权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A DNA Synthesis and Construction Foundry for Synthetic Biology @ Imperial College

帝国理工学院合成生物学 DNA 合成和构建铸造厂

基本信息

批准号：
BB/L027852/1
负责人：
Paul Freemont
金额：
$ 263.76万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FL027852%2F1
关键词：
DNA Synthesis Construction Foundry Synthetic

项目摘要

Synthetic biology is an emerging field that brings together biological scientists and engineers with the aim of developing new systematic ways to build and design biological systems and cells for useful purposes. Biological cells can carry out a vast array of functions when driven by instructions. These instructions are encoded by DNA much like a computer is controlled by software. By analogy, the DNA in a cell can be considered as the cell's software or operating system - containing the genetic instruction set (genome) for different types of cells and organisms. The code of DNA is composed of four complementary chemical building blocks called nucleotide bases (G, C, A and T) linked together in a sequence and these building blocks pair up specifically (G-C and A-T) such that the two interwoven strands of DNA forms a helical repeating structure. The beauty of DNA is such that a single strand can act as a template for the other strand so that it can be easily copied and replicated. How is the DNA code decoded by the cell? The instructions encoded within DNA are decoded by two biochemical processes called transcription and translation. Transcription results in one strand of DNA being copied to produce an intermediary messenger molecule (mRNA) and translation results in the production of proteins coded for by the mRNA with each 3 nucleotide unit (codon) specifying a particular amino acid which is the basic building block for proteins. There are 20 different amino acid building blocks and depending on the sequence of the DNA, which directs which amino acids are linked together, fold into complex 3D structures that perform specific functions. Proteins are, in essence, the cellular machines that carry out all of the necessary chemical reactions for life, e.g. the conversion of food sources like sugar into energy. Over the last 20 years technological advances have resulted in the routine ability to 'read' the DNA code - deciphering, essentially, the genetic instruction sets (proteins) for every major living organism on Earth. These DNA sequences can run into many hundreds of thousands of base units written as GCATGCCCTTTAGCTA etc. They encode the basic code to make proteins for a specific organism. More recent technology advances have now resulted in our ability to chemically synthesise DNA or 'write' DNA in a test tube. Synthetic biology aims to establish a proper systematic engineering framework that will allow researchers to design and write DNA tailored to specific human-defined applications, such that these new synthetic DNA sequences can be inserted into laboratory cells to perform specific functions. The aim of this proposal is to make the 'writing' of DNA streamlined and more automated at an industrial scale - such that tens of thousands of designed DNA constructions can be build and tested routinely as engineers would prototype a design. To do this we will establish a DNA synthesis and construction foundry that will comprise a number of robotic and lab-based instruments that will allow the design and testing of synthetic biology constructions to be carried out routinely and in a safe way under a controlled laboratory environment.

合成生物学是一个新兴的领域，汇集了生物科学家和工程师，旨在开发新的系统方法来构建和设计生物系统和细胞。生物细胞在指令的驱动下可以执行大量的功能。这些指令由DNA编码，就像计算机由软件控制一样。通过类比，细胞中的DNA可以被认为是细胞的软件或操作系统-包含不同类型细胞和生物体的遗传指令集（基因组）。DNA的密码由四个互补的化学结构单元组成，称为核苷酸碱基（G，C，A和T），它们以序列连接在一起，这些结构单元特异性配对（G-C和A-T），使得DNA的两条交织链形成螺旋重复结构。DNA的美妙之处在于，一条单链可以作为另一条链的模板，这样它就可以很容易地复制和复制。 DNA密码是如何被细胞解码的？DNA中编码的指令通过两个生化过程解码，称为转录和翻译。转录导致DNA的一条链被复制以产生中间信使分子（mRNA），并且翻译导致由mRNA编码的蛋白质的产生，其中每3个核苷酸单元（密码子）指定特定的氨基酸，其是蛋白质的基本构建单元。有20种不同的氨基酸构建块，并根据DNA的序列，指导哪些氨基酸连接在一起，折叠成执行特定功能的复杂3D结构。蛋白质本质上是细胞机器，执行生命所需的所有化学反应，例如将糖等食物转化为能量。在过去的20年里，技术进步已经导致了“阅读”DNA代码的常规能力-破译，基本上，地球上每个主要生物体的遗传指令集（蛋白质）。这些DNA序列可以运行到几十万个碱基单位写为GCATGCCCTTTAGCTA等他们编码的基本代码，使蛋白质为特定的有机体。最近的技术进步已经使我们能够化学合成DNA或在试管中“写入”DNA。合成生物学旨在建立一个适当的系统工程框架，使研究人员能够设计和编写针对特定人类定义应用的DNA，以便这些新的合成DNA序列可以插入实验室细胞中以执行特定功能。这项提案的目的是使DNA的“写作”在工业规模上更加精简和自动化-这样成千上万的设计DNA结构可以在工程师设计原型时进行常规构建和测试。为此，我们将建立一个DNA合成和构建铸造厂，其中将包括一些机器人和基于实验室的仪器，这些仪器将允许合成生物学构建的设计和测试在受控的实验室环境下以常规和安全的方式进行。