стратегии за борба с това заболяване.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Pathogens are microorganisms that invade and take over their target host's body by manipulating the host's immune system and suppressing its defenses. This results in changes to the host's normal functions and physiology. They interfere with various cellular processes, such as transport, replication of DNA, to ensure their survival and reproduction. We know a lot about how viruses and bacteria do this, which has led to the development of targeted treatments. However, our understanding of invasive eukaryotic pathogens is still limited. To gain insights into how eukaryotic pathogens hijack host cells, we focused on Leishmania. Leishmaniasis is a parasitic disease caused by Leishmania, affecting millions of people worldwide, with annual deaths estimated to range from 26,000 to 65,000. While it mainly affects impoverished and rural areas, environmental changes could lead to its spread in new regions. Understanding Leishmania's behavior and how it interacts with the host's cells is crucial to develop ways to combat the infection and control the disease. In the constant battle between the host's immune system and pathogens, pathogenic Short Linear Motifs (SLiMs) play a significant role. These small segments of proteins have the ability to modulate the host cell's functions and evolve rapidly, giving the pathogen an advantage. Studying SLiMs using traditional methods is challenging, but bioinformatics approaches can accelerate the process. The proposed project aims to systematically examine interactions at the protein level and understand the structural details of these interactions. This information can be used by experimentalists to identify linear motifs, which could lead to new therapeutic strategies for mutation-based diseases. Understanding how Leishmania invades and mimics host cell functions is a critical step toward developing treatments for parasitic diseases. In conclusion, this research aims to uncover the strategies used by eukaryotic pathogens, specifically Leishmania, to take control of host cells. By understanding these mechanisms, scientists hope to develop targeted treatments and combat parasitic diseases more effectively.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergКоординаторГермания