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

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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.