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MUSERGEN: MultiUSER equipment for GENe identification in biosciences and biotechnology

MUSERGEN：用于生物科学和生物技术中基因识别的多用户设备

基本信息

批准号：
BB/T017481/1
负责人：
Douglas Kell
金额：
$ 36.57万
依托单位：
University of Liverpool
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FT017481%2F1
关键词：
MUSERGEN MultiUSER equipment GENe identification

项目摘要

Improving our understanding of biology is largely accomplished by natural or laboratory manipulation of the sequences of genes (and hence proteins), and observations of the effects on the organisms of interest. Such effects can include tolerance to various stresses, the ability to metabolise compounds of interest, the ability to improve longevity, to remain healthy, and so on. In principle one might do this many times to produce vast libraries of variants. If the organism is one that makes a product of interest (e.g. penicillin, a biofuel, or indeed anything else), this also leads to the possibility of improving the host's productivity dramatically. In practice, most methods are able only to remove (knock out) the activity of genes, but fewer can be used to manipulate them in a graded manner, and this tends to be done in a bespoke or 'craft' industry kind of way. More recently, it was discovered that a system of 'immune defence' for bacteria against certain viruses, known as CRISPR-Cas9, allows a much more precise 'gene editing', and this general strategy is revolutionising biology. Again, however, the edits tend to be done one at a time.Very recently (October 1st, 2019), an instrument became available that is able to perform such gene editing on a genome-wide scale, allowing thousands of such experiments effectively to be done at once (in parallel). It uses a version of CRISPR-Cas9 with its own proprietary system (but one that is entirely free for commercial use). By tagging each known edit with a barcode, and assessing the frequency with which particular barcodes are expressed under a condition of interest, one can assess the relative importance of hundreds of genes simultaneously, and how they should be modified. This instrument is designed to 'democratise' CRISPR-based gene editing, and it is known as the Inscripta Onyx instrument. The purpose of this proposal is to obtain funds to purchase such an instrument, to set it up in Liverpool's synthetic biology centre (the Gene Mill in the Centre for Genomic Research), and to make it available to the local and wider BBSRC community.The result of this program will be huge amounts of new knowledge of which genes - which will often be unexpected ones - are involved in various bioprocesses of interest. It will allow us to control and optimize cellular enzyme and small molecule production in a truly rational manner.

提高我们对生物学的理解主要是通过自然或实验室操纵基因序列（以及蛋白质），以及观察对感兴趣的生物体的影响来实现的。这些效应包括对各种压力的耐受性、代谢感兴趣的化合物的能力、延长寿命的能力、保持健康的能力等等。原则上，人们可以多次这样做，以产生大量的变异库。如果生物体是一种生产感兴趣的产品（例如青霉素，生物燃料或其他任何东西）的生物体，这也可能大大提高宿主的生产力。在实践中，大多数方法只能去除（敲除）基因的活性，但很少有方法可以用来以分级的方式操纵它们，而且这往往是以定制或“工艺”行业的方式完成的。最近，人们发现细菌对某些病毒的“免疫防御”系统，称为CRISPR-Cas9，允许更精确的“基因编辑”，这种通用策略正在彻底改变生物学。然而，编辑往往是一次完成一个。最近（2019年10月1日），一种能够在全基因组范围内进行这种基因编辑的仪器问世，允许同时（并行）有效地完成数千个这样的实验。它使用了一个CRISPR-Cas9版本，带有自己的专有系统（但完全免费用于商业用途）。通过用条形码标记每个已知的编辑，并评估特定条形码在感兴趣的条件下表达的频率，人们可以同时评估数百个基因的相对重要性，以及它们应该如何被修饰。该仪器旨在“民主化”基于CRISPR的基因编辑，它被称为Inscripta Onyx仪器。该计划的目的是获得资金购买这样一台仪器，将其安装在利物浦的合成生物学中心（基因组研究中心的基因磨坊），并将其提供给当地和更广泛的BBSRC社区。该计划的结果将是大量的新知识，即哪些基因（通常是意想不到的基因）参与了各种感兴趣的生物过程。它将使我们能够以真正合理的方式控制和优化细胞酶和小分子的生产。