Award details

Metals in Biology: The elements of Biotechnology and Bioenergy

Reference	BB/L013711/1
Principal Investigator / Supervisor	Professor Nigel Robinson
Co-Investigators / Co-Supervisors	Professor Martin Warren
Institution	Durham University
Department	Biosciences
Funding type	Research
Value (£)	325,410
Status	Completed
Type	Research Grant
Start date	20/01/2014
End date	19/01/2018
Duration	48 months

Abstract

The prevalence of metallo-enzymes means that success in synthetic biology may pivot upon an ability to engineer metal-supply inside microorganisms, plants and animal cells. For example, the sustainable manufacture of isobutanol has required the engineering of cellular iron-circuits: Aft1 and Aft2 levels were adjusted to activate genes for iron uptake to provide sufficient metal-cofactor for an introduced dihydroxyacid dehydratase (DHAD) enzyme. The abundance of each metal is controlled inside cells by sensors (such as Aft1 and Aft2) that regulate metal import, metal export, metal trafficking and metal storage systems, they also switch metabolism to take advantage of more available metals and to minimise demand for those in deficiency. Metals which form tight complexes with proteins are held at low abundance while weaker binding metals are maintained at concentrations many millions of times higher. Under these controlled conditions the metallo-enzymes acquire the correct metals. Network members will work with the bio-processing sector to optimise metal availability inside cells to give consistent biologic quality and yield. They will develop antimicrobial-chelants, ionophores and metal nano-particles that subvert the metal-handling systems of micro-organisms, they will explore the impact of microbes on the mobility of metal contaminants in the environment and engineer metal bio-accumulation and bio-detection. Members will collaborate with multiple companies to engineer synthetic metallo-enzymes and will optimise metal uptake and assimilation into biomolecules required for bio-energy production, bioremediation, biomedicine and synthesis of high value industrial feed-stocks. This network will consolidate the activities of communities working on Metals in Biology and speed the exploitation of those aspects of their research relevant to industrial biotechnology and bioenergy.

Summary

The purpose of this network is to make the UK the premier destination for research and development that demands Metals in Biology expertise. Metals catalyse the reactions of life and these demands are expected to grow. Some of the earliest discoveries, uncovering metals as vital components of proteins and not mere contaminants, were made in the UK. Today we have world leaders uncovering how cells handle metals and the mechanisms of metal-dependent enzymes. Now is an opportune moment to exploit this knowledge to the benefit of industry and society. UK businesses which will innovate with this knowledge include established world leaders in their sectors and new entrants. Metallo-proteins contribute to bio-energy production, bioremediation, biomedicine, synthesis of high value industrial feed-stocks and more. The metal-handling systems of cells are vital to sustain adequate metal-protein speciation in vivo. As nearly a half of enzymes, perhaps one third of all gene products, are estimated to require metals, the impact of this network will be pervasive. Metal-handling circuits can also be subverted to inhibit microbes. The exploitation of metals and metal-chelators as antimicrobials is a form of bio-mimicry since we are now starting to discover that immune systems manipulate metal-supply to inhibit microbial growth. Indeed, many common antibiotics tightly bind to metals and some antibiotics are closely related to iron-scavenging molecules (siderophores). Metal-supply pathways can be engineered for the manufacture of supplements such as cobalt-requiring vitamin B12 and enzymes with metallo-prosthetic groups. Talented individuals are currently scattered in different UK research communities. The efforts of biologists, chemists, mathematicians, engineers and others will be drawn together by this network to allow effective knowledge and skills transfer with industry and with the relevant regulatory authorities. The network will run for three years with structured workshops, a large community building meeting and additional ad hoc workshops throughout the tenure of the network.

Impact Summary

The network will have diverse impacts due to the pervasive nature of metals in biology (refer to case for support). Contributions to Industrial Biotechnology and Bioenergy can be categorised under the following headings: Metals in bio-processing Metal-related antimicrobials Metal circuits for synthetic biology, bio-energy and industrial biotechnology Metals in the environment Metal-related nutrition and supplements Metallo-enzyme engineering for bio-energy and industrial biotechnology Tools and technologies for metals in biology A purpose of this network is to promote interactions between the Metals in Biology research community and non-academic beneficiaries. We already have over 100 members and yet consider that a major role for the network will be to disseminate awareness of the significance of the sub-discipline and the opportunities that it presents, most especially outside the confines of academia. We intend to grow these numbers especially from industry. The names on the members' lists provide an early indication of some of the many beneficiaries, in academia and also within industry, regulatory and advisory bodies. Most of these individuals approached the network to request membership and all have been re-contacted in the closing week before submision of this proposal to ensure that they wish to be on these lists (this efficiency has avoided innumerable letters of support). Throughout the term of the award, and in response to enquiries for expertise (from BBSRC, industry, government, outreach organisations and others) the network manager will liaise with the membership to source the best individuals to provide advice. The PI and CoI are actively involved in outreach activities including the generation of press releases, and the CoI has written popular science books and contributed to BBC TV series. Throughout the network such best practice will be disseminated within this community. The network manager and clerical assistant will deliver communications and promote the network, support members, maintain databases, gather information, assemble reports and brochures throughout the term of the award (see work-plan). The network manager is already part of a business engagement team so will bring contacts and sector knowledge into this role. The research emanating from funded projects will be published in open access high impact journals and oral communications given at international conferences (after adequate protection of IP where needed). The track records of the PI, CoI and management team, attest to their commitment to such forms of impact activities. Knowledge and skills acquired as a result of network activities (by PI's and also by RAs linked to funded projects) will be applicable to a broad swathe of academia and industry. Crucially, the intellectual property (IP) resulting from the projects associated with the network will be protected via company/institutional innovation and enterprise offices. The network will foster rapid routes to exploitation of such IP.

Committee	Research Committee D (Molecules, cells and industrial biotechnology)
Research Topics	Industrial Biotechnology, Microbiology, Synthetic Biology
Research Priority	X – Research Priority information not available
Research Initiative	Networks in Industrial Biotechnology and Bioenergy (NIBB) [2013]
Funding Scheme	X – not Funded via a specific Funding Scheme

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