H2020Индивидуална стипендия2018–2020

PfPHIST · Characterisation of the Plasmodium PHIST protein family

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

Период: 2018-05-01 → 2020-04-30
Финансиране от ЕС: 177 599 €
Участници: 1
Схема: MSCA-IF-EF-CAR

Линиите свързват координатора с партньорите.

Накратко на български

Протеините от семейство PHIST при паразита Plasmodium falciparum променят структурата на човешките червени кръвни клетки, правейки ги твърди и лепкави. Разбирането на този механизъм помага при разработването на нови ваксини и лекарства срещу малария и разпространението ѝ чрез комари.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Characterisation of the Plasmodium PHIST protein family

Malaria is one of the most devastating human diseases, with almost a third of the world’s population at risk of infection. The most severe form of the disease is caused by Plasmodium falciparum and while there have been considerable efforts to control this parasite, there is still relatively little known about exactly how the parasite causes disease. What is known is that parasite is the ultimate home renovator, and once it has infected human red blood cells it can drastically alter their structure and function, making them rigid and sticky, and in turn cause the more severe malaria symptoms. While the association between these modifications and disease is well described, it has only recently come to light that the parasites capacity to renovate its home may also be important for allowing the parasite to transmit to mosquitoes. The possibility that this ability is vital for both the severity and spread of the disease is incredibly exciting and this is what this project set out to uncover. To begin this task the focus was on one unique family of parasite proteins that we believe could be the Rosetta Stone that finally decodes the mechanisms underlying the parasites ability to renovate the human red blood cells that leads to both severe disease and transmission, with the hope that this information could be used in future vaccine or drug development. The overall conclusion from this project was that the results point to the fact that parasites ability to renovate its home is not only important for disease but also for it spread in the mosquito vector, and as such represent good targets for malaria intervention strategies.

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

Цел на проекта

The malaria parasite is the ultimate home renovator, inducing drastic changes to the host red blood cell (RBC) important for virulence and sexual maturation. Members of the PHIST protein family are involved RBC modification and while some are expressed in the sexual stages, their function is unknown. To understand the significance of the extensive RBC alterations, the functional characterisation of the PHIST family is required. To begin this task, we have carefully selected 10 PHIST proteins to be analysed. First, we will set up novel techniques based on a microfluidics device that will greatly enhance our ability to study the rheological properties of the infected RBC. These new methods will improve our analysis of the infected RBC and also give unprecedented insights into the RBC modifications during the sexual stages, that to date have not been possible. We will also use cutting-edge molecular and biochemical analyses to ensure we get the highest level of data from such a broad and ambitious project. This embodies the first study to thoroughly investigate the role of RBC modifications in parasite virulence, and transmission of the sexual stages to mosquitoes. Dissecting the underlying mechanisms required to alter RBC will not only help to better understand how the disease develops but also how it’s transmitted, information vital to preventing this debilitating disease. This project will lay the foundation to characterise the entire PHIST family, and while this remains the long-term goal, having 75 family members puts this beyond the scope of this fellowship. In order to be able to characterise such a large protein family, a project such as this is required to carefully and precisely establish a pipeline for generating genetic mutants followed by accurate phenotypic analysis. The results obtained in this project will help to reveal the importance of parasite induced RBC structural and functional changes across multiple life cycle stages.

Оригинален текст от CORDIS (на английски).

Участници

STICHTING RADBOUD UNIVERSITEIT · NijmegenКоординаторНидерландия