TriMED: Measuring, Modeling and Manipulating Excitability and Disease

项目总结 神经系统是一个电子系统，神经元是典型的电活动细胞，但离子 运输是调节身体中每个细胞的基础，无论是否兴奋，几乎20% 被批准的药物实际上对离子通道起作用。多种神经系统疾病，包括运动 疾病，偏头痛和癫痫，显然可以由特定离子的遗传突变直接引起。 通道和转运体，但离子转运缺陷也与所有大的疾病有关，从癌症 从心脏病到阿尔茨海默氏症。我们的目标是产生一批研究人员，他们在- 深入了解膜生物学，结合最先进的技术技能，进行 兴奋性的基础研究和翻译研究。预期的结果是研究人员有能力 利用(I)膜的蓬勃发展改变兴奋性研究--从而改变治疗方法 蛋白质结构测定，(Ii)通过电生理学和成像测量兴奋性，从 分子到组织水平，(Iii)生物和计算的建模，以及(Iv)兴奋性的调节， 无论是药理上的还是生理上的。该计划将支持后期博士后和博士后 双导师研究的受训者，有来自上述基本重点领域之一的主要导师， 另一位导师可能来自应用重点领域--包括方法开发或 生物体和临床研究。除了密集的研究经验，学员还将参加一个 教学课程，旨在加深对研究的理解，以及致力于培训 助学金写作、演讲和职业发展。该计划的教职员工导师是根据以下方面选择的 背景和职业阶段的广度和多样性，都有良好的资金和职业记录 对受训人员发展、培训机会的跨学科性质和体制的承诺 承诺结合在一起，培育了一个适合这一削减后的计划目标的独特环境。这个 该计划将确定具有适当背景、致力于兴奋性职业生涯的个人 研究，并为他们提供指导的博士后和博士后研究经验，将建立 为未来的职业生涯奠定基础，能够为神经科学和疾病带来新的见解和工具 兴奋的感觉。

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.