Elucidating the molecular mechanism underlying regulation of heterochromatin dissociation in human malaria parasite

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15449
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Osaka University
• Principal Investigator: Nakashima Mai 大阪大学, 微生物病研究所, 特任助教(常勤) (50911319)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: マラリア / 転写制御 / エピジェネティクス / 寄生虫

Outline of Final Research Achievements

Plasmodium falciparum, a causative agent of human malaria, is a unicellular parasite that reproduces asexually during the intraerythrocytic cycle. A small fraction of them develops into gametocytes, the sexual form critical for transmission from human to mosquito vector. Gametocytogenesis is triggered by a single master regulator, AP2-G. AP2-G is a transcription factor, and its transcription is strictly repressed by heterochromatinization of the gene locus, although the fundamental mechanism of AP2-G regulation has remained elusive. In this study, we tried to identify a sequence element in the heterochromatinized AP2-G promoter that participates in chromatin dissociation leading to AP2-G expression, using in vivo reporter system in which artificial chromosome vectors carrying AP2-G promoter, coding region and terminator are introduced into AP2-G-deleted parasite.　As a result, we identified a unique sequence required for the maintenance of chromatin condensation on the reporter.

Free Research Field

寄生虫学

Academic Significance and Societal Importance of the Research Achievements

今回、独自に開発した技術であるin vivoレポーターシステムを用いてマラリア原虫の転写制御評価系を確立したことは、将来的に未だ未知のヘテロクロマチン制御機構を分子レベルで解明することに繋がる。また、本研究はAP2-Gを通じたマラリア原虫の性分化のエピジェネティックな発現制御機構に新たな知見を加えるだけでなく、抗原転換による宿主免疫回避機構の解明の糸口となり、ひいてはこの機構を標的とした新規ワクチンの開発や創薬などマラリアの予防・治療を目指した医療応用研究に新たな道を拓くものである。