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

分子在生物膜上的移动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)过程效率的障碍。出现这种情况的原因是，处理膜蛋白存在明显的困难，转运蛋白的不受控制的表达往往会对细胞产生毒性影响，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以整合到底盘生物体的调节和能量网络中，将是通过促进新工艺的开发来扩大IBBE的经济和社会影响的关键。这个网络的动机是，更深入地了解物质是如何进入、进入和离开细胞工厂的，将导致使能技术的发展，这些技术对几乎所有基于细胞的IBBE应用的未来发展至关重要，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，因为许多概念验证生物生产系统已经建立，但很少有提供商业上可接受的产品浓度，通常是因为所需产品被证明对生产细胞工厂是有毒的。其目标是开发创新的解决方案和技术，以克服现有IBBE过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的IBBE活动的设计中。这次网络竞标的众多优势之一是其重点的交叉性，因此其产出将影响几乎所有基于电池工厂的IBBE过程。因此，我们的网络在与工业生物技术和生物能源(NIBB)以及更广泛的其他网络进行协同互动方面具有独特的地位。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有管理的五年跨学科网络，以促进和交付活动，以培养专注于跨膜传输基材和产品的系统的多学科知识库。这项活动将导致创建具有改进的IBBE能力的使能技术和生物系统。我们设想网络中的四个主要活动水平：1.我们将通过将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，建立协作，并创造创新的解决方案，创建一个有凝聚力的社区。我们将通过一个强大的、有竞争力的概念验证资助计划，支持关注IBBE真正问题的多学科合作研究，该资助计划包括生物、工程和社会科学元素。3.我们将通过参观参与实验室和出席会议来促进知识的收集和交流。我们将通过互动网站和外联活动，与更广泛的国内和国际研究界，包括其他国家和地区研究界，交流知识和最佳做法，学习科学社会和更广泛的社会。我们设想该网络的五项主要成果：1.加强学术机构、IB公司和IBBS之间的互动，以建立伙伴关系，引导更广泛的研究活动，以消除现有IBBE过程中的瓶颈，并打开新的IBBE机会。确定未来发展以合成生物学为基础的IBBE过程需要有效和高效的运输系统所带来的主要挑战。通过概念验证资金支持使能技术的开发。组建多学科团队，在相关资金方面展开竞争，推动翻译研究活动。富有创造力的早期职业科学家，拥有学术界和工业界的人脉网络。

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.