Developing and investigating an ultra-stable molecular hub for bionanotechnology

当生物学家希望分离或固定一个物体（蛋白质、DNA、RNA、糖、小有机分子、纳米颗粒）时，他们通常会将维生素生物素附着在这个物体上，这样物体就可以被链亲和素蛋白捕获。从生物素到链霉亲和素的联系是自然界已知的最紧密的联系之一，但这种联系在具有挑战性的情况下可能被打破，因此限制了许多生物实验和设备。我们已经改变了链亲和素，它与生物素形成了更强的联系，因此生物素被捕获的时间更长，并在更恶劣的条件下保持结合。我们计划在原子水平上确定为什么这种新的相互作用更强。这一见解将有助于阐明超强结合的基础，从而帮助设计能够更稳定地与靶标结合从而更有效的药物。我们还将设计链亲和素，使其能够锚定两种不同的分子，使生物学家能够创建新的组装来组合和控制生物分子的功能。我们自己将使用这些组件来探索生长因子如何在细胞内的信号传递中协同工作或竞争，从而决定细胞是活是死还是分裂。

When biologists wish to isolate or immobilise an object (proteins, DNA, RNA, sugars, small organic molecules, nanoparticles), they will very often attach the vitamin biotin to this object, so that the object can be captured by the protein streptavidin. The link from biotin to streptavidin is one of the strongest known in nature, but this link can be broken in challenging situations, so limiting many biological experiments and devices. We have made an altered streptavidin which forms an even stronger link to biotin, so that biotin is captured for longer and stays bound in harsher conditions. We plan to determine at the atomic level why this new interaction is stronger. This insight should help to illuminate the basis of ultra-strong binding, and so assist the design of drugs that can bind more stably to their targets and thus be more effective. We will also engineer streptavidin so that it can anchor two different kinds of molecules, enabling biologists to create new assemblies to combine and control the functions of biomolecules. We ourselves will use these assemblies to explore how growth factors can either work together or compete in transmitting signals inside the cell, so determining whether the cell lives, dies, or divides.