Cellular logic of phenotype

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications & trials

Abstract

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