RUI: Genetic Control of Sensory Hair Cell Membrane Channels in Zebrafish

该奖项由2009年美国复苏和再投资法案(公共法律111-5)资助。脊椎动物耳朵中的感觉神经元--称为毛细胞--探测来自环境的声音、重力和振动刺激，并将其转化为电信号。他们通过在突触释放化学神经递质，将这些信息传递给大脑中的高级神经元。这个项目的长期目标是了解基因组如何指定控制听觉和前庭结构中毛细胞释放神经递质的指令。目前的项目包括利用电生理学方法研究斑马鱼分离的野生型和突变型毛细胞，以表征介导递质释放的膜通道和受体。这种动物模型的使用是适当的，因为它提供了一种简单、可获得的准备，将揭示脊椎动物听力和平衡的遗传和生理控制。将继续进行几个方面的研究。首先，由于钙和钾离子在触发神经递质释放的电和化学事件中的重要性，我们将描述调节这些离子通过毛细胞膜的通道。下一步，由于毛细胞释放的递质可以被其他细胞释放的因子调节，这些因素的受体的存在将被记录下来，并解释受体激活的影响。最后，将分析影响听力和平衡的听觉和前庭突变导致的毛细胞通道和受体特性的变化。希望通过对该模型系统中野生型和突变型动物的研究，更清楚地了解感觉毛细胞在脊椎动物中调节听力和平衡的作用。更广泛的影响：脊椎动物的听力和平衡依赖于内耳感觉毛细胞的电活动。目前的项目旨在发现基因组在控制这些细胞的活动中所起的作用。这项研究将提供一个非常适合于遗传操作和分析的模式物种中毛细胞生物物理性质的亟需调查。该项目的一个主要目标是培养女科学家。圣玛丽山学院的本科生都是女性，其中近75%的人是家里第一个上大学的。此外，超过一半的人来自代表性不足的少数民族。该项目将提供一个指导环境，培训和教育这些妇女进行高质量的独立研究。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Sensory neurons in the ears of vertebrates--called hair cells--detect and transduce sound, gravitational and vibrational stimuli from the environment into electrical signals. They pass on this information to higher order neurons in the brain by releasing chemical neurotransmitters at synapses. The long-term goal of this project is to understand how the genome specifies the instructions that control the release of neurotransmitters from hair cells in auditory and vestibular structures. The present project involves studying isolated wild type and mutant hair cells from zebrafish using electrophysiological methods to characterize the membrane channels and receptors that mediate transmitter release. The use of this animal model is appropriate as it provides a simple, accessible preparation that will shed light on the genetic and physiological control of hearing and balance in vertebrates. Several lines of research will be pursued. First, because of the importance of calcium and potassium ions in the electrical and chemical events triggering neurotransmitter release, the channels that regulate the flux of these ions across hair cell membranes will be characterized. Next, as transmitter release from hair cells can be modulated by factors released by other cells, the presence of receptors for these agents will be documented and the effects of receptor activation explained. Finally, the changes in the properties of hair cell channels and receptors that result from auditory and vestibular mutants that affect hearing and balance will be analyzed. It is hoped that through the study of both wild type and mutant animals in this model system, a clearer understanding of the roles sensory hair cells play in mediating hearing and balance in vertebrates will emerge.Broader Impacts: Hearing and balance in vertebrates are reliant on the electrical activity of sensory hair cells in the inner ear. The present project is designed to discover the role the genome plays in controlling the activity of these cells. This research will provide a much needed investigation of the biophysical properties of hair cells in a model species that is ideally suited to genetic manipulation and analysis. A major goal of the project is to train women scientists. Mount St. Mary's College undergraduates are all women nearly 75% of whom are the first in their families to attend college. Furthermore, more than half are from underrepresented minorities. This project will provide a mentoring environment to train and educate these women in performing high quality independent research.