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

合成生物学是一个新兴的领域，它汇集了生物科学家和工程师，目的是开发新的系统方法来构建和设计生物系统和细胞。在指令的驱动下，生物细胞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——包含不同类型的细胞和生物体的遗传指令集（基因组）。DNA的密码是由四个互补的化学构建模块组成的，称为核苷酸碱基（G， C， A和T）按顺序连接在一起，这些构建模块特别配对（G-C和A-T），这样两个相互交织的DNA链就形成了螺旋重复结构。DNA的美妙之处在于，单链可以作为另一条链的模板，这样它就可以很容易地被复制和复制。细胞是如何解码DNA密码的？编码在DNA内的指令通过两个生化过程解码，称为转录和翻译。转录导致一条DNA链被复制以产生中间信使分子（mRNA），翻译导致产生由mRNA编码的蛋白质，每个3个核苷酸单位（密码子）指定一个特定的氨基酸，这是蛋白质的基本组成部分。有20种不同的氨基酸构建模块，根据DNA的序列，哪些氨基酸连接在一起，折叠成复杂的3D结构，执行特定的功能。从本质上讲，蛋白质是细胞机器，它执行生命所需的所有化学反应，例如将糖等食物来源转化为能量。在过去的20年里，技术的进步已经导致了“阅读”DNA密码的常规能力——从本质上讲，破译地球上每一个主要生物的遗传指令集（蛋白质）。这些DNA序列可以形成成千上万的碱基单位，如GCATGCCCTTTAGCTA等。它们编码为特定生物体制造蛋白质的基本代码。最近的技术进步已经使我们能够在试管中化学合成DNA或“写入”DNA。合成生物学的目标是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适合特定人类定义应用的DNA，这样这些新的合成DNA序列就可以插入实验室细胞中执行特定功能。这项提议的目的是使DNA的“书写”在工业规模上变得更加精简和自动化——这样，成千上万的设计好的DNA结构就可以被构建和测试，就像工程师将设计原型一样。为此，我们将建立一个DNA合成和构建铸造厂，该铸造厂将包括许多机器人和基于实验室的仪器，这些仪器将允许在受控的实验室环境下以常规和安全的方式进行合成生物学结构的设计和测试。

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.