TriMED: Measuring, Modeling and Manipulating Excitability and Disease

项目摘要 神经系统是一个电系统，神经元是典型的电活性细胞，但离子 运输是调节体内每个细胞的基础，无论是否兴奋，几乎20% 对离子通道有效的药物。多种神经系统疾病，包括运动 偏头痛和癫痫，显然可以直接由特定离子的遗传突变引起。 离子通道和转运蛋白，但有缺陷的离子转运也与每一种重大疾病有关， 到心脏病到老年痴呆症。我们的目标是培养一批具有适当知识的研究人员- 深入了解膜生物学，结合最先进的技术技能，开展 兴奋性的基础和转化研究。预期的结果是研究人员有能力 通过利用（i）膜的迅速发展， 蛋白质结构测定，（ii）兴奋性的测量，通过电生理学和成像，从 分子到组织水平，（iii）建模，生物学和计算的，以及（iv）兴奋性的调节， 不管是肉体上还是精神上该计划将支持后期的博士前和博士后 双导师研究的学员，主要导师来自上述基本重点领域之一， 第二位导师可能来自应用重点领域-包括方法开发或 生物学和临床研究。除了密集的研究经验，学员将参加一个 教学课程，旨在深入了解研究，以及专门培训活动， 资助写作、演讲和职业发展。该计划的教师导师，选择方面， 背景和职业阶段的广度和多样性，所有这些都具有良好的资金和 对受训者发展的承诺，培训机会的跨学科性质， 承诺联合收割机，以促进一个独特的环境，适合这个TriMED计划的目标。的 该计划将确定具有适当背景的个人，他们致力于兴奋性的职业生涯 研究，并为他们提供指导前和博士后研究经验，将建立一个 未来职业的基础，能够带来新的见解和工具，以承担神经科学和疾病 兴奋性。

PROJECT SUMMARY The nervous system is an electrical system, and neurons are the archetypal electrically active cell, but ion transport is fundamental to the regulation of every cell in the body, whether excitable or not, and almost 20% of approved drugs actually work on ion channels. Multiple neurological diseases, including movement disorders, migraine, and epilepsy, can clearly be caused directly by inherited mutations of specific ion channels and transporters, but defective ion transport is also associated with every big disease, from cancers to heart disease to Alzheimer's disease. We aim to generate a cohort of researchers with the appropriate in- depth understanding of membrane biology, in combination with state-of-the-art technical skills, to carry out basic and translational research in excitability. The intended result is researchers with the capability to transform excitability research – and hence therapies – by harnessing burgeoning advances in (i) membrane protein structure determination, (ii) measurement of excitability, by electrophysiology and imaging, from molecular to tissue levels, (iii) modeling, both biological and computational and (iv) modulation of excitability, both pharmacologically and physically. The program will support later stage pre-doctoral and post-doctoral trainees in dual-mentored research, with a primary mentor from one of the above fundamental focus areas, and a second mentor who could be from an applied focus area – including methods development or organismal and clinical studies. In addition to intensive research experiences, trainees will participate in a didactic course, geared towards in-depth research understanding, as well as activities devoted to training in grant writing, presentations, and career development. The program faculty mentors, chosen with regard to breadth and diversity of background and career stage, all with strong track records of funding and commitment to trainee development, the interdisciplinary nature of training opportunities, and institutional commitments combine to foster a unique environment suited to the goal of this TriMED program. The program will identify individuals with appropriate backgrounds, who are committed to a career in excitability research, and provide them with mentored pre- and post-doctoral research experiences that will establish a foundation for future careers capable of bringing new insights and tools to bear in neuroscience and disorders of excitability.