21ENGBIO_De Novo protein scaffolds for uranium decontamination

毫无疑问，能源可持续性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。化石燃料燃烧导致的二氧化碳排放量增加带来的与气候变化灾难相关的问题，导致人们迫切需要使用碳中性的能源。在创造一个脱碳的电力部门方面，可再生能源是大多数人最关心的问题。根据英国政府商业、能源和工业策略部(BEIS)的说法，铀核裂变产生的能源目前提供了英国约20%的电力，在生产时被归类为零碳能源。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投资组合。然而，公众对核电的接受和继续使用在很大程度上取决于今后在退役和清理产生的核废料方面的持续投资，包括现有遗留废料的大量储存。因此，放射性废物的安全管理是保障核能未来安全的关键因素，因为铀是放射性废物的主要质量成分。英国目前的政策是将其较高活性的放射性废物处置在地质处置设施的地下，并将较低水平的放射性废物(包括铀和医疗放射性同位素)处置在地面上的低水平废物储存库(坎布里亚省LLWR)。然而，英国15个反应堆中的8个将在本十年结束前结束其生命周期，任何退役和新建(目前计划的)及其相关废物都需要伴随着严格的安全案例。然而，要实现这一目标，确保长期控制废物的研究是必不可少的，以便实施应对这一重大环境挑战的整个系统解决方案。为了解决这些紧迫的问题，我们建议利用合成生物学对新的蛋白质衍生材料进行生物工程，这些材料自组装成一个三螺旋的“螺旋线圈”荧光结构，以便以前所未有的选择性隔离环境中的铀水平，并使用荧光读出信号报告其浓度和化学成分。合成多肽支架提供了一种为金属构建预先组织的三维结合环境的极佳方法，灵感来自于在天然金属蛋白中观察到的高度选择性的配位，但没有通过突变创造重组蛋白质的经常而艰巨的任务。这种结构可以通过对氨基酸序列的特定工程进行可预测的操纵和控制，从而系统地优化结合。通过这种方式，可以在野外监测60多年来民用核人为活动在自然和工程环境中的铀迁移情况。我们首先将生物工程多肽序列，其结构可以形成螺旋，呈现蛋白质类型的三级和四级结构，与环境条件(如pH波动)兼容，其结合部位倾向于选择性地结合铀，而不是其他无处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的方式修改设计，以优化结合性能，然后将其封装/附着到材料(例如聚合物、磁性颗粒)上，以创建双重传感器和去污设备。主要目标是开发基于新材料、技术和光谱的工具，通过应用新的生物回收和生物修复工具包来帮助管理英国大量的放射性废物和受污染材料，以增加核能作为关键碳中性能源的可持续性，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.