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

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.

Moving molecules across membranes is a barrier to improving many existing Industrial Biotechnology and Bio-Energy (IBBE) processes that utilize cell factories. With the advent of synthetic biology, identifying transport systems for integration into chassis organisms will be crucial in expanding the economic and social impacts of IBBE. The motivation for this network is that understanding the mechanisms by which 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. The proposal is timely because many laboratory-scale systems have been established, but few provide commercially acceptable product yields. 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 consideration of transport systems in future IBBE activities. One the many strengths of this proposal is the cross-cutting nature of its focus, such that its outputs will impact on almost all cell-factory-based IBBE processes. Thus we are uniquely positioned to synergistically interact with other Networks in Industrial Biotechnology and Bioenergy (NIBB), as well as more widely.

In a managed five-year network of academics, industrial partners and other stakeholders we will:

1. Create a cohesive community of experts from different disciplines to share knowledge, identify key questions/bottlenecks, forge collaborations and create innovative solutions.
2. Support multi-disciplinary, collaborative research through a robust, competitive Proof-of-Concept funding program that includes biological, engineering and social scientific elements.
3. Promote knowledge gathering and exchange.
4. Engage with the broader research community, including other NIBBs, learned scientific societies and the public via an interactive website and outreach events.

IBBE is one of the three BBSRC strategic research priorities and will be a major contributor to the UK economy in the 21st century. The proposed network will identify new opportunities to improve existing IBBE processes by overcoming barriers imposed by inefficient transport of substrates and products. By creating innovative solutions and supporting multi-disciplinary institutional-industry collaborations the network activities will translate biological knowledge into bio-industrial know-how leading to new opportunities founded on improved process efficiencies. A major impact of the network will be improved community interactions between academic and the IBBE business sector through the coordination of activities and better communication channels to direct research activity to real IBBE sector needs. These activities will build capacity and lead to partnerships that will enhance the ability of the UK to maximize translation of its strengths in fundamental research. To establish the UK as an internationally recognized partner of choice in the IBBE sector requires a highly-trained inter-disciplinary workforce operating able to service the needs of industry. This network will form a cohesive community deploying the latest systems and synthetic biology approaches to enhance UK competitiveness as a place to do business in the IBBE sector. IBBE activities often involve the application of what might be considered controversial science - engaging with the public is an important network activity because a better informed population will be better placed to influence policy-makers.