Cytoskeletal functions in cell aging and disease

细胞衰老和疾病中的细胞骨架功能

基本信息

批准号：
10400494
负责人：
KENNETH G CAMPELLONE
金额：
$ 8.37万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10400494
关键词：
Actin-Binding Protein Actins Acute Adaptor Signaling Protein Address Affinity Chromatography Age Aging Air Animal Model Animals Anti-Bacterial Agents Area Attenuated Autoimmune Automobile Driving Autophagocytosis Autophagosome Back Bacteria Bacterial RNA Binding Binding Proteins Biochemistry Biogenesis Bioinformatics Biological Assay Biological Process Biological Sciences Biology Biology of Aging Biophysics Biotechnology Blood Brain Brain Diseases Burn injury Carbon Dioxide Caspase Cell Aging Cell Culture Techniques Cell Shape Cell model Cells Cellular Structures Cellular biology Centers for Disease Control and Prevention (U.S.)Centromere Characteristics Chromatography Citrobacter rodentium Clathrin Clinical Clinical Investigator Collaborations Color Communicable Diseases Communities Complement Complex Computer Models Computer software Computers Confocal Microscopy Connecticut Cryopreservation Cytoskeletal Proteins Cytoskeleton Cytotoxic T-Lymphocytes DNA Data Data Analyses Development Diabetes Mellitus Diagnosis Diarrhea Digestion Disease Disease Outbreaks Disease susceptibility Doctor of Medicine Doctor of Philosophy Documentation Educational process of instructing Elderly Elements Endocytosis Endoplasmic Reticulum Endothelial Cells Environment Equipment Escherichia coli EHEC Escherichia coli Infections Etiology Event Exocytosis Faculty Faculty Workshop Family Fellowship Program Floor Flow Cytometry Fluorescence Freezing Functional disorder Funding Future Galloway syndrome Gastroenterology Gel Gene Expression Profiling Genetic Genetic Diseases Genome Genomic medicine Genomics Geriatrics Gerontology Goals Golgi Apparatus Gram-Negative Bacteria Grant Growth Guanosine Triphosphate Phosphohydrolases Guidelines HDAC6 gene Health Healthcare Hematological Disease Hemorrhagic colitis Herpesviridae Home Homeostasis Homologous Gene Human Human Resources Hybrids Hyperglycemia IACUC Image Analysis Immune Immune System Diseases Immune response Immune system Immunity Immunologics Immunology Incubators Infant Infection Inflammasome Inflammation Inflammation Mediators Inflammatory Infrastructure Inherited Injury Insecta Institutes Interleukin-1 Investigation Investments Joints K-Series Research Career Programs Kidney Kidney Diseases Laboratories Laboratory Study Lasers Leukocytes Licensing Link Longevity Maintenance Malignant Neoplasms Mammalian Cell Manuscripts Measures Mediating Medical center Medical emergency Membrane Methods Microbiology Microfilaments Microscope Microscopy Microtubule Polymerization Microtubules Mission Modeling Mohawk Molecular Molecular Biology Monitor Monomeric GTP-Binding Proteins Motor Mus Muscular Atrophy Mutation Natural Immunity Nature Neurobiology New England Normal Cell Organelles Oryctolagus cuniculus Outcome Pathogenesis Pathway interactions Patients Phagocytes Physicians Physics Physiology Positioning Attribute Postdoctoral Fellow Preparation Printing Process Protein Family Proteins Protocols documentation Quality Control Quality of life Race Recommendation Recording of previous events Recycling Registered nurse Regulation Renal function Renal glomerular disease Research Research Personnel Research Project Grants Resources Role Scanning Science Scientist Series Services Shapes Shiga-Like Toxin II Shipping Shock Signal Transduction Sister Site Skeleton Son Starvation Structure Students Syndrome System Tail Telephone The Jackson Laboratory The Sun Time Tissue Banks Training Travel Ubiquitin Ubiquitination United States United States National Institutes of Health Universities University resources Up-Regulation Vibrio Walkers Walking Wasps Wiskott-Aldrich Syndrome Word Processing Work Yang age related aged analytical ultracentrifugation arm autoinflammatory base biophysical analysis cell age cell motility charge coupled device camera cytokine developmental disease diabetic doctoral student experience experimental study extracellular faculty research fluorescence microscope foodborne illness functional independence genetic analysis genome sequencing glomerular filtration glomerulosclerosis graduate student healthspan host-microbe interactions human disease immune function improved indexing inflammatory disease of the intestine influenza infection innate immune mechanisms innovation insight instrument instrumentation interest kidney cell laptop link protein macrophage medical schools meetings member microbiota mouse model muscle regeneration nephrin neuron development pathogen phosphatidylinositol 3-phosphate podocyte professor programs protein complex protein purification recruit response sample collection soft drink square foot success symposium systemic juvenile idiopathic arthritis trafficking trait trend undergraduate student

