Elucidating the function of the Lipid-Binding Protein OBI-1 in Pristionchus pacif

描述（由申请人提供）：Pristionchus是一种与特定甲虫相关的线虫，代表了一种鲜为人知但非常普遍的线虫-昆虫相互作用类型，称为necromeny。竖柱线虫维持特定昆虫相互作用的工作模型是通过拦截其宿主昆虫的种内通信。考虑到大量与昆虫和哺乳动物宿主相关的线虫，与甲虫相关的太平洋Pristionchus代表了自由生活模式生物秀丽隐杆线虫和人类丝状线虫（如Brugia malayi和Wucheria bancrofti）之间急需的知识桥梁。这与人类健康尤其相关，因为丝虫病也需要昆虫媒介来传播淋巴丝虫病等疾病。昆虫信息素吸引的分子生理学知识将对我们对线虫嗅觉的理解产生直接影响，这最终可以转化为改进针对寄生虫线虫的治疗方法，寄生虫线虫折磨着全世界约13亿人（世卫组织）。我们最近由美国国立卫生研究院资助的一项研究表明，一种脂质结合蛋白OBI-1通过cGMP信号通路介导宿主昆虫信息素感知，这种信号通路存在于许多动物的感觉细胞中。OBI-1属于一类高度保守但功能多样化的分泌脂质结合蛋白，包括哺乳动物中的脂多糖结合蛋白（lbp）、杀菌通透性增加蛋白（bpi）和胆固醇酯转移蛋白。我们推测，支持化学感觉神经元的神经胶质细胞中OBI-1的表达是线虫嗅觉器官识别甲虫信息素所必需的。我们推测OBI-1可能作为细胞外受体伴侣，引导信息素分子到达膜结合受体，或者作为信号终止器，将信息素从膜结合受体中移除。我们的主要目的是确定OBI-1是否通过神经胶质细胞介导嗅觉，以及OBI-1与信息素分子之间是否存在直接相互作用。我们的长期重点是询问OBI-1在气味感知过程中如何与cGMP途径中的其他因素（如cGMP依赖性蛋白激酶（PKG） EGL-4）进行遗传相互作用。

DESCRIPTION (provided by applicant): Pristionchus species are nematodes that associate with specific beetles and represent a poorly understood but highly prevalent type of nematode-insect interaction known as necromeny. The working model for how Pristionchus nematodes maintain specific insect interactions is by intercepting the intra-species communications of their host insects. Given the multitude of nematode associations with insect and mammalian hosts, the beetle-associated Pristionchus pacificus represents a much needed knowledge bridge between the free-living model organism Caenorhabditis elegans and human filarial nematodes such as Brugia malayi and Wucheria bancrofti. This is especially relevant to human health since filarial nematodes also require insect vectors to transmit diseases such as lymphatic filariasis. Knowledge of the molecular physiology of insect pheromone attraction will have a direct impact on our understanding of olfaction in nematodes, which can ultimately translate into improving treatments against parasitic nematodes that afflict an estimated 1.3 billion people worldwide (WHO). Our recent NIH-funded study revealed that a lipid binding protein, OBI-1, mediates host insect pheromone sensing through the cGMP signaling pathway that is found in many sensory cells of animals. OBI-1 belongs to a class of highly conserved but functionally diverse secreted lipid-binding proteins, including lipopolysaccharide-binding proteins (LBPs), bactericidal permeability-increasing proteins (BPIs), and cholesteryl ester transfer proteins in mammals. We hypothesize that the expression of OBI-1 in the glial cells that support chemosensory neurons is required for the nematode's olfactory organ to recognize the beetle pheromone. We speculate that OBI-1 may act as an extracellular receptor chaperone to guide pheromone molecules to membrane-bound receptors, or as a signal terminator to remove the pheromone from membrane bound receptors. Our primary aims are to determine if OBI-1 mediates olfaction through the glial cells and if there is direct interaction between OBI-1 and the pheromone molecule. Our long-term focus is to interrogate how OBI-1 genetically interacts with other factors the cGMP pathway during odor sensing, such as the cGMP-dependent protein kinase (PKG) EGL-4.