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Crossing biological membranes: Engineering the cell-environment interface to improve process efficiency

穿过生物膜：设计细胞-环境界面以提高过程效率

基本信息

批准号：
BB/L013703/1
负责人：
J Green
金额：
$ 119.34万
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FL013703%2F1
关键词：
Crossing biological membranes Engineering cell

项目摘要

Moving molecules across biological membranes represents a barrier to improving the efficiency of many existing Industrial Biotechnology and Bio-Energy (IBBE) processes that utilize cell factories. The reason for this is the perceived difficulties of working with membrane proteins and the often cell-toxic effects of the uncontrolled expression of transporters as well as the toxicity associated with the accumulation of products. Furthermore, with the advent of synthetic biology, identifying appropriate transport systems for integration into the regulatory and energetic networks of a chassis organism will be crucial in expanding the economic and social impacts of IBBE by facilitating the development of novel processes. The motivation for this network is that a deeper understanding of how substances are transported into, within, and out of cell factories will lead to the development of enabling technologies that are crucial for the future development of almost all cell-based IBBE applications, including the bottom-up design of systems (synthetic biology). This network proposal is timely because many proof-of-concept bio-production systems have been established, but few provide commercially acceptable product concentrations, often because the desired product proves to be toxic to the producing cell-factories. The goal is to develop innovative solutions and technologies to overcome yield restrictions, due to inefficient transport systems, in existing IBBE processes and to embed fully-integrated efficient transport systems into the design of the novel IBBE activities of the future. One the many strengths of this network bid is the cross-cutting nature of its focus such that its outputs will impact on almost all cell-factory-based IBBE processes. Thus our network is uniquely positioned to synergistically interact with other Networks in Industrial Biotechnology and Bioenergy (NIBB), as well as more widely. To achieve our goals we propose to assemble a managed five-year cross-disciplinary network of academics, industrial partners and other stakeholders to facilitate and deliver events to foster a multi-disciplinary knowledge-base focused on systems that transport substrates and products across membranes. This activity will lead to the creation of enabling technologies and biological systems with improved IBBE capacity.We envisage four major levels of activity within the network:1. We will create a cohesive community by bringing experts from different relevant disciplines together to share knowledge, identify key questions/bottlenecks, forge collaborations and create innovative solutions.2. We will support multi-disciplinary, collaborative research focussed on 'real' IBBE problems through a robust, competitive Proof-of-Concept funding program that includes biological, engineering and social scientific elements. 3. We will promote knowledge gathering and exchange through visits to participating laboratories and conference attendance.4. We will engage with the broader national and international research community, including other NIBBs to exchange knowledge and best practice, learned scientific societies and wider society via an interactive website and outreach events. We envisage five major outputs from the network:1. Enhanced interactions between academic institutions, IB companies and NIBBs to build partnerships that will channel wider research activity towards removing bottlenecks in existing IBBE processes and opening new IBBE opportunities.2. Identifying the major challenges presented by need for effective and efficient transport systems for the future development of synthetic biology based IBBE processes.3. Supporting the development of enabling technologies through Proof-of-Concept funding.4. Forming multi-disciplinary teams to compete in relevant funding calls promoting translational research activities.5. Creative early career scientists with networks of connections across academia and industry.

移动分子穿过生物膜代表了提高利用细胞工厂的许多现有工业生物技术和生物能源（IBBE）过程的效率的障碍。其原因是膜蛋白工作的困难和转运蛋白不受控制的表达的通常细胞毒性作用以及与产物积累相关的毒性。此外，随着合成生物学的出现，确定适当的运输系统整合到底盘有机体的监管和充满活力的网络将是至关重要的，在扩大IBBE的经济和社会影响，促进新工艺的发展。这个网络的动机是，更深入地了解物质如何被运输到细胞工厂，内部和外部，将导致开发对几乎所有基于细胞的IBBE应用的未来发展至关重要的使能技术，包括自下而上的系统设计（合成生物学）。这个网络的建议是及时的，因为许多概念验证的生物生产系统已经建立，但很少提供商业上可接受的产品浓度，往往是因为所需的产品被证明是有毒的生产细胞工厂。其目标是开发创新的解决方案和技术，以克服现有IBBE工艺中由于运输系统效率低下而造成的产量限制，并将完全集成的高效运输系统嵌入到未来新型IBBE活动的设计中。该网络竞标的众多优势之一是其重点的跨领域性质，其产出将影响几乎所有基于细胞工厂的IBBE流程。因此，我们的网络具有独特的优势，可以与工业生物技术和生物能源（NIBB）以及更广泛的其他网络协同互动。为了实现我们的目标，我们建议组建一个由学者，工业合作伙伴和其他利益相关者组成的五年期跨学科网络，以促进和提供活动，以培养一个多学科的知识库，重点是跨膜运输基质和产品的系统。这项活动将导致创建使能技术和生物系统，提高IBBE能力。我们设想网络内的四个主要活动级别：1.我们将通过将不同相关学科的专家聚集在一起来创建一个有凝聚力的社区，以分享知识，确定关键问题/瓶颈，建立合作关系并创建创新解决方案。我们将通过一个强大的，有竞争力的概念验证资助计划，包括生物，工程和社会科学元素，支持多学科，合作研究集中在“真实的”IBBE问题。3.我们将通过访问参与实验室和参加会议来促进知识收集和交流。我们将与更广泛的国家和国际研究界，包括其他NIBB，通过互动网站和外联活动交流知识和最佳实践，学术科学协会和更广泛的社会。我们设想网络的五个主要产出：1。加强学术机构、IB公司和NIBB之间的互动，建立伙伴关系，将更广泛的研究活动引向消除现有IBBE过程中的瓶颈，开辟新的IBBE机会。确定未来发展基于合成生物学的IBBE工艺所需的有效和高效运输系统所面临的主要挑战。4.通过概念验证资助，支持开发赋能技术。形成多学科团队竞争相关基金要求促进转化研究活动。具有创造力的早期职业科学家，拥有学术界和工业界的联系网络。