项目摘要

7. PROJECT SUMMARY Understanding how human cells organize, shape, and move their membrane-bound organelles is one of the most fundamental problems in biology. To address this challenge, my laboratory studies how the actin and microtubule cytoskeletons control membrane remodeling and organelle dynamics. As cells age, their ability to properly regulate these processes changes. This is especially true for kidney cells and immune cells, as a variety of renal and inflammatory diseases develop with age. However, the differences in cytoskeletal functions that give rise to these cellular changes during the aging process are poorly understood. In human cells, actin filament networks are assembled by proteins called nucleation factors from the Wiskott-Aldrich Syndrome Protein (WASP) family. Despite their importance in remodeling membranes during a wide range of processes, these nucleation factors have not been well characterized, especially as they relate to aging and mechanisms of human disease. I have a long-standing interest in determining how the cytoskeleton drives membrane dynamics in normal cells, and how these functions are altered in the context of infectious and genetic diseases. The immediate goal of this Career Development Award is to allow me to initiate another avenue of investigation on the role of the cytoskeleton in cell aging so that I can achieve my long-term goal of leading a lab which studies cytoskeletal functions in health, aging, and disease. These goals will be achieved by completing four specific aims: (1) Define roles for actin nucleation factors and regulators of autophagy in kidney disease, including Nephrocerebellar Syndrome (NCS); (2) Determine functional links between the cytoskeleton, autophagy, cytokine secretion, and inflammation during infection and aging; (3) Deepen my training in the biology of aging through collaborative training experiences at the Jackson Laboratory's Nathan Shock Center of Excellence in the Basic Biology of Aging and at the Center on Aging at the UConn Health Center; (4) Develop into an independent investigator in the basic biology of cell aging. Given my expertise in cytoskeletal biology, plus my existing grant on the role of actin nucleation in autophagy and disease, my lab is uniquely positioned to provide key mechanistic insights into the relationships among actin nucleation factors, autophagy, kidney function, inflammation, and aging.

7. 项目概要了解人类细胞如何组织、塑造和移动其膜结合细胞器是其中之一生物学中最基本的问题。为了应对这一挑战，我的实验室研究了肌动蛋白和微管细胞骨架控制膜重塑和细胞器动力学。随着细胞老化，它们的能力适当调节这些过程的变化。对于肾细胞和免疫细胞来说尤其如此，因为随着年龄的增长，各种肾脏疾病和炎症疾病也会发生。然而，细胞骨架功能的差异人们对衰老过程中引起这些细胞变化的原因知之甚少。在人体细胞中，肌动蛋白丝状网络由来自 Wiskott-Aldrich 综合征的称为成核因子的蛋白质组装而成蛋白质 (WASP) 家族。尽管它们在各种过程中重塑膜方面发挥着重要作用，这些成核因子尚未得到很好的表征，特别是它们与老化和机制有关人类疾病。我长期以来对确定细胞骨架如何驱动膜有兴趣正常细胞的动力学，以及这些功能在传染病和遗传疾病的背景下如何改变。该职业发展奖的直接目标是让我开启另一条途径研究细胞骨架在细胞衰老中的作用，以便我能够实现领导细胞衰老的长期目标研究健康、衰老和疾病中细胞骨架功能的实验室。这些目标将通过以下方式实现完成四个具体目标：（1）定义肌动蛋白成核因子和自噬调节因子的作用肾脏疾病，包括肾小脑综合症（NCS）； (2) 确定各部门之间的功能联系感染和衰老过程中的细胞骨架、自噬、细胞因子分泌和炎症；（三）深化我的通过杰克逊实验室内森的协作培训经验进行衰老生物学培训休克衰老基础生物学卓越中心和康涅狄格大学健康中心衰老中心中心; （4）培养成为细胞衰老基础生物学的独立研究者。鉴于我的专业知识细胞骨架生物学，加上我现有的关于肌动蛋白成核在自噬和疾病中的作用的资助，我的实验室是具有独特的地位，可以为肌动蛋白成核因子之间的关系提供关键的机制见解，自噬、肾功能、炎症和衰老。