Influence of temperature on malaria transmission and prospective vector control

描述（由申请人提供）：最近的研究使我们对蚊子-疟疾寄生虫相互作用的机制理解取得了重大进展，并产生了许多可能在未来媒介控制中发挥作用的新方法。绝大多数研究都是在标准化的昆虫条件下进行的。然而，蚊子和寄生虫在一个多变的世界里联系在一起。我们在当前提案中的总体目标是确定实验室和现场条件之间的这种不匹配是否有影响。具体来说，我们的目标是确定环境温度的实际变化在多大程度上影响蚊子-寄生虫相互作用的结果，以及两类潜在控制工具的可能影响。我们将首先量化不同温度（包括恒温和实际的每日温度变化）对一组蚊子（斯氏按蚊）和寄生虫（恶性疟原虫）特征的影响，这些特征结合起来决定疟疾传播强度。为了补充这些表型测量并探索温度对蚊子和寄生虫生理的机制影响，我们将使用RNA测序来鉴定蚊子和寄生虫的转录本，这些转录本与蚊子和寄生虫随环境温度和感染状态变化而变化的特征密切相关。然后，我们将使用qRT-PCR在更精细的尺度上检查关键蚊子和寄生虫基因的表达动态在整个感染过程和一系列环境温度处理中是如何变化的。在这些基线数据的基础上，我们将扩展研究，以评估温度对一种真菌病原体的毒力的影响，这种真菌病原体目前正在开发中，用作对抗成年疟疾病媒的生物农药，以及阻断疟疾传播的潜力

DESCRIPTION (provided by applicant): Recent research has led to significant advances in our mechanistic understanding of mosquito-malaria parasite interactions, and yielded a number of novel approaches that could play a role in future vector control. The vast majority of this research has been conducted under standardized insectary conditions. Yet mosquitoes and parasites associate in a variable world. Our overall objective in the current proposal is to determine whether this miss-match between lab and field conditions matters. Specifically we aim to determine the extent to which realistic variation in environmental temperature affects the outcome of the mosquito-parasite interaction and the likely impact of two classes of prospective control tools. We will begin by quantifying the effects of different temperatures (both constant temperatures and realistic daily temperature variation) on a suite of mosquito (Anopheles stephensi) and parasite (Plasmodium falciparum) traits that combine to determine malaria transmission intensity. To complement these phenotypic measures and explore the mechanistic effects of temperature on mosquito and parasite physiology, we will use RNA sequencing to identify mosquito and parasite transcripts that correlate most strongly the mosquito and parasite traits that vary with changes in environmental temperature and infection status. We then will use qRT-PCR to examine at a finer scale how the expression dynamics of key mosquito and parasite genes change throughout the course of infection and across a range of environmental temperature treatments. Building on these baseline data, we will extend studies to evaluate the effects of temperature on the virulence of a fungal pathogen currently being developed for use as a biological pesticide against adult malaria vectors, and the transmission blocking potential of mosquitoes genetically modified to express novel anti-parasitic transgenes. Finally, we will use a suite of modeling approaches parameterized from the novel empirical data to explore the implications of environmental temperature for malaria transmission and control. Combined, the research will advance fundamental understanding of mosquito immune function and vector competence, better characterize the overall role of environmental temperature in the dynamics and distribution of malaria and provide an evidence base for appropriate development of innovative vector control tools.