RESUMO
The large-scale generation and integration of genomic, proteomic, signalling and metabolomic data are increasingly allowing the construction of complex networks that provide a new framework for understanding the molecular basis of physiological or pathophysiological states. Network-based drug discovery aims to harness this knowledge to investigate and understand the impact of interventions, such as candidate drugs, on the molecular networks that define these states. In this article, we describe how such an approach offers a novel way to understand biology, characterize disease and ultimately develop improved therapies, and discuss the challenges to realizing these goals.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Descoberta de Drogas/legislação & jurisprudência , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Humanos , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismoRESUMO
In spite of the therapeutic importance of endoderm derivatives such as the pancreas, liver, lung, and intestine, there are few molecular markers specific for early endoderm. In order to identify endoderm-specific genes as well as to define transcriptional differences between definitive and visceral endoderm, we performed microarray analysis on E8.25 definitive and visceral endoderm. We have developed an early endoderm gene expression signature, and clarified the transcriptional similarities and differences between definitive and visceral endoderm. Additionally, we have developed methods for flow cytometric isolation of definitive and visceral endoderm. These results shed light on the mechanism of endoderm formation and should facilitate investigation of endoderm formation from embryonic stem cells.
