Bilateral NSF/BIO-BBSRC: Synthetic DNA Nanopores for Selective Transmembrane Transport

双边 NSF/BIO-BBSRC：用于选择性跨膜运输的合成 DNA 纳米孔

• 批准号: BB/N017331/1
• 负责人: Stefan Howorka
• 金额: $ 52.17万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN017331%2F1
• 关键词: Bilateral; NSF; BIO; BBSRC; Synthetic

Synthetic biology is a discipline with the bold aim to expand the scope of nature. It sees biology from the perspective of an engineer and asks how existing biomolecular structures, cellular processes or cells can be altered with the objective to achieve benefits in applications. These can range from biosensing over biomedicine to biocatalysis. An example is the engineering of a thermally stable enzyme that is used in a washing detergent. The higher aim is, however, not to replace small parts of an enzyme but to completely redesign cellular components or make them from scratch. This can be advantageous as it gives more control over the properties of the new synthetic products.Our project falls within this category of synthetic biology. We will create synthetic versions of membrane proteins from the bottom up. Natural membrane proteins are important as they are involved in many aspects of life including the neural function, the perception of sensations, and the development of an immune response. Replicating some of the functions is however challenging with traditional building materials such as polypeptides. The issue is that the polypeptide chains do not always fold in the correct anticipated structures.We will use DNA as a construction material to overcome the problem. DNA's natural role is to carry genetic information. It is composed of duplex of two strands held together by base pairs. But scientists have since discovered that the base pairing can be used to form non-natural structures. Here we will produce a series of nanopores composed of DNA. The novelty is that the pores will achieve unprecedented control over transport across membranes. The new nanoscale pores will validate the concept that DNA is a suitable material. In addition, the pores will be exploited to build synthetic membrane compartments that can be used in cell biological research, or for the development of new anti-cancer drug systems.

合成生物学是一门具有扩大自然界范围的大胆目标的学科。它从工程师的角度来看待生物学，并询问如何改变现有的生物分子结构、细胞过程或细胞，以期在应用中获得好处。它们的范围从生物医学上的生物传感到生物催化。一个例子是在洗涤剂中使用的一种热稳定酶的工程。然而，更高的目标不是取代一种酶的一小部分，而是完全重新设计细胞成分或从头开始制造它们。这可能是有利的，因为它可以更多地控制新合成产品的性质。我们的项目属于这一类合成生物学。我们将自下而上创建膜蛋白的合成版本。天然膜蛋白很重要，因为它们涉及生活的许多方面，包括神经功能、感觉感知和免疫反应的发展。然而，用多肽等传统建筑材料复制一些功能是具有挑战性的。问题是多肽链并不总是以正确的预期结构折叠。我们将使用DNA作为结构材料来克服这个问题。DNA的天然作用是携带遗传信息。它由两条由碱基对连接在一起的双链组成。但科学家后来发现，碱基配对可以用来形成非自然结构。在这里，我们将生产一系列由DNA组成的纳米孔。新奇之处在于，毛孔将实现对跨膜运输的前所未有的控制。新的纳米尺度的毛孔将证实DNA是一种合适的材料的概念。此外，这些毛孔将被用来构建可用于细胞生物学研究或开发新的抗癌药物系统的合成膜隔间。

项目成果

Dynamic Interactions between Lipid-Tethered DNA and Phospholipid Membranes.

• DOI: 10.1021/acs.langmuir.8b02271
• 发表时间: 2018-12-11
• 期刊: Langmuir : the ACS journal of surfaces and colloids
• 作者: Arnott PM;Joshi H;Aksimentiev A;Howorka S
• 通讯作者: Howorka S

Structure and dynamics of an archetypal DNA nanoarchitecture revealed via cryo-EM and molecular dynamics simulations.

• DOI: 10.1038/s41467-023-38681-5
• 发表时间: 2023-06-19
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Ahmad, Katya;Javed, Abid;Lanphere, Conor;Coveney, Peter V.;Orlova, Elena V.;Howorka, Stefan
• 通讯作者: Howorka, Stefan

A reversibly gated protein-transporting membrane channel made of DNA.

• DOI: 10.1038/s41467-022-28522-2
• 发表时间: 2022-04-28
• 期刊: Nature communications
• 影响因子: 16.6