Cellular logic of phenotype

表型的细胞逻辑

• 批准号: 8139017
• 负责人: JAMES H EBERWINE
• 金额: $ 77.96万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8139017
• 关键词: Cell Differentiation process; Cell Polarity; Cell Survival; Cells; Coupled; Data; Destinations; Diffuse; Gene Expression Profile; Genetic Transcription; Genomics; Goals; Laboratories; Lasers; Light; Logic; Memory; Phenotype; Population; Procedures; Proteins; RNA; Relative (related person); Technology; Therapeutic; cell type; insight; novel; theories

The Cellular Logic of Phenotype The goal of this application is to develop a strategy for predictably and reproducibly altering the phenotype of primary cells in culture. Differentiated cell types differ from each other in their RNA profiles (relative as well as absolute abundances of the RNAs they express). I hypothesize that, by the transferring entire RNA profiles from donor to recipient cells in a way that makes the recipient cells' survival dependent on donor RNA, the donor RNA will change the recipient into a destination phenotype that mimics the donor cell phenotype. This procedure is called Transcriptome Induced Phenotype Remodeling (TIPeR). Having the ability to transfer cell phenotypes between cells would provide important new insights into mechanisms controlling cell differentiation. The theory and technical strategies to accomplish this are being developed in my laboratory. Specifically, using laser light induced phototransfection (developed in my lab), we transiently produce pores in the host primary cell, through which RNA populations (in which RNA species and abundances are carefully controlled), can diffuse. Preliminary data shows that donor cell RNA populations carry "memory functions" in that, donor RNA can induce long-term changes in genomic transcription of the host cells thereby changing the functional phenotype of the host cells to that of the destination phenotype. This is due in part to the activity and abundances of the specific proteins made from the host cell RNA mixture. Through developing various high- throughput quantitative "Omics" level phenotyping technologies coupled with the TIPeR procedure it is anticipated that the "genomics logic" of phenotype will be discerned. An understanding of this logic will permit the creation of specific cell types at will. The ability to selectively and rationally create cellular phenotypes promises to provide important insights into the fundamental mechanisms underlying cellular polarity, functioning and phenotype stability and may yield novel "individualized medicinal therapeutics".

表型的细胞逻辑

项目成果

Towards A Fully Automated High-Throughput Phototransfection System.

• DOI: 10.1016/j.jala.2010.03.003
• 发表时间: 2010-08-01
• 期刊: JALA
• 作者: Cappelleri, David J.;Halasz, Adam;Sul, Jai-Yoon;Kim, Tae Kyung;Eberwine, James;Kumar, Vijay
• 通讯作者: Kumar, Vijay