Harness optogenetic control and real-time analysis of chemicals production in bioreactors

英国化学工业对英国经济至关重要，年销售额超过500亿GB，雇用15.8万人，是英国最大的出口行业之一，贸易顺差。由于大约8%的化石燃料消费用于生产化学品(包括药品)，社会需要新技术来生产现代生活所必需的药品、化学品和材料，以与化石燃料脱钩的方式。替代的生物制造路线将允许几乎任何含碳材料转化为这些现代必需品。建立这种“高价值生物经济”是曼彻斯特生物技术研究所研究计划的核心。这个博士研究生通过开发创新的发酵平台，使用工程微生物菌株和光遗传反馈控制，为基于生物的精细和特种化学品的生产做出贡献。该项目设在曼彻斯特合成生物学中心SYNBIOCHEM，该中心为微生物菌株工程建立了完全集成和自动化的平台，用于生产精细和特殊的化学品。1这是一个令人兴奋的项目，旨在通过发酵过程中依赖光的转录控制，建立代谢途径流量的反馈控制，利用光遗传控制和实时分析生物反应器中的化学品生产。学生将获得最先进的合成生物学方法的经验，包括微生物菌株工程、生物部件工程和表征、通过实验室发酵生产化学品、使用创新的质谱学方法对发酵顶端积累的产品进行采样，以及通过人工智能/机器学习组件的光遗传反馈控制这些发酵的结果。这位在曼彻斯特生物科技学院(MIB)的博士生和位于MIB的SYNBIOCHEM合成生物学研究中心将由Nigel Srutton教授、Eriko Takano教授和Sam Hay博士共同指导，高级实验主任Derren Heyes博士和Kat好莱坞博士将提供专家科学/技术支持。学生将接受“湿”生物技术的广泛方面的培训，包括合成生物学、微生物菌株生物工程、分子生物学、创新的质谱学和分析，以及包括人工智能/机器学习在内的“干”科学，以及生物反应器反馈控制的计算编码的更广泛方面。这个项目将适合对生物工程、化学品生产和工业生物技术未来职业感兴趣的个人。这个博士项目将通过提供与生物能源和工业生物技术主题相关的各种方法的培训来开拓新的工作方式。这将包括基于实验室的技能，在菌株生物工程，光遗传蛋白成分的设计，建造和测试，数据处理和统计分析，HTP分析方法，生物反应器设计和工程，以及控制回路工程。这将为博士生提供使用和应用量化数据驱动的方法来更全面地理解生物学问题并将其应用于扩大规模/生产挑战的能力。除了培训之外，研究项目目标/产出本身将采用新的工作方式，因为它们将为生产高价值精细化学品和材料提供创新的工具和技术途径。

The UK chemical industry is vitally important to the UK economy, with annual sales over £50bn, employing 158,000 people and is one of the UK's largest exporting industries with a positive trade balance. Since around 8% of fossil fuel consumption is used to produce chemicals (including pharmaceuticals), society needs new technologies to manufacture the pharmaceuticals, chemicals and materials essential to modern life, in ways that are decoupled from fossil fuels. Alternative biomanufacturing routes will allow virtually any carbon containing material to be converted into these modern-day essentials. Building this 'High Value Bioeconomy' is at the core of research programmes in the Manchester Institute of Biotechnology. This PhD studentship contributes to this vision by developing innovative fermentation platforms for the bio-based production of fine and speciality chemicals using engineered microbial strains and optogenetic feedback control. The project is set in the Manchester Centre for Synthetic Biology SYNBIOCHEM which has set up fully integrated and automated platforms for microbial strain engineering for the production of fine and speciality chemicals.1This is an exciting project that seeks to harness optogenetic control and real-time analysis of chemicals production in bioreactors by setting up feedback control of metabolic pathway flux through light-dependent transcriptional control during fermentation. The student will get experience of state-of-the-art synthetic biology methods in microbial strain engineering, biological parts engineering and characterisation, chemicals production through laboratory fermentations, the use of innovative mass spectrometry methods to sample product build up in the headspace of fermentations and control of the outcome of these fermentations through optogenetic feedback control with AI/machine learning components. The PhD student based in Manchester Institute of Biotechnology (MIB) and the SYNBIOCHEM Synthetic Biology Research Centre in the MIB will be co-supervised by Professor Nigel Scrutton, Prof Eriko Takano and Dr Sam Hay, with expert scientific/technical support from Senior Experimental Officers Dr Derren Heyes and Dr Kat Hollywood. The student will be trained in broad aspects of 'wet' biotechnology, including synthetic biology, microbial strain bioengineering, molecular biology, innovative mass spectrometry and analytics, and also 'dry' science including AI/machine learning and broader aspects of computational coding for bioreactor feedback control. This project would suit individuals interested in future careers in bioengineering, chemicals production, and industrial biotechnology.This PhD project will exploit new ways of working by providing training in a variety of approaches relevant to the Bioenergy and Industrial Biotechnology theme. This will include lab-based skills in strain bioengineering, design, build and testing of optogenetic protein components, data processing and statistical analysis, HTP analytical methods, bioreactor design and engineering, and control loop engineering. This will provide the PhD student with the ability to use and apply quantitative data-driven approaches to more fully understand biological questions and apply these to scale up/production challenges. In addition to the training the research project goals/outputs in themselves will exploit new ways of working, as they will provide innovative tools and technological approaches for the production of high-value fine chemicals and materials