Mapping of chemosensory neuron function to uncover changes in neuronal fates

项目摘要 全球寄生线虫感染人数超过1.5亿，感染人数高达13亿 人们每年都会从预防性治疗中受益。许多寄生线虫需要 昆虫寄主，在其复杂的生活史中传播给人类寄主。我们使用一种 遗传易驯化的太平洋棱线虫，与昆虫有关，是一种 研究如何从有限的神经元集合中产生不同行为的比较模型。 我们提出的研究解决了一个基本问题，即神经系统如何 进化以适应新的行为，特别是如何以及哪些转录因子 来指定宿主中化学感觉神经元的发育命运- 寻求行为。我们将使用反向遗传学来定位候选转录 被称为末端选择器基因的因子，以及可诱导的转基因敲击 在单细胞水平上下调神经元功能。我们还将使用正向遗传学来 不偏不倚地研究哪些基因对口味偏好的改变起作用 当线虫发育成生殖成虫或寻找寄主时，它们会闻到 感染性幼虫。详细了解神经元重塑是如何影响的 化学感觉可以揭示在不同物种中发现的感觉神经元的基本蓝图 线虫，它可以提供中断寄生线虫传播的方法 在昆虫和人类宿主之间。

Project Summary Parasitic nematodes infect more than 150 million people worldwide and up to 1.3 billion people benefit from preventative treatment annually. Many parasitic nematodes require insect hosts for transmission to human hosts in their complex life cycles. We use a genetically tractable nematode Pristionchus pacificus that is associated with insects as a comparative model to study how diverse behaviors arise from a limited set of neurons. Our proposed research addresses a fundamental question on how nervous systems evolve to accommodate new behaviors, specifically how and which transcription factors are required to designate the developmental fates of chemosensory neurons in host- seeking behavior. We will use reverse genetics to target candidate transcriptional factors, known as terminal selector genes, as well as inducible transgenes to knock down neuronal function at the single cell level. We will also use forward genetics to investigate unbiasedly which genes are responsible to switch the preferences for taste and smell when the nematodes develop into reproductive adults or host-seeking infectious larvae. A detailed understanding of how neuronal remodeling affects chemosensation could reveal the basic blueprint for sensory neurons found in diverse nematodes, which could inform ways to disrupt the transmission of parasitic nematodes between insect and human hosts.