Modelling recombinant protein folding and secretion (ITN “SECRETERS”)
euraxess
United Kingdom
16d ago

The SECRETERS ITN project aims to develop A new generation of microbial expression hosts and tools for the production of biotherapeutics and high-value enzymes .

A new generation of microbial expression hosts and tools for the production of biotherapeutics and high-value enzymes

The appointed ESR will work within the SECRETERS Innovative Training Network (ITN), building on a decade of experience in the host group with modelling the dynamics of protein synthesis in recombinant protein expression systems.

The aim of the project is to develop computational models of redox-related processes in Escherichia coli and Pichia pastoris.

Modelling will be informed by results from other, experimental projects in this network, and the project will act as a hub that brings together results from a large number of other approaches.

Specific aims will include predicting the maximum capacity of host cells to process recombinant proteins, predicting the magnitude of response of endogenous stress pathways, and identifying bottlenecks that would be useful starting points for strain improvement strategies.

Candidates for this project should have a background in molecular biology with a working knowledge of computational modelling or bioinformatics, OR a background in computing with a working knowledge of molecular biology.

Existing publications upon which this project is based include :

Khan et al. (2018) Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2. J Theor Biol 445 : 92-102.

Chu et al. (2014) Translation elongation can control translation initiation on eukaryotic mRNAs. EMBO J 33 : 21-34.

The ESR will participate in an extensive training programme, including secondments to industrial partners in the consortium.

The contract will be for 3 years and the ESR will be registered as a PhD student at the University of Groningen.

The SECRETERS’ partnership will involve collaborations between 6 academic and 5 industrial participants, who are based in 6 European countries.

The objective is to bring about a step change in the production of recombinant proteins, particularly Biotherapeutics and Industrial Enzymes.

Both are critical products for the EU biotechnology sector, with combined markets in excess of $140 billion p.a.; the former are essential for the treatment of major diseases whereas the latter permeate every aspect of our daily life.

Many proteins in these categories pose severe problems in production, especially disulphide-bonded proteins and new format 'difficult-

to-express' proteins. SECRETERS will train a team of 15 ESRs to develop a new generation of super-producing microbial production hosts, including Escherichia coli, Bacillus species and the yeast Pichia pastoris.

The project capitalises on a series of recent innovations and involves close collaboration between 6 academic Beneficiaries, who provide world-

leading expertise in redox chemistry, synthetic biology and protein expression, and 5 non-academic Beneficiaries, who include some of the world's premier biotherapeutic and industrial enzyme companies.

It will enable the biotherapeutics industry to produce challenging medicines at lower costs, resulting in new drugs and wider patient access, and allow the enzymes industry to deliver a range of powerful new products.

Based on a responsible innovation approach, with clear foci on research and entrepreneurial training, SECRETERS will deliver a team of superbly-

trained scientists, poised to engage in some of Europe's most important biotechnology sectors.

Escherichia coli

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