Measuring and Mathematically Modeling Ionic Transport in Auditory Systems

在整个动物王国里，耳朵能够很好地感知空气中的振动，这使得动物能够在远处感知周围的世界。在脊椎动物和无脊椎动物的耳朵里，把纳米大小的运动转化为听觉基础的电子事件的感觉受体，有着完全不同的形状和位置。尽管如此，值得注意的是，所有的听觉受体都依赖于细胞间钾浓度的差异来提供能量，而不像其他受体使用钠或钙梯度。该项目将使用果蝇（Drosophila melanogaster）“耳朵”中的感觉细胞（位于其触角内）来了解导致这种钾梯度发展的过程。这项研究的结果将产生用于测量细胞内外钾浓度的分子工具。此外，该项目将开发数学工具来阐明复杂细胞系统的运作，并且，作为更广泛影响目标的一部分，它还将开发一套使用后院大脑设备的实验，这些实验可以在高中生物课上进行，旨在帮助学生理解生物体内的电流流动，这对许多学生来说是一个挑战。夏季讲习班将为高中教师提供使用这些设备的机会，然后这些设备将提供给他们在教室中使用。此外，该项目将通过培养本科生和研究生来扩大爱荷华大学的计算生物学/神经科学领域。这一建议的核心是使用果蝇耳朵的机械感受器——翅果，作为研究钾梯度建立过程的一个可处理的模型。脊柱是由感觉神经元和支持细胞组成的细胞群。一种支持细胞是侧肋细胞，它是一种胶质样细胞，包裹着感觉树突，形成一个充满受体淋巴的空间，其中含有高浓度的钾。该项目将使用由果蝇社区开发的强大的遗传工具，来确定参与产生钾梯度的离子转运体的性质和位置。该项目拟开发新的基因编码钾指示剂，以确定柱头空间中的离子浓度。此外，还将建立数学模型，捕捉耦合的翅翼细胞及其细胞外空间的动力学，并塑造苍蝇耳朵的电学特性。关于细胞间电扩散过程的耦合还有很多需要了解的，以澄清对细胞群（如上皮）中几种生理过程的理解。由于蚊子耳朵中也发现了脊柱侧裂，因此这项研究可以为帮助对抗这种主要的疾病媒介提供新的见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Throughout the animal kingdom, ears finely tuned for picking up vibrations in the air allow animals to sense the world around them at a distance. The sensory receptors that translate nanometer-sized movements into electrical events that underlie hearing, have quite different shapes and locations in the ears of vertebrates and invertebrates. Despite this, it is remarkable that all auditory receptors rely on differences in potassium concentrations between cellular compartments to power them, unlike other receptors that use sodium or calcium gradients. This project will use sensory cells in fly (Drosophila melanogaster) 'ears', which are located within its antennae, to understand the processes that lead to the development of such potassium gradients. Results from this research will generate molecular tools for measuring potassium concentrations inside and outside cells. In addition, the project will develop mathematical tools for illuminating the operation of complex cellular systems, and, as part of the broader impact objectives, it will also develop a set of experiments using equipment from Backyard Brains, which can be performed in high school biology classes and which will be designed to help students understand electrical current flow in living organisms, an idea which presents a challenge for many students. Summer workshops will give high school teachers the opportunity to use the equipment, which will then be made available for them to use in their classrooms. In addition, the project will expand the field of Computational Biology/Neuroscience at the University of Iowa by training undergraduate and graduate students.Central to this proposal is the use of scolopidia, the mechanoreceptors of Drosophila ears, as a tractable model for studying the processes that establish potassium gradients. Scolopidia are cellular ensembles, consisting of sensory neurons and supporting cells. One support cell is the scolopale cell, a glial-like cell that envelops the sensory dendrites, creating a space filled with receptor lymph, which has a high potassium concentration. The project will use the powerful genetic tools developed by the Drosophila community, to identify the nature and location of ion transporters involved in generating potassium gradients. The project proposes to develop novel genetically-encoded potassium indicators to determine the ion’s concentration in the scolopale space. In addition, mathematical models that capture the dynamics of the coupled scolopale cell and its extracellular space, and that shape the electrical properties of fly ears, will be built. There is much to learn about the coupling of electrodiffusion processes between cells, to clarify the understanding of several physiological processes in cellular ensembles like epithelia. Since scolopidia are also found in mosquito ears, the research could provide new insights to help combat this prominent disease vector.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.