TriMED: Measuring, Modeling and Manipulating Excitability and Disease

TriMED：测量、建模和操纵兴奋性和疾病

• 批准号: 10627404
• 负责人: Baron Chanda
• 金额: $ 15.76万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-05 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627404
• 关键词: Disease; Measures; Modeling

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.

项目概要 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 运输对于体内每个细胞的调节至关重要，无论是否兴奋，几乎 20% 的批准药物实际上对离子通道有效，包括运动在内的多种神经系统疾病。 偏头痛和癫痫等疾病显然是由特定离子的遗传突变直接引起的 通道和转运蛋白，但离子转运缺陷也与癌症等各种重大疾病有关 我们的目标是培养一批具有适当研究能力的研究人员。 对膜生物学的深入理解，结合最先进的技术技能，开展 兴奋性的基础和转化研究的预期结果是研究人员有能力 通过利用 (i) 膜方面的新兴进展来改变兴奋性研究以及治疗方法 蛋白质结构测定，(ii) 通过电生理学和成像测量兴奋性，来自 分子到组织水平，(iii) 生物和计算建模，以及 (iv) 兴奋性调节， 该计划将为后期博士前和博士后提供支持。 双重指导研究的受训者，其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 除了深入的研究经验外，学员还将参加一系列的活动。 教学课程，旨在深入了解研究，以及致力于培训的活动 该项目的教师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，都具有良好的资金和记录记录 对学员发展的承诺、培训机会的跨学科性质以及制度 这些承诺共同营造了一个适合 TriMED 计划目标的独特环境。 计划将识别具有适当背景、致力于兴奋性职业的个人 研究，并为他们提供指导的博士前和博士后研究经验，这将建立 为未来职业奠定基础，能够为神经科学和疾病带来新的见解和工具 的兴奋。