21ENGBIO_De Novo protein scaffolds for uranium decontamination

21ENGBIO_用于铀净化的De Novo蛋白质支架

• 批准号: BB/W013061/1
• 负责人: Louise Natrajan
• 金额: $ 12.68万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW013061%2F1
• 关键词: 21ENGBIO_De; Novo; protein; scaffolds; uranium

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.

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。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导致人们迫切需要使用碳中和的能源。在创建脱碳电力行业的过程中，可再生能源是大多数人关注的焦点。根据英国政府商业、能源和工业战略部（BEIS）的数据，目前提供英国约20%电力的铀核裂变能源在生产时被归类为零碳能源。事实上，法国电力公司（EDF）和意昂集团（E.ON）等能源公用事业供应商现在已将核能纳入其可再生能源组合。然而，公众对核能的接受和继续使用在很大程度上取决于未来对核废料的退役和清理的持续投资，包括现有遗留废料的大量储存。因此，以铀为主要成分的放射性废料的安全管理是确保核能未来安全的重要推动因素。英国目前的政策是在地下地质处置设施中处置其高放射性废物，在地上低放射性废物处置库（LLWR，坎布里亚郡）处置其低放射性废物（包括铀和医用放射性同位素）。然而，到本十年末，英国15座反应堆中的8座将达到其生命周期的终点，任何退役和新建（目前计划）及其相关废物都需要严格的安全案例。然而，为了实现这一目标，为了实施应对这一重大环境挑战的全系统解决方案，必须开展基础研究，确保长期遏制废物。为了解决这些紧迫的问题，我们建议利用合成生物学的优势，对新的蛋白质衍生材料进行生物工程，这些材料可以自组装成三螺旋“卷曲线圈”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性质。合成肽支架为构建预先组织的金属三维结合环境提供了一种极好的方法，其灵感来自于在天然金属蛋白中观察到的高度选择性配合，但无需通过诱变制造重组蛋白的艰巨任务。这种结构可以通过氨基酸序列的特定工程来预测地操纵和控制，以系统地优化结合。这样，就可以在实地监测60多年来民用核人为活动产生的自然和工程环境中的铀流动性。我们将首先对肽序列进行生物工程，使其结构可以形成螺旋，并表现出蛋白质类型的三级和四级结构，与环境条件（例如pH波动）兼容，其结合位点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，然后将它们封装/附着到材料（例如聚合物，磁性颗粒）上，以创建双传感器和去污设备。主要目标是开发新的材料、技术和基于光谱的工具，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污染材料库存，以提高核电作为关键碳中和能源的可持续性，符合2050年净零碳议程。