Role for ion conducting proteins in cortical malformation diseases

离子传导蛋白在皮质畸形疾病中的作用

• 批准号: 10435714
• 负责人: Richard S Smith
• 金额: $ 9.21万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-22 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10435714
• 关键词: Area; Biological Assay; Brain; Brain Diseases; Cell physiology; Cerebral Palsy; Cerebral cortex; Cerebrum; Cortical Malformation; Development; Diagnosis; Disease; Epilepsy; Functional disorder; Gene Mutation; Goals; Health; Human; Individual; Ion Channel; Ions; Nature; Organoids; Physiological; Plant Roots; Proteins; Research; Role; Speech; Testing; Work; disease phenotype; genetic testing; improved; innovation; malformation; mouse model; newborn neuron; novel; pressure; stem cells

K99 Admin Supplement Project Summary The idea that ion channels can disrupt cortex formation is a new area of study, particularly when exploring the mechanisms activated at a cellular level. Since dividing progenitor cells and newborn neurons in the developing cerebral cortex rely on ions for controlling cellular processes, I will test the new hypothesis that disrupted activity of specific ion fluxes is critical to cortex assembly. Proof of the existence of developmental channelopathies in the brain has remained elusive due to the heterogenous nature of cortical malformations and the fact that they are often are under extreme negative pressure evolutionarily. Given that I am describing and categorizing brain disorders that improve our understanding of disease mechanisms and the treatment of conditions related to malformation of cortical development (MCD), the significance of this work to human research will immediately improve health is immediate as the results generated by this genetic testing for diagnosed disorders. I will complete this research with a combination of both proven and innovative strategies, including: Aim 1) Completed (K99 Aim 1, year 1) Aim 2) Characterizing a novel mouse model for a developmental channelopathy; Aim 3) Development of a novel physiological assay in developing human cerebral organoids.

K99管理员补充项目摘要 离子通道可能破坏皮层形成的想法是一个新的研究领域，尤其是 探索在细胞水平激活的机制时。由于将祖细胞分开 发育中的大脑皮层中的新生神经元依赖于控制细胞 过程，我将测试一个新的假设，即特定离子通量的破坏活动是至关重要的 到皮质组件。大脑中发育通道病存在的证明 由于皮质畸形的异质性质以及事实，仍然难以捉摸 它们通常在进化上处于极端负压下。鉴于我正在描述 并对脑部疾病进行分类，以提高我们对疾病机制的理解和 治疗与皮质发育畸形（MCD）有关的条件， 这项工作对人类的意义 研究将立即改善 健康是直接的，因为结果产生了 诊断性疾病的基因测试。我会完成这个 与经过验证和创新策略结合的研究，包括： 目标1）完成（K99 AIM 1，1年） 目标2）表征开发通道病的新型小鼠模型； 目的3）开发一种新型生理测定法，以开发人类脑器官。