Measuring and Mathematically Modeling Ionic Transport in Auditory Systems

在整个动物王国中，耳朵经过精心调整，可以捕捉空气中的振动，使动物能够远距离感知周围的世界。将纳米大小的运动转化为听觉基础的电事件的感觉受体在脊椎动物和无脊椎动物的耳朵中具有完全不同的形状和位置。尽管如此，值得注意的是，所有听觉受体都依赖于细胞间钾浓度的差异来为其提供动力，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，这些细胞位于其触角内，以了解导致这种钾梯度发展的过程。这项研究的结果将产生测量细胞内外钾浓度的分子工具。此外，该项目还将开发数学工具，以阐明复杂细胞系统的运作，作为更广泛的影响目标的一部分，它还将开发一套实验，使用Backyard Brains的设备，可以在高中生物课上进行，旨在帮助学生了解生物体中的电流流动，这一想法对许多学生来说是一个挑战。暑期讲习班将为高中教师提供使用这些设备的机会，然后这些设备将供他们在教室里使用。此外，该项目还将通过培养本科生和研究生来扩大爱荷华州大学的计算生物学/神经科学领域。该提案的核心是使用果蝇耳朵的机械感受器--果蝇的阿片作为研究建立钾梯度过程的易处理模型。蜈蚣是由感觉神经元和支持细胞组成的细胞集合体。其中一个支持细胞是视丘细胞，这是一种神经胶质样细胞，它包裹着感觉树突，创造出一个充满受体淋巴的空间，其中钾离子浓度很高。该项目将使用果蝇社区开发的强大遗传工具，以确定参与产生钾梯度的离子转运蛋白的性质和位置。该项目建议开发新的基因编码钾指示剂，以确定离子在蛋白石空间中的浓度。此外，将建立数学模型，捕捉耦合的微乳细胞及其细胞外空间的动态，并塑造苍蝇耳朵的电特性。关于细胞间电扩散过程的耦合，有很多东西需要了解，以澄清对细胞系综（如上皮细胞）中几个生理过程的理解。由于蚊子耳朵中也发现了寄生虫，这项研究可以提供新的见解，以帮助打击这种突出的疾病载体。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.