Transcriptional Regulatory Element Functional Genomics Equipment

在过去的13年里，我在多伦多大学建立了一个由NSERC资助的解码哺乳动物调控基因组的项目，该项目支持科学发现和84 HQP的培训。我要求建立一个全面的转录调控元件功能基因组学系统。这个系统将允许我们目前的方法从细胞扩展到整个有机体。如果没有这些设备，我的NSERC资助的研究计划和相关的HQP培训将受到严重影响。由该系统支持的研究旨在揭示使用计算和功能基因组学方法管理哺乳动物基因组功能的调控机制。尽管人类基因组序列在近20年前就完成了，但我们目前还无法确定该序列中绝大多数的功能。我们知道如何阅读基因编码区内的序列密码，但这些基因组的98%是基因调控元件，在特定细胞中打开/关闭基因。尽管我们知道基因调控元件对复杂生物体的正常发育很重要，而且往往是不同物种身体规划特定差异的原因，但我们对赋予它们功能的序列密码知之甚少。这就像是用一种你看不懂的语言写的书。或者，因为我们已经对100多种哺乳动物的基因组进行了完整的测序，整个图书馆的书籍都是你不能阅读的。转录调控元件功能基因组学所要求的系统包括数据分析工作站、实时PCR机、用于样品制备的冷冻离心机和小鼠胚胎电穿孔设备。这台设备对我的研究计划和HQP的培训至关重要。目前，我们的工作能够研究细胞中的基因表达，但不能研究整个哺乳动物生物体中的基因表达。所要求的设备将使我们能够研究在发育过程中在特定组织中起作用的基因调控元件。从长远来看，完全解码基因组序列将使我们能够预测调控序列的变化如何影响特定基因的表达。这将对我们理解种群的发育、进化和表型变异的根本原因产生广泛的影响。

Over the past 13 years I have established an NSERC funded Program for Decoding the Mammalian Regulatory Genome at the University of Toronto that has supported scientific discoveries and training for 84 HQP. I am requesting a comprehensive system for Transcriptional Regulatory Element Functional Genomics. This system will allow for an expansion of our current approach from cells to a whole organism. Without this equipment, my NSERC funded research program and associated HQP training will be severely impacted. Research supported by this system aims to uncover the regulatory mechanisms that govern mammalian genome function using both computational and functional genomics approaches. Despite completion of the human genome sequence almost 20 years ago we are currently not able to determine the function of the vast majority of this sequence. We understand how to read the sequence code within gene coding regions but these are 98% of the genome are gene regulatory elements that turn genes on/off in specific cells. Although we know gene regulatory elements are important for the proper development of complex organisms and are often the cause of specific differences in the body plan of different species, we know remarkably little about the sequence code that gives them their function. This is like having a book written in a language you can't read. Or, as we have fully sequenced genomes for more than 100 mammals, an entire library of books that you can't read. The requested system for Transcriptional Regulatory Element Functional Genomics includes a data analysis workstation, real-time PCR machine, chilled centrifuge for sample preparation and a mouse embryo electroporation device. This equipment is critical to my research program and the training of HQP. At the moment our work is able to investigate gene expression in cells but not in whole mammalian organisms. The requested equipment will allow us to investigate gene regulatory elements that are functional in specific tissues during development. In the long term, fully decoding genome sequences will allow us to predict how regulatory sequence changes can affect the expression of specific genes. This will have widespread impact on our understanding of development, evolution and the underlying cause of phenotype variation in populations.