Manufacture of complex protein polymers for industry and medicine

Lead Research Organisation: Newcastle University
Department Name: Biosciences Institute

Abstract

Modern biomedical science and clinical medicine rely increasingly upon the growth of cells outside of the body. In this way we can perform animal free experiments which are highly informative about a range of diseases including cancer, arthritis and dementia. We can also use these artificial cell cultures to make new drugs and there is a growing industry making such drugs as Herceptin for cancer and vaccines against hepatitis. Finally we now have the hope of stem cells to create a range of regenerative medicine cures for a range of conditions. In all these cases the cells are growing outside of the body and often require an external scaffolding of molecules to support their normal growth patterns. Currently these scaffolds are every expensive and of limited technical complexity. This project will create a cheap, pure and highly flexible source of polymeric proteins which can be built into a range of products to accelerate and stabilise the growth of cells in culture and assist all the technologies mentioned above.

Technical Summary

Artificial cell culture is a widespread and rapidly expanding technology with applications in medicine, bioprocessing, crop science, drug development and clinical research. Currently, cells grow on surfaces that largely fall into two groups; low cost, bulk materials, exemplified by plastic ware, or high cost, low volume molecules such as proteins or peptide hydrogels. This project seeks to use a recent and patented discovery to create a novel industrial process that will overturn this product landscape by manufacturing engineered protein polymers with advanced functions at low cost. By bridging the gap between traditional polymer science and protein biochemistry we will create a range of matrices to assist the growth of cells for many downstream applications. The five-year project, supported by a broad industrial advisory board will develop a series of prototype materials and production processes and create the foundation for informed private sector investment or public-private partnerships.

Planned Impact

As described in proposal submitted to TSB

Publications

10 25 50
 
Description We have shown that the polymeric protein Caf1 can be used as a biomaterial to support in vitro cell culture in 2D and 3D . We also demonstrated that it can be economically manufactured in an industrially relevant process making it a suitable replacement for a range of materials used for cell culture. We also showed that different forms of Caf1 can be fused together to form mixed polymers with multiple activities.
Exploitation Route We are using a BBSC follow on fund award and the iCURE programme to develop Caf1 into a project suitable for a university spin out. If successful we aim to promote the use of Caf1 in a wide range of cell biology research and cell manufacture
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Formation of spin out company MarraBio to commercialize the Caf1 technology
First Year Of Impact 2022
Sector Manufacturing, including Industrial Biotechology
 
Description Advanced bioactive hydrogels for cell culture and wound care
Amount £31,971 (GBP)
Funding ID NA-CCF 11 (Lakey) 
Organisation United Kingdom Research and Innovation 
Department Northern Accelerator
Sector Charity/Non Profit
Country United Kingdom
Start 03/2019 
End 03/2020
 
Description Developing the Caf1 polymer technology into a commercial proposition
Amount £190,399 (GBP)
Funding ID BB/T017198/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2020 
End 12/2021
 
Description Execs in Business
Amount £30,000 (GBP)
Organisation United Kingdom Research and Innovation 
Department Northern Accelerator
Sector Charity/Non Profit
Country United Kingdom
Start 04/2022 
End 06/2023
 
Description ICURe follow on funding: FY22 round 2 Engineered Protein Polymers for Industrial Cell Culture (EPPICC)
Amount £240,000 (GBP)
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 02/2033 
End 02/2033
 
Description iCURE Cohort 15 "Engineered protein polymers for high performance, multi-purpose biomaterials"
Amount £40,000 (GBP)
Funding ID 35-15 / 520954101 
Organisation Set Squared Partnership 
Sector Private
Start 09/2021 
End 03/2022
 
Description Testing Caf1 effects on osteoprogenitor cells 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution We made Caf1 proteins with BMP2 and osteopontin sequences in them and sent them to Dr Birch in Cambridge
Collaborator Contribution Dr Birch cultured osteoprogenitor cells on our proteins and showed that we could induce bone formation
Impact Peters, D. T., Waller, H., Birch, M. A., and Lakey, J. H. (2019) Engineered mosaic protein polymers; a simple route to multifunctional biomaterials, Journal of Biological Engineering 13, 54.
 
Description Testing induced pluripotent stem cell growth on engineered Caf1 surfaces 
Organisation Cell Therapy Catapult
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Supply of engineered Caf1 coated cell culture plastic and technical advice
Collaborator Contribution Testing our surfaces for the ability to support iPSC culture and expansion. Comparison with existing technology used in the industry. Analysis using measures of cell number, morphology and gene expression profiles Provision of independent report of results with industrial benchmarking
Impact Written report comparing the behaviour of Caf1 variants with current industry standard processes.
Start Year 2020
 
Description Use of Caf1 in models of vascularisation 
Organisation Laboratory for Vascular Translational Science (LVTS)
Country France 
Sector Academic/University 
PI Contribution We supplied Caf1 specifically engineered to promote the growth of endothelial cells in 3D models
Collaborator Contribution They created the methods of creating the 3D models of vacularisation and the methods to analyse the results
Impact Int J Mol Sci . 2022 Nov 23;23(23):14604. doi: 10.3390/ijms232314604. Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior Chau Le Bao 1, Helen Waller 2, Alessandra Dellaquila 1, Daniel Peters 2, Jeremy Lakey 2, Frédéric Chaubet 1, Teresa Simon-Yarza 1 1) LVTS 2) Newcastle
Start Year 2021
 
Description testing caf1 as surface for iPSC cell culture 
Organisation Cell and Gene Therapy Catapult
Country United Kingdom 
Sector Private 
PI Contribution WE will supply engineered Caf1 proteins to test their ability to support hIPSC cell culture
Collaborator Contribution They will compare Caf1 with existing methods
Impact None yet - delayed by COVID lockdown
Start Year 2020
 
Title RECOMBINANT POLYPEPTIDE 
Description The invention provides a chaperone/usher family polymer comprising at least one chaperone/usher family polypeptide monomer, wherein said at least one chaperone/usher family polypeptide monomer comprises an exogenous bioactive sequence. 
IP Reference US2015299272 
Protection Patent granted
Year Protection Granted 2015
Licensed No
Impact Granting of the patent in the USA and Japan is critical to the broad development of the Caf1 polymer material. The grant of the European Patent is expected this year
 
Company Name MARRABIO LIMITED 
Description University spin out to commercialize the Caf1 technology 
Year Established 2022 
Impact None yet as it started trading on 1st Feb 2023
Website http://marrabio.com
 
Description School Visit Ponteland 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact We first visit the school and then later host the children in a practical lab in our institute . The result is a lot of excited kids talking about science and asking loads of questions

School reports a more informed approach to science lessons after they have spent a day doing research
Year(s) Of Engagement Activity Pre-2006,2006,2008,2009,2010,2011,2012,2013,2014