Membrane Regulation of Cell Permeability and Protein Function

细胞通透性和蛋白质功能的膜调节

• 批准号: 1052477
• 负责人: Toby Allen
• 金额: $ 48万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1052477&HistoricalAwards=false
• 关键词: Membrane; Regulation; Cell; Permeability; Protein

Intellectual MeritBiological membranes mediate biological activity by providing an interface for cell-surface recognition, signaling, and transport. One cannot understand cellular function without understanding membranes. They are both the gateways into cells and home to a range of proteins with critical functions (pumps, channels, carriers, receptors, enzymes and energy transducers). Prof. Allen is developing rigorous computational approaches, in concert with experiments, to describe the physical rules underlying biological membrane permeability and membrane protein activity. His laboratory is unveiling the mechanisms of membrane deformations and permeation by ions, charged peptides and ionophores for improved understanding of the actions of viral, toxin and antimicrobial peptides, as well as for the development of novel drug delivery and bio-sensing applications. Prof. Allen has also devised a realizable strategy, employing peptides as model trans-membrane protein segments, to calculate the effects of lipid composition and pharmacological agents on protein activation, and is exploring the regulation of ion channel proteins, crucial to our nervous systems. Broader ImpactsThis project is providing molecular-level understanding for critical biological functions that will assist in future pharmacological and biotechnological innovations. The quantitative descriptions of protein-membrane interactions emerging from this research are needed to understand the distribution, folding and function of membrane-proteins, which make up nearly a third of the human genome and two thirds of all drug targets, as well as the actions of viruses, toxins, antimicrobial agents and nanodevices for drug delivery and to probe cells at the molecular level. Prof. Allen is actively seeking new and exciting ways of harnessing the curiosity and enthusiasm of young and underprivileged students. He is introducing biomolecular simulation into the undergraduate and graduate curriculum, setting up an educational framework for future generations. He is creating his own initiatives, including the training event SYLICCO (SYmposium on Learning and Industry targeting Computational Chemistry Opportunities), for students to learn the skills of computational chemistry and biophysics and lead them to careers in academia and industry. He is providing opportunities for students from disadvantaged backgrounds, including the development of, and participation in regional outreach and high school programs (e.g. COSMOS, Young Scholars, ACS Seed and Explorit). Prof. Allen is committed to enhancing the UC Davis environment for outreach education, taking this NSF funded science to the grass roots of the community to provide students with exciting opportunities in biomolecular science.This project is funded jointly by the Cellular Process Cluster and the Biomolecular Dynamics, Structure, and Function cluster.

生物膜通过提供细胞表面识别、信号传递和运输的接口来调节生物活性。不了解细胞膜就不能了解细胞的功能。它们既是进入细胞的门户，也是一系列具有关键功能的蛋白质（泵、通道、载体、受体、酶和能量传感器）的家园。艾伦教授正在开发严格的计算方法，与实验相一致，以描述生物膜渗透性和膜蛋白活性的物理规则。他的实验室正在揭示膜变形和离子、带电肽和离子载体渗透的机制，以提高对病毒、毒素和抗菌肽的作用的理解，以及对新型药物输送和生物传感应用的开发。Allen教授还设计了一个可实现的策略，利用多肽作为模型跨膜蛋白片段，计算脂质组成和药物对蛋白质激活的影响，并正在探索对神经系统至关重要的离子通道蛋白的调节。更广泛的影响该项目为关键的生物学功能提供分子水平的理解，这将有助于未来的药理学和生物技术创新。从这项研究中出现的蛋白质-膜相互作用的定量描述需要理解膜蛋白的分布、折叠和功能，膜蛋白构成了人类基因组的近三分之一和所有药物靶点的三分之二，以及病毒、毒素、抗菌剂和纳米装置的作用，用于药物传递和在分子水平上探测细胞。艾伦教授正在积极寻求新的和令人兴奋的方法来利用年轻和贫困学生的好奇心和热情。他正在将生物分子模拟引入本科和研究生课程，为后代建立一个教育框架。他正在创建自己的计划，包括培训活动SYLICCO（以计算化学机会为目标的学习和行业研讨会），让学生学习计算化学和生物物理学的技能，并引导他们进入学术界和工业界的职业生涯。他为来自弱势背景的学生提供机会，包括发展和参与区域外展和高中项目（例如COSMOS， Young Scholars， ACS Seed和Explorit）。Allen教授致力于改善加州大学戴维斯分校的外展教育环境，将这项由美国国家科学基金会资助的科学带到社区的基层，为学生提供令人兴奋的生物分子科学机会。该项目由细胞过程集群和生物分子动力学、结构和功能集群共同资助。