Manufacture of complex protein polymers for industry and medicine
Lead Research Organisation:
Newcastle University
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
Organisations
- Newcastle University (Lead Research Organisation)
- Engineering and Physical Sciences Research Council (Co-funder)
- Cell and Gene Therapy Catapult (Collaboration)
- University of Cambridge (Collaboration)
- Cell Therapy Catapult (Collaboration)
- Laboratory for Vascular Translational Science (LVTS) (Collaboration)
Publications

Akin S
(2017)
Insight into Interface Engineering at TiO 2 /Dye through Molecularly Functionalized Caf1 Biopolymer
in ACS Sustainable Chemistry & Engineering

Al-Jawdah AD
(2019)
Induction of the immunoprotective coat of Yersinia pestis at body temperature is mediated by the Caf1R transcription factor.
in BMC microbiology

Bracchi M
(2019)
The synthesis of poly(arylthiols) and their utilization in the preparation of cross-linked dynamic covalent polymer nanoparticles and hydrogels
in Polymer Chemistry

Dura G
(2022)
Exploiting Meltable Protein Hydrogels to Encapsulate and Culture Cells in 3D.
in Macromolecular bioscience

Dura G
(2021)
Hydrogels of engineered bacterial fimbriae can finely tune 2D human cell culture
in Biomaterials Science

Dura G
(2018)
Tuneable hydrogels of Caf1 protein fibers.
in Materials science & engineering. C, Materials for biological applications

Dura G
(2020)
A Thermally Reformable Protein Polymer
in Chem

Ivanova IG
(2018)
PERK/eIF2a signaling inhibits HIF-induced gene expression during the unfolded protein response via YB1-dependent regulation of HIF1a translation.
in Nucleic acids research

Le Bao C
(2022)
Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior.
in International journal of molecular sciences

Madgwick S
(2022)
Claspin haploinsufficiency leads to defects in fertility, hyperplasia and an increased oncogenic potential.
in The Biochemical journal
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 | 06/2020 |
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 | 03/2022 |
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 | 08/2021 |
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 |