H2020Индивидуална стипендия2021–2023

MalariaSex · The molecular mechanisms of sex determination in a malaria parasite

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

Период: 2021-09-01 → 2023-08-31
Финансиране от ЕС: 191 852 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Молекулярните механизми, които определят пола на паразита Plasmodium, се изследват чрез анализ на конкретни гени. Разбирането на тези процеси помага за разработването на нови стратегии за блокиране на предаването на маларията.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

The molecular mechanisms of sex determination in a malaria parasite

Plasmodium parasites are the causative agent of malaria - a severe disease and global health burden with an estimated 241 million cases and 627’000 deaths in 2020. While the clinical symptoms of malaria arise from successive rounds of asexual replication in the blood of the vertebrate host, transmission of the disease to the mosquito vector is facilitated by a small subset of blood-stage parasites entering sexual development. The ability of the parasite to produce fertile female and male gametocytes in an optimal ratio is critical for their reproductive success and disease transmission. Therefore, understanding the molecular mechanisms of sexual development and sex determination in these medically relevant organisms is key to the design of new transmission-blocking strategies and a broader knowledge of how Plasmodium parasites regulate vital life cycle decisions. A recent genetic screen and transcriptomic study have identified a small panel of genes critical for the origin of male gametocytes. Knock-outs of these genes result in skewed gametocyte sex ratios and impact the parasite’s reproduction capacity. However, despite the discovery of genetic factors facilitating sex ratio determination and sexual differentiation, the molecular mechanisms underpinning these processes remain unclear as the functions of the proteins encoded by the identified genes are unknown. This research proposal focuses on uncovering the functions of three maleness-determining candidate genes by applying a combination of biochemical, genetic, and cell biological techniques. The obtained results will elucidate the molecular mechanisms facilitating sex, and thus transmission, of malaria parasites.

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

Цел на проекта

Sexual reproduction is an obligate stage in the complex life cycle of Plasmodium parasites, the causative agent of malaria. While cyclic asexual replication of the parasite in the vertebrate host is associated with all clinical symptoms of malaria, transmission of the disease to a new host relies on sexual reproduction of the parasite in the mosquito. Transmission and reproductive success depend on the ability of malaria parasites to produce fertile male and female gametes at an optimal ratio. Haploid malaria parasites lack sex chromosomes, and sex-ratio is an adaptive and changeable trait to optimize transmission success in response to varying conditions, including multiplicity of infection and immune status of the host. The molecular mechanisms of sexual development hold the key to new transmission blocking interventions and to a broader understanding of how life cycle decisions in an important group of parasites can be regulated. Recent breakthroughs have identified a master regulator for commitment to sexual development, but how one transcription factor can give rise to the completely different gene expression programs of male and female gametocytes has remained elusive. Successful reprogramming experiments and genetic screens in a rodent model have now led to the identification of a small panel of genes, mostly encoding putative nucleic acid binding proteins which I propose here will unlock the question of how sex ratio is determined. By applying a combination of targeted biochemical, cell biological and genetic techniques I aim to characterize the function of three strongly supported, male-determining candidate genes. The obtained results will provide insights into the molecular mechanisms facilitating sex, and thus transmission, of malaria parasites. Moreover, this study will elucidate the fascinating biology of sex determination in an ancient and divergent eukaryote lacking sex chromosomes.

Оригинален текст от CORDIS (на английски).

Участници

UMEA UNIVERSITET · UMEAКоординаторШвеция