Elucidate C. elegans Oxygen Sensing with Microfluidics

描述（由申请人提供）： 氧传感在代谢和许多疾病相关过程中是重要的，例如缺氧和血管生成。本课题的目的是研究C.优雅C.秀丽隐杆线虫是一个很好的模型系统，因为它是一种简单的多细胞生物，具有强大的分子和遗传工具。然而，目前C.由于技术上的困难，线虫行为研究限制了可以进行的实验类型和对某些结果的解释。微流体有助于解决这些技术挑战，并可以通过定量评估行为来推进这些研究。在这个项目中，将开发可靠的微流体氧气输送系统，以测定蠕虫对特定氧气浓度或梯度的反应。将使用适当的数学模型来设计这些装置，并将探索使用生物相容性和透氧性聚合物材料的微制造工艺。 这些工具允许使用在四个潜在重要的感觉神经元中缺乏特定功能的突变体对神经回路进行定量研究。该试验将探索这些神经元是否以及如何定义氧偏好的特异性。此外，本研究将阐明氧偏好是否是一个适应性过程，在此过程中，生物体可能会改变其代谢，以适应环境。一类鸟苷酸环化酶在传感和行为中的作用也将被研究，以及与经典转录途径的可能联系。这种类型的分析只能通过精细控制的氧气输送系统进行。这项研究中开发的一般技术应该会影响其他C。elegans研究的感觉和行为，如气味辨别和温度感觉。

DESCRIPTION (provided by applicant): Oxygen sensing is important in metabolism and many disease-related processes, such as hypoxia and angiogenesis. The goal of this project is to study the mechanisms of and neurons involved in oxygen sensing in C. elegans. C. elegans serves as an excellent model system because it is a simple multicellular organism with powerful molecular and genetic tools available. However, current approaches for C. elegans behavior research limit the type of experiments that can be performed and the interpretation of some results due to technical difficulties. Microfluidics lends itself in solving these technical challenges and can advance these studies with quantitative assessment of behaviors. In this project, reliable microfluidic oxygen delivery systems that assay worms' response to specific oxygen concentrations or gradients will be developed. Appropriate mathematical models to design these devices will be used, and microfabrication processes using biocompatible and oxygen permeable polymer materials will be explored. These tools allow the quantitative investigation of the neural circuitry using mutants that lack specific functions in four potentially important sensory neurons. The assay will probe whether and how these neurons define the specificity of oxygen preference. Furthermore, this study will elucidate whether oxygen preference is an adaptable process during which the organism may change its metabolism in accordance with the environment. The roles of a class of guanylyl cyclases in sensing and behaviors will also be studied as well as possible connections to the classical transcriptional pathways. This type of analysis is only possible with a finely controlled oxygen delivery system. The general techniques developed in this study should impact other C. elegans researches of sensing and behaviors such as odor discrimination and thermo-sensation.