Host Cell Remodelling and Sequestration of Malaria Transmission Stages

恶性疟原虫是最严重的人类疟疾，每年造成200多万人死亡。该病的发病率和死亡率可完全归因于在红细胞内居住和复制的无性阶段。这些无性阶段的毒力与恶性疟原虫的独特能力有关，即诱导受感染的红细胞粘附在微血管内皮上，从而避免在脾脏通过时被清除。近年来，人们对无性寄生虫细胞粘附的分子基础和选择压力进行了深入研究，但对幼体传播阶段（即配子体）的隔离却知之甚少。了解性阶段寄生虫在人类红细胞内相对较长的发育过程中的生存策略，是阻断这种破坏性病原体向其蚊子载体传播的新方法的先决条件。该项目将由Matthias Marti监督，旨在更好地了解恶性疟原虫传播中涉及的宿主/病原体相互作用的分子基础。深入了解疟原虫生命周期这一阶段的分子和细胞情况，对于疟疾研究的两项主要任务——开发疫苗战略和新药至关重要。使用一套强有力的最先进的技术，我将解决疟疾传播的基本问题，包括发现和验证新的配子体表面抗原作为潜在的细胞粘附决定因素。我还将确定性阶段寄生虫的体外隔离概况。

Plasmodium falciparum causes the most severe form of human malaria with over two million deaths per year. The morbidity and mortality of the disease can be attributed exclusively to the asexual stages residing and replicating within red blood cells. Virulence of these asexual stages is linked to the unique capability of P. falciparum to induce cytoadherence of infected red blood cells to the microvascular endothelium, thereby avoiding clearance during spleen passage. While the molecular basis and the selective pressures underlying cytoadherence in asexual parasites have been studied intensively in recent years, little is known about sequestration of young transmission stages, i.e. gametocytes. Understanding the survival strategies of sexual stage parasites during their comparatively long development within the human red blood cells is a prerequisite for novel approaches to block the transmission of this devastating pathogen to its mosquito vector. This project will be supervised by Matthias Marti and aims to gain a better understanding of the molecular basis that defines the host/pathogen-interactions implicated in transmission of P. falciparum. Molecular and cellular insights into this phase of the Plasmodium lifecycle are critical to the two major tasks in malaria research, development of vaccine strategies and new drugs. Using a potent set of state-of-the-art techniques, I will address fundamental issues in malaria transmission, including discovery and validation of novel gametocyte surface antigens as potential cytoadherence determinants. I will also determine sequestration profiles of sexual stage parasites ex vivo.