PROGRAM PROJECT: RED CELL MEMBRANE STUDIES

项目项目：红细胞膜研究

• 批准号: 8144301
• 负责人: Mohandas Narla
• 金额: $ 162.62万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-30 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8144301
• 关键词: Affect; Anemia; Biochemistry; Biological; Biophysics; Bone Marrow; Cell Differentiation process; Cell membrane; Cellular biology; Cytoskeletal Proteins; Cytoskeleton; Erythrocytes; Erythroid Cells; Erythropoiesis; Family; Functional disorder; Genetic; Goals; Health; Hematology; Hematopoiesis; Hematopoietic; Homeostasis; Individual; Molecular; Molecular Biology; Parasites; Parasitology; Physiology; Proteins; Research; Research Personnel; Role; Somatic Cell; Structure-Activity Relationship; base; erythroid differentiation; human disease; improved; insight; interest; membrane assembly; membrane biogenesis; membrane skeleton; programs; skeletal

DESCRIPTION (provided by applicant): The overall objectives of this program are to develop a detailed understanding of the molecular and structural basis for the genesis and assembly of the red cell, with emphasis on the membrane skeleton; and to develop an improved mechanistic understanding of erythropoiesis, with the goal of defining pathophysiologic mechanisms of anemia, a major health problem affecting over billion individuals around the world. The scope of the proposed research program also includes delineating the role of cytoskeleton in regulating hematopoietic cell differentiation. To achieve these broad goals, four complementary approaches are proposed: 1) Develop a detailed understanding of the molecular and structural basis for the functions of an important family of cytoskeletal proteins in erythroid cells; 2) Obtain detailed mechanistic understanding of the functional and biological consequences of interaction between proteins of the malarial parasite and the red cell; 3) Delineate mechanisms involved in enucleation and membrane biogenesis during terminal erythroid differentiation; and 4) Obtain mechanistic understanding of the role of the bone marrow matrix stiffness on hematopoiesis, with particular emphasis on erythropoiesis. To achieve these objectives, a group of investigators with expertise in hematology, biochemistry, cell biology, biophysics, genetics, parasitology, and molecular biology, as well as a long standing interest in red cell membrane physiology, have come together to mount a concerted effort. It is anticipated that information garnered during these studies will contribute towards increased insights into the role of skeletal proteins in membrane assembly, homeostasis and structure-function relationships in erythroid cells in particular, and somatic cells in general, that will have significant impact on our understanding of the pathophysiology of important human diseases.

描述（由申请人提供）： 该计划的总体目标是详细了解红细胞的发生和组装的分子和结构基础，重点是膜骨架;并提高对红细胞生成的机制理解，以定义贫血的病理生理机制为目标，贫血是影响全球数十亿人的主要健康问题。拟议的研究计划的范围还包括划定在调节造血细胞分化的细胞骨架的作用。为了实现这些广泛的目标，提出了四个互补的方法：1）发展一个重要的细胞骨架蛋白家族在红系细胞中的功能的分子和结构基础的详细理解：2）获得详细的机制的理解疟原虫和红细胞的蛋白质之间的相互作用的功能和生物学后果; 3）描述终末红细胞分化过程中涉及去核和膜生物发生的机制;和4）获得骨髓基质硬度对造血作用的机制理解，特别强调红细胞生成。为了实现这些目标，一组具有血液学，生物化学，细胞生物学，生物物理学，遗传学，寄生虫学和分子生物学专业知识的研究人员，以及对红细胞膜生理学的长期兴趣，已经走到一起，共同努力。预计在这些研究过程中获得的信息将有助于增加对骨骼蛋白在膜组装，稳态和结构-功能关系中的作用的了解，特别是在红系细胞和体细胞中，这将对我们理解重要的人类疾病的病理生理学产生重大影响。