Professor Colin Robinson
Professor in Biotechnology/Head of School
School of Biosciences
- 01227 (82)3443
Professor Colin Robinson joined the School of Biosciences in 2013. He studied Biochemistry as an undergraduate at the University of Edinburgh and went on to carry out a PhD studying chloroplast protein targeting with John Ellis at the University of Warwick. This generated a long-standing interest in protein targeting systems which has remained a dominant interest in the research group. After completing his PhD he spent 2 years at the University of Munich studying mitochondrial protein targeting with Professor Walter Neupert. He then returned to Warwick as a lecturer in 1985 and spent the next 27 years at Warwick as Lecturer, Senior lecturer and finally Professor. His work initially focused on chloroplast protein targeting pathways, particularly those located in thylakoid membranes, but the group’s focus shifted to bacterial systems in more recent years.
Colin is a member of the Industrial Biotechnology and Synthetic Biology Group and the Industrial Biotechnology Cenreback to top
Also view these in the Kent Academic Repository
Understanding and exploiting (i) protein transport systems in bacteria and chloroplasts, and (ii) pathways for high-value products in microalgae
Protein transport systems
Much our research is focused on the mechanisms by which proteins are transported into and across biological membranes. In particular, we are interested in bacterial protein export. Bacteria export numerous proteins into the periplasm (Gram-negative species) or the cell wall/medium (Gram-positives) and the underlying mechanisms have been studied in great detail. Many proteins are exported using the Sec-dependent pathway, in which substrates are 'threaded' through the membrane-bound Sec translocon in an unfolded state. Other proteins are exported by the twin-arginine translocation, or Tat pathway. In this pathway, substrates are synthesised with N-terminal signal peptides containing a key twin-arginine motif. The proteins are then transported by a membrane-bound Tat translocon which is uniquely able to transport fully folded proteins - even oligomeric proteins - across the tightly coupled plasma membrane. Ongoing projects are aimed at understanding how this is achieved, and how the system can be expolited for the production of high-value therapeutic proteins.
Microalgae (which we define here as cyanobacteria and unicellular eukaryotic algae) hold great promise for the biotechnology industry. They divide rapidly, can be grown under phototrophic conditions, and contain a variety of high-value compounds including colourants and oils. However, they also have real potential as cell factories. As part of a large EU-funded consortium, we are developing strains that express pathways for high-value compounds, using the cyanobacterium Synechocystis PCC6803 and the alga Chlamydomonas reinhardtii as host organisms. We are also expressing high-value biotherapeutics in Chlamydomonas in order to assess this organism's potential as a protein production host.
New IB Catalyst project to develop a suite of new tools for production of recombinant proteins in E. coli
Over a third of licensed biopharmaceuticals are produced in Escherichia coli and there is a need to develop new production methods to maintain the UK's competitive edge. The Industrial Biotechnology Catalyst programme is a BBSRC/Innovate UK/EPRSC venture to support larger-scale biotechnology projects in the UK. Prof Colin Robinson is co-ordinator of the project entitled 'A new generation of E. coli expression hosts and tools for recombinant protein production'. This £2.6 million grant funds research at the Universities of Kent, Birmingham and Sheffield. The project also has industrial links with MedImmune, Fuji-Diosynth, Cobra, and UCB.
The primary objective of this project is to develop an integrated E. coli production platform for biopharmaceutical production, incorporating innovations at key stages including product synthesis, folding, export to the periplasm and release to the culture medium. This will provide industry with a powerful alternative to current strategies, most of which are based on decades-old technology. These innovations will have a long-lasting effect on the UK's ability to compete within a market that is currently worth in excess of $100 billion p.a.
The groups involved are as follows:
(WP 1). Production of proteins in a highly regulated manner (Busby group - Birmingham)
(WP 2). Export of proteins from the cytoplasm to the periplasm (Robinson group - Kent)
(WP 3). Characterisation of production strains using advanced proteomics (Wright group - Sheffield)
(WP 4). Release of target proteins from the periplasm (Dafforn group - Birmingham)
(WP 5). Industrial validation (Smales group - Kent)
The bacterial and plant Tat systems - unique mechanism and remarkable 'proofreading' abilites
The unique nature of the Tat mechanism has prompted great interest in the system and we are studying the mechanism (poorly defined so far) the structure of the membrane bound Tat complexes and the 'proofreading' of substrates. Some Tat substrates need to be exported in a properly folded state because they bind complex redox cofactors in the cytoplasm (for example, FeS centres). The system has to be able to 'know' when the substrate is fully folded and with the cofactors in place before it is exported, and recent evidence suggests that this is a complex process. We are using a combination of approaches to dissect the proofreading mechanism and understand this system further.
Exploitation of the Tat system for biotechnological purposes
In BBSRC-funded BRIC and IPA projects, we are working with collaborators at UCL and Oulu (Finland) to develop the Tat system into a biotechnological tool. Many high-value biopharmaceuticals are currently prepared by expression in E. coli and export to the periplasm using the Sec export pathway. Many antibody fragments, for example, are prepared in this manner, and this is now a multi-billion dollar industry. The advantages of this method are: (i) it is easier to purify the target protein from the periplasm and (ii) the periplasm is an oxidising environment - essential for disulphide bond formation. Unfortunately, many heterologous proteins cannot be exported to the periplasm even when a Sec signal peptide is present; this is usually because they fold too quickly, or too tightly, for the Sec system to handle.
The Tat pathway represents a powerful alternative means of exporting proteins to the periplasm. Several studies have shown that heterologous proteins can be exported by attachment of an N-terminal twin-arginine signal peptide, and its ability to export folded proteins means that it may well be able to export a wide range of 'difficult' passenger proteins. Our present studies are aimed at maximising the Tat-dependent export capabilities of the E. coli system and there is now clear evidence that Tat-based export systems have massive potential for the production of recombinat proteins. We have also shown that disulphide-bonded proteins can be exported with high efficiency, especially when expressed in strains that permit the formation of these bonds in the cytoplasm.
New Marie Skłodowska-Curie project, 'ProteinFactory'
The Robinson group is a partner in a newly-awarded MSCA actions Innovative Training Network, 'ProteinFactory'. The project aims to understand and exploit protein export systems in Gram-negative and –positive organisms, in order to develop next-generation secretion platforms. The project involves collaboration withn 9 other research groups and companies throughout Europe, and starts in September 2015.
Synthesis of high-value natural products in microalgae
Many plant natural products are used for therapeutic and other purposes, and one class of products is of particular interest: terpenoids. These are complex plant products, many of which are used by the biotechnology, cosmetic and other industries. There are two key problems: (i) they are usually present in minute quantities in the native plant and (ii) they are almost invariably difficult (often impossible) to synthesise by chemical means. As part of an EU-funded project, 'Photo.comm' we are working with Copenhagen University to express pathways for diterpenoid synthesis in cyanobacteria and Chlamydomonas reinhardtii. The work also involves collaboration with a range of algal experts in the UK, including Saul Purton (UCL) and Alison Smith (Cambridge).
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