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H2020Individual fellowship2015–2017

SECOMAP · Sexual Commitment of Malaria Parasites: Investigation Into the Epigenetic Control of Plasmodium Gametocytogenesis

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-08-01 → 2017-07-31
EU contribution
€195,455
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

Sexual Commitment of Malaria Parasites: Investigation Into the Epigenetic Control of Plasmodium Gametocytogenesis

Despite major efforts to improve prevention and boost treatment malaria is still a major burden for global health. In 2015 the WHO recorded 212 million new cases and 429,000 deaths (http://www.who.int/malaria/publications/world-malaria-report-2016/report/en/). Plasmodium parasites, the causative agent of malaria, alternate between their mammalian host and their mosquito vector. In order to be transmitted to mosquitoes, malaria parasites must develop into gametocytes, which is the only Plasmodium form which can be taken up by mosquitoes in order to initiate a new cycle of infection. In order to maintain the current infection only a small number of parasites circulating in the host’s blood stream undergo gametocytogenesis and develop into gametocytes. Transmission from host to mosquito is considered as a bottle neck in the parasite life cycle, representing a possible target for pharmacological intervention which would disrupt the spread of malaria. However, only little is known about the molecular mechanisms during gametocytogenesis and only recently its master regulator, the transcription factor AP2-G, was identified. AP2-G is believed to be epigenetically silenced in the majority of circulating malaria parasites and only (stochastically) activated in a small number of cells, triggering commitment to gametocytogenesis. The objective of this project was to identify and characterize possible candidate enzymes involved in the epigenetic regulation of Plasmodium development in general, and of ap2-g in particular.

Data: CORDIS, © European Union

Project objective

Malaria is one of the major threats for human health worldwide and caused by unicellular organisms of the Plasmodium genus. Within their mosquito vector and human host malaria parasites replicate almost exclusively asexually. In order to be transmitted to mosquitoes formerly asexual parasites instead develop into gametocytes, which are the only forms that can infect mosquitoes. Understanding the switch of asexual to sexual replication could offer new routes towards therapeutic intervention in sexual development and transmission. However, the molecular details of commitment to gametocytogenesis remain largely unknown, and only recently the AP2-G transcription factor was identified as master regulator of gametocytogenesis.Gametocyte formation is a dead end for enduring infection and therefore sexual commitment has to be suitably regulated to ensure prolonged infection and transmission at the same time. The proposed research project aims to elucidate the epigenetic mechanisms which controls gametocytogenesis in malaria parasites infectious to rodents and humans, and intends to identify key molecular factors which regulate repression and activation of the ap2-g locus. The project will shed new light on the molecular mechanisms controlling sexual commitment and general gene expression in Plasmodium, with implications for therapeutic intervention in transmission and development of malaria parasites.

Original text from CORDIS.

Participants

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Data: CORDIS, © European Union