Regulation of Selective Endocytic Transport

智力价值细胞必须吸收营养，与外界环境沟通，并迅速适应环境条件的变化。为了完成这些任务，细胞表面（质膜）的组成不断调整。通过胞吐过程，细胞将新合成的分子传递到质膜或细胞外空间。通过相反的称为内吞作用的过程，细胞内化表面成分。例如，细胞利用内吞作用吸收营养物质，如铁、维生素和嵌入质膜的受体结合的脂质。一旦进入细胞，营养物质就从受体中释放出来，用于各种生物合成过程。在内吞过程中，一部分质膜被拉入细胞内部，形成一个小的球形结构，称为内吞囊泡。各种细胞成分负责：(1)选择哪些受体和其他膜蛋白将被内化；(2)使膜弯曲产生早期的内吞囊泡；(3)提供将囊泡拉入细胞的力。基本的细胞成分被称为衔接蛋白、网格蛋白和肌动蛋白细胞骨架，介导了内吞囊泡形成的三个步骤。本实验室正在研究衔接蛋白、网格蛋白和肌动蛋白细胞骨架进行内吞过程的分子机制。具体而言，本项目侧重于如何在机制上和时间上协调这三个步骤。这些细胞成分及其介导的内吞过程在所有真核细胞中都是保守的，是生命所必需的。这项研究是使用酵母细胞进行的，酵母细胞是一种极好的模型系统，适用于各种实验策略。更广泛的影响该项目将在以下几个方面产生广泛的影响：(i)该项目将有助于增加科学和教育的多样性。该项目将支持：一名少数族裔博士生，一名来自少数族裔群体的杰出女性研究助理教授，以及一名来自少数族裔服务机构的本科生，他们将参加实验室的夏季研究经历（REU计划）。该项目还将支持一位积极参与科罗拉多研究生教育和教授联盟的少数族裔助理教授，该联盟旨在增加少数族裔学生在获得科学、技术、工程和数学（STEM学科）研究生学位方面的历史代表性不足的人数。（ii）进行研究的研究生和本科生将通过撰写报告和手稿、举办部门研讨会和参加科学会议，接受广泛使用的技术、批判性思维和演讲技巧的培训。（三）本项目的本科生和研究生将参与将内吞作用研究和荧光显微镜带入中学课堂。这项外展活动是在一个英语/西班牙语双语的中学项目中发起的，有许多少数民族儿童参加。学生们将用荧光显微镜观察细胞的不同部分，并进行实验，旨在教授他们基本的细胞生物学概念，激发他们对科学的兴趣。这个项目的成果将在科学期刊上发表，并在专门会议和国家细胞生物学会议上提出，从而影响更广泛的科学界。

Intellectual Merit Cells must take up nutrients, communicate with the external environment, and quickly adapt to changes in environmental conditions. To carry out these tasks, the composition of the cell surface (the plasma membrane) is continually adjusted. Through the process of exocytosis, the cell delivers newly synthesized molecules to the plasma membrane or the extracellular space. By the opposite process called endocytosis cells internalize surface components. For example, cells utilize endocytosis to take up nutrients, such as iron, vitamins, and lipids bound by receptors embedded in the plasma membrane. Once inside the cell, the nutrients are released from the receptors and used in various biosynthetic processes. During endocytosis, a portion of the plasma membrane is pulled into the inside of the cell forming a small, spherical structure known as an endocytic vesicle. Various cellular components are in charge of: (1) selecting which receptors and other membrane proteins will be internalized; (2) bending the membrane to generate the incipient endocytic vesicle; and (3) providing the force to pull the vesicle into the cell. Fundamental cellular components known as adaptor proteins, clathrin, and the actin cytoskeleton mediate the three steps of endocytic vesicle formation. This laboratory is studying the molecular mechanisms by which adaptor proteins, clathrin and the actin cytoskeleton carry out the endocytic process. Specifically, this project focuses on how the three steps are mechanistically and temporally coordinated. These cellular components and the endocytic process they mediate are conserved in all eukaryotic cells and are essential for life. The research is carried out using yeast cells, a superb model system amenable to a wide range of experimental strategies. Broader Impacts The project will have broad impacts in several ways: (i) This project will contribute to increase diversity in science and education. This project will support: an under-represented minority PhD student, an outstanding female Research Assistant Professor from an under-represented group, and undergraduate students from a largely minority serving institution who will participate in summer research experiences (REU program) in the laboratory. The project will also support a minority Assistant Professor actively involved in the Colorado Alliance for Graduate Education and the Professoriate, a program seeking to increase the number of minority students historically under-represented in obtaining graduate degrees in Science, Technology, Engineering, and Mathematics (STEM disciplines). (ii) The graduate and undergraduate students who conduct the studies will be trained in widely used techniques, critical thinking, and presentation skills through writing reports and manuscripts, giving departmental seminars, and attending scientific conferences.(iii) Both undergraduate and graduate students in this project will be involved in taking endocytosis studies and fluorescence microscopy into middle school classrooms. This outreach activity is initiated in a bilingual English/Spanish middle school program attended by numerous under-represented minority children. The students will observe different parts of the cell with a fluorescence microscope and perform experiments designed to teach them basic cell biology concepts and spark their interest in science.(iv) Results from this project will be published in scientific journals, and presented at both specialized conferences and national cell biology meetings, thus impacting the broader scientific community.