Purchase of an automated "tipper" system to support the culture of infectious gametocytes for experimental malaria mosquito infections

我们正在请求提供支助，以购买三个“自动培养”系统，用于自动培养蚊子传播的疟疾寄生虫。疟疾仍然是一种由疟原虫寄生虫引起的对全球健康具有毁灭性影响的疾病。疟原虫通过蚊子叮咬传播，具有复杂的生命周期，涉及转化为几种不同的形式，这些形式专门用于不同的角色。近半个世纪以来，科学家们一直能够在实验室中培养恶性疟原虫（导致最致命的疟疾）。大多数科学研究都集中在寄生虫生命周期的无性阶段，因为这是导致疾病症状并且容易生长的阶段。然而，为了传播给蚊子，寄生虫必须转化为配子体。配子细胞在实验室中生长更具挑战性，因为它们需要14天的时间才能发育，需要研究人员每天“喂养”它们，并且永远不要让它们从体温中冷却。这意味着它们通常是小批量连续种植的，这消耗了大量的时间，否则研究人员将不得不专注于实验。实验性蚊子传播需要使用寄生虫培养设施、饲养蚊子的昆虫和进行蚊子感染的设备和熟练的工作人员。利用LSHTM的这些独特资源，我们建立了人类疟疾传播设施，为英国和全球疟疾社区提供服务，为没有专门设施的研究人员提供实验性蚊子感染。该设施正在成功地支持一系列项目，但人工配子母细胞生产的瓶颈限制了进一步扩大。荷兰的另一个传播设施采用称为“tippers”的定制培养系统来自动化每天的配子体喂养，这显著减少了常规培养维护，并为实验保持了一致的高质量寄生虫。购买一个类似的系统将为LSHTM设施提供类似的吞吐量增益，并释放额外的实验时隙，使我们能够支持更大范围的传输项目。

We are requesting support to purchase three "tipper" systems for automated culture of malaria parasites for mosquito transmission. Malaria is still a disease of devastating impact to global health caused by the parasite Plasmodium. Plasmodium is transmitted by the bite of a mosquito and has a complex life cycle which involves transforming into several distinct forms which are specialised for different roles. Scientists have been able to culture Plasmodium falciparum (which causes the most deadly forms of malaria) in the laboratory for almost half a century. Most scientific research is focused on the asexual stage of the parasite life cycle, as this is the stage that causes disease symptoms and is easy to grow. However, to transmit to mosquitoes, the parasite must transform into gametocytes. Gametocytes are much more challenging to grow in the laboratory as they require 14 days to develop, requiring the researcher to "feed" them daily and never let them cool from body temperature. This means that they are usually laboriously grown in small batches continuously which consumes a lot of time that researchers would otherwise have to focus on experimentation. Experimental mosquito transmission requires access to parasite culture facilities, insectaries to rear mosquitoes and the apparatus and skilled staff to perform the mosquito infection. Taking advantage of these unique resources at LSHTM, we established the Human Malaria Transmission Facility to serve the UK and global malaria community providing researchers without specialised facilities, access to experimental mosquito infection. The Facility is successfully supporting a range of projects, however a bottleneck in manual gametocyte production is limiting further expansion. Another transmission facility in the Netherlands employs bespoke culture systems called "tippers" to automate the daily gametocyte feeding which significantly reduces routine culture maintenance and maintains consistent high quality parasites for experimentation. Purchase of a comparable system will give similar throughput gains for the LSHTM Facility and release additional slots for experimentation and allow us to support of a greater range of transmission projects.