Genome architecture and expression

随着数以千计的基因组被测序，甚至更多的基因组进入测序管道，基因组学时代的下一个主要挑战是了解基因组序列如何指导活着的有机体中的基因表达，从而决定生物和行为。我的研究计划就是为了直接应对这一挑战而设计的。特别是，我将利用密切相关物种的基因组序列来识别保守的序列块(也称为同步性块)和基因组重排事件。我将着重比较分析一种名为秀丽线虫的小型土壤线虫的基因组，以及其他四种线虫的基因组：布氏线虫、雷曼线虫、布伦纳线虫和日本线虫。对线虫的研究揭示了生物过程的关键秘密。事实上，在过去的六年里，六名科学家因使用线虫作为模型系统的工作而获得诺贝尔奖。我的研究计划建立在一个假设的基础上，即功能上重要的基因组序列块在不同的物种中将保持保守。基因组保守信息将被用来理解通过对线虫样本中的表达信息进行测序而获得的基因表达数据。我将研究不同基因组块中基因的相关性，以及它们在不同发育阶段和细胞类型中的表达情况。此外，我将探索线虫基因组表达的转录调控。与DAF-19合作，DAF-19是一种保守的转录因子，可以在广泛的物种中找到，我将继续探索基因组-一组由共同转录因子调控的基因-是如何受到调控的，旨在深入了解基因在基因组水平上的转录调控。具体地说，我将研究启动子密码，了解它将有助于识别目的基因以及分化和发育。这个研究项目汇集了生物信息学、功能基因组学、比较基因组学和分子生物学的方法，以揭开基因组表达的秘密，特别是这一生物过程的潜在机制。

With thousands of genomes being sequenced and even more entering the sequencing pipeline, the next major challenge in the era of genomics is to understand how the genome sequence directs gene expression in living organisms, thereby dictating biology and behavior. My research program has been designed to tackle this challenge directly. In particular, I will take advantage of the genome sequences of closely related species to identify conserved sequence blocks (also known as synteny blocks) and genome rearrangement events. I will focus on the comparative analysis of the genome of a small soil dwelling nematode worm called Caenorhabditis elegans (C. elegans) and the genomes of four other Caenorhabditis species: C. briggsae, C. remanei, C. brenneri, and C. japonica. Research on C. elegans has revealed critical secrets of biological processes. Indeed, in the last six years, six scientists have won Nobel prizes for their work using C. elegans as a model system. My research program builds on the assumption that functionally important genome sequence blocks will remain conserved in different species. The genome conservation information will be used to understand gene expression data acquired by sequencing the expressed messages in C. elegans samples. I will examine the correlation of genes within different genome blocks, and their expression profiles in different developmental stages and cell types. Furthermore, I will explore transcriptional regulation of C. elegans genome expression. Working with DAF-19, a conserved transcription factor that can be found in a wide range of species, I will continue to explore how a gene battery -- a set of genes that are regulated by a common transcription factor -- is regulated, aiming to gain insight into the transcriptional regulation of genes at the genome scale. Specifically, I will investigate the promoter code, the understanding of which will shed light on the identification of target genes and differentiation and development. This program of research brings together methods in bioinformatics, functional genomics, comparative genomics and molecular biology to unravel the secret of genome expression and, in particular, the underlying mechanisms of this biological process.