Genome-Wide Growth Factor Discovery in the CNS

中枢神经系统全基因组生长因子的发现

• 批准号: 6793539
• 负责人: JOHN J HARRINGTON
• 金额: $ 34.9万
• 依托单位: ATHERSYS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6793539
• 关键词: biotechnology; cell differentiation; cell type; central nervous system; functional /structural genomics; gene expression; genetic library; genetic mapping; genetic screening; genetic techniques; green fluorescent proteins; growth factor; high throughput technology; laboratory rat; mitogens; molecular cloning; nerve growth factors; neurotrophic factors; polymerase chain reaction; protein structure function; proteomics; stem cells

DESCRIPTION (provided by applicant): We propose to carry out a rapid genome-wide search for new mitogens and survival factors for stem and precursor cells of CNS, potentially doubling or more the number of known CNS mitogenic and survival factors over the course of two years. To do this, a novel protein expression technology, called Random Activation of Gene Expression (RAGE), will be used. RAGE libraries produced using genomic libraries carried in bacterial artificial chromosomes offer a number of advantages over conventional expression methodologies, including high-level expression without the need for full-length cDNAs. RAGE libraries produced in BAC libraries should allow the majority of secreted factors to be expressed and interrogated in the proposed research program. In addition to potential direct medical and therapeutic benefits, the discovery of new proteins with activities in promoting cell survival and division has considerable benefits on biological research in general. Even the limited number of growth factors available has provided a central foundation for the nascent field of stem cell biology in the CNS. Identifying proteins that further enable regulation of these populations will provide tools that may greatly extend our ability to achieve such important goals as repair of CNS damage.

描述（由申请人提供）：我们建议对中枢神经系统干细胞和前体细胞的新有丝分裂原和存活因子进行快速全基因组搜索，可能在两个过程中使已知中枢神经系统有丝分裂和存活因子的数量增加一倍或更多年。为此，将使用一种称为基因表达随机激活（RAGE）的新型蛋白质表达技术。使用细菌人工染色体携带的基因组文库产生的 RAGE 文库与传统表达方法相比具有许多优势，包括不需要全长 cDNA 的高水平表达。 BAC 文库中产生的 RAGE 文库应允许大多数分泌因子在拟议的研究计划中表达和询问。除了潜在的直接医学和治疗益处外，具有促进细胞存活和分裂活性的新蛋白质的发现对一般生物学研究具有相当大的好处。即使可用的生长因子数量有限，也为中枢神经系统干细胞生物学的新兴领域提供了核心基础。鉴定能够进一步调节这些群体的蛋白质将提供工具，可以极大地扩展我们实现修复中枢神经系统损伤等重要目标的能力。