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Replacement of Widefield Imaging System

更换宽场成像系统

基本信息

批准号：
10388921
负责人：
Valentin Boerner
金额：
$ 24.9万
依托单位：
CLEVELAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-22 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10388921
关键词：
26S proteasome Aging Alleles Aneuploidy Animal Model Appearance Biochemical Birth Caenorhabditis elegans Cell Nucleus Chromosome Arm Chromosome Pairing Chromosome Segregation Chromosome Structures Chromosomes Clinical Collaborations Complex Congenital Abnormality Cytology Cytoplasm Data Defect Enhancers Ensure Eukaryota Event Exhibits Funding Future Genetic Genetic Recombination Germ Cells Global Change Goals Homologous Gene Human Impairment Infertility Intervention Investigation Link Mediating Medical Meiosis Meiotic Recombination Microscope Microscopy Modeling Morphogenesis Morphology Mus Mutation Organism Pathway interactions Peptide Hydrolases Pharmacology Polyubiquitination Pregnancy Process Proteasome Inhibition Proteasome Inhibitor Proteins Proteolysis Proteomics Reproductive Health Research Resolution Role Saccharomycetales Science Series Site Sterility Sumoylation Pathway Suppressor Mutations System Time Ubiquitination United States National Institutes of Health Work cancer therapy chromosome missegregation genetic regulatory protein homologous recombination imaging system insight live cell imaging misfolded protein multicatalytic endopeptidase complex mutant novel parent grant programs protein degradation public health relevance recruit reproductive success segregation success transmission process

项目摘要

PROJECT SUMMARY The central aim of the parent grant is to identify roles of the proteasome along meiotic chromosomes. The 26S proteasome is the main site of protein degradation in all eukaryotes. It is a compartmentalized, multicomponent protease that resides both in the cytoplasm and the nucleus. Cytoplasmic proteasome functions in eliminating regulatory and misfolded proteins have been recognized for a long time. Functions of the proteasome in the nucleus are much less understood. We recently discovered that during meiosis I, the 26S proteasome is recruited in an evolutionarily conserved manner to chromosomes where it controls homolog pairing, synapsis and recombination. Using a combination of high-resolution microscopy, genetic and proteomic approaches, we are pursuing three aims that build on this discovery: First, we are using tightly controlled conditional alleles to systematically characterize roles during meiosis of different proteasome components. Second, we are identifying substrates of the proteasome relevant to chromosome pairing and recombination, providing insights into a class of molecules that need to be degraded to ensure normal meiotic progression. Third, we are identifying determinants for proteasome recruitment to chromosomes. Meiotic chromosome segregation defects in absence of a functional proteasome emphasize the importance for reproductive health of a better understanding of chromosome- associated proteolysis. Our analysis is also relevant to cancer therapy where proteasome inhibitors have become increasingly important. Many of our approaches involve high resolution and live-cell imaging in the model eukaryote budding yeast. In this supplement proposal, we are requesting funds for an advanced high-resolution, live imaging system as replacement for our aging current microscope. Our current system has given us valuable insights but has become unreliable and is near the end of its lifetime. A state-of-the- art imaging system will enable us to maintain and further enhance a high impact research program into mechanisms of chromosome transmission.

项目总结