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

在生物膜上移动分子是提高许多现有的利用细胞工厂的工业生物技术和生物能源（IBBE）工艺效率的一个障碍。这样做的原因是与膜蛋白一起工作的困难，以及不受控制的转运蛋白表达的细胞毒性作用，以及与产物积累相关的毒性。此外，随着合成生物学的出现，通过促进新过程的发展，确定适当的运输系统以整合到底盘生物体的调节和能量网络中，对于扩大IBBE的经济和社会影响至关重要。建立这一网络的动机是，对物质如何进入、进入和离开细胞工厂有了更深入的了解，这将导致对几乎所有基于细胞的IBBE应用的未来发展至关重要的技术的发展，包括自下而上的系统设计（合成生物学）。这一网络建议是及时的，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，通常是因为所需的产品被证明对生产细胞工厂有毒。目标是开发创新的解决方案和技术，以克服现有IBBE流程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。该网络投标的众多优势之一是其重点的交叉性质，因此其输出将影响几乎所有基于细胞工厂的IBBE过程。因此，我们的网络具有独特的定位，可以与工业生物技术和生物能源（NIBB）的其他网络以及更广泛的网络协同互动。为了实现我们的目标，我们建议组建一个由学术界、工业合作伙伴和其他利益相关者组成的管理五年的跨学科网络，以促进和交付事件，以培养一个多学科的知识库，重点关注跨膜运输底物和产品的系统。这项活动将导致创造具有改进IBBE能力的使能技术和生物系统。我们设想在网络内开展四个主要层次的活动：我们将创建一个有凝聚力的社区，将来自不同相关学科的专家聚集在一起，分享知识，确定关键问题/瓶颈，建立合作并创造创新的解决方案。我们将通过一个强有力的、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，支持多学科的、专注于“真正的”IBBE问题的合作研究。3. 我们将通过参观参与的实验室和参加会议来促进知识的收集和交流。我们将通过互动网站和外展活动，与包括其他nibs在内的更广泛的国内和国际研究界、学术科学团体和更广泛的社会交流知识和最佳实践。我们设想该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，引导更广泛的研究活动，消除现有IBBE流程中的瓶颈，并开辟新的IBBE机会。2 .确定未来基于合成生物学的IBBE工艺发展需要有效和高效的运输系统所面临的主要挑战。3 .通过概念验证资金支持实现技术的开发。组建多学科团队，在相关的资助项目中竞争，促进转化研究活动。有创造力的早期职业科学家，在学术界和工业界都有联系。

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.