21ENGBIO_De Novo protein scaffolds for uranium decontamination

能源的可持续性无疑是本世纪世界面临的最具挑战性和最紧迫的社会经济问题之一。由于燃烧化石燃料导致二氧化碳排放量增加，与气候变化灾害相关的问题已经导致迫切需要使用碳中性的能源。在创建一个脱碳的电力部门，可再生能源是大多数人心目中的最前沿。在这里，根据政府商业、能源和工业战略部（BEIS）的说法，目前提供英国约20%电力的铀核裂变能源在生产点被归类为零碳能源。事实上，EDF和E.ON等能源公用事业提供商现在将核能纳入其可再生能源组合。然而，公众接受和继续使用核能在很大程度上取决于未来对退役和清理所产生的核废物，包括大量储存的现有遗留废物的持续投资。因此，安全管理放射性废物-铀是其中的主要质量成分-是确保核能未来安全的一个重要手段。联合王国目前的政策是在地下地质处置设施处置高放射性废物，在地面低放射性废物处置库（坎布里亚郡低放射性废物处置库）处置低放射性废物（包括铀和医用放射性同位素）。然而，英国15个反应堆中的8个将在本十年结束时达到其生命周期的终点，任何退役和新建（目前计划的）及其相关废物都需要伴随严格的安全案例。然而，为了实现这一目标，必须进行基础研究，以确保长期的废物控制，以便实施应对这一重大环境挑战的整体系统解决方案。为了解决这些紧迫的问题，我们建议利用合成生物学的生物工程新的蛋白质衍生的材料，自组装成一个三重螺旋的“卷曲螺旋”荧光结构，以螯合环境水平的铀与前所未有的选择性，并报告其浓度和化学使用荧光读出信号。合成肽支架提供了一个很好的方法来建立预先组织的，三维的金属结合环境，灵感来自于在天然金属蛋白中观察到的高度选择性的协调，但没有经常，通过诱变创建重组蛋白质的艰巨任务。这样的结构可以通过氨基酸序列的特异性工程化来可预测地操纵和控制，以系统地优化结合。通过这种方式，可以在实地监测60多年来民用核人为活动产生的铀在自然和工程环境中的流动性。我们将首先生物工程肽序列，其结构可以形成螺旋并显示蛋白质类型的三级和四级结构，与环境条件（例如pH波动）相容，并且其结合位点倾向于选择性地结合铀而不是其他无所不在的金属离子和化学实体，如碳酸盐和磷酸盐。然后，我们将在分子动力学建模模拟的帮助下，以迭代方式修改设计，以在将其封装/附着到材料（例如聚合物，磁性颗粒）之前优化结合特性，以创建双传感器和去污设备。其主要目标是开发新的材料，技术和基于光谱的工具，以帮助管理英国的放射性废物和污染材料的重要库存，通过应用新的生物回收和生物修复工具包，以提高核电的可持续性作为一个关键的碳中性能源符合2050年净零碳议程。

Energy sustainability is indisputably one of the most challenging and pressing socioeconomic problems facing the world this century. Problems associated with climate change disasters from increasing CO2 emissions by the burning of fossil fuels has led to a desperate need to use energy sources that are carbon neutral. In creating a decarbonised power sector, renewable energy sources are at the forefront of most people's minds. Here, energy from uranium nuclear fission, that currently provides around 20% of the UK's electricity, is classified as a zero carbon energy source at the point of production according to the Governments' Department for Business, Energy & Industrial Strategy (BEIS). Indeed, energy utility providers such as EDF and E.ON now include nuclear in their renewable energy portfolio. However, public acceptance and the continued use of nuclear power is heavily reliant on sustained future investment in decommissioning and clean-up of generated nuclear wastes including the large stockpile of existing legacy wastes. The safe management of radioactive wastes, where uranium is the major component by mass, is thus a vital enabler for a secure nuclear energy future. Current UK policy is to dispose of its higher activity radioactive wastes in the subsurface in a geological disposal facility, and lower level radioactive wastes (including uranium and medical radioisotopes) above ground in the Low Level Waste Repository (LLWR, Cumbria). However, 8 of the UK's 15 reactors will reach the end of their lifecycle by the end of this decade and any decommissioning and new builds (currently planned) and their associated wastes need to be accompanied by rigorous safety cases. However, to achieve this, underpinning research to ensure long term waste containment is essential in order to implement whole systems solutions to this major environmental challenge. To address these pressing issues, we propose to take advantage of synthetic biology to bioengineer new protein derived materials that self-assemble into a triple helical 'coiled coil' fluorescent structures in order to both sequester environmental levels of uranium with unprecedented selectivity, and to report on its concentration and chemical using fluorescent read out signals. Synthetic peptide scaffolds offer an excellent approach to building preorganised, three-dimensional binding environments for metals, inspired by the highly selective coordination observed in natural metalloproteins but without the often, arduous task of creating recombinant proteins through mutagenesis. Such structures can be predictably manipulated and controlled by specific engineering of the amino acid sequence, to systematically optimise binding. In this way, uranium mobility in the natural and engineered environment from over 60 years of civil nuclear anthropogenic activities can be monitored in the field. We will first bioengineer peptide sequences, whose structures can form helices and exhibit protein type tertiary and quaternary structures, are compatible with the environmental conditions (e.g. pH fluctuations), and whose binding sites are predisposed to selectively bind uranium over other omnipresent metal ions and chemical entities such as carbonates and phosphates. We will then modify the design in an iterative fashion with help from molecular dynamics modelling simulations to optimise the binding properties before encapsulating/attaching them to materials (e.g. polymers, magnetic particles) to create dual sensor and decontamination devices. The key goal is to develop new materials, technology and spectroscopic based tools to help manage the UK's significant inventory of radioactive wastes and contaminated materials by applying a new bio-recycling and bioremediation tool kit to increase the sustainability of nuclear power as a key carbon neutral energy source in line with the 2050 net zero carbon agenda.