The University of Manchester - Proximity to Discovery: Industry Engagement Fund - Phase 4

Lead Research Organisation: University of Manchester

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The MRC Proximity to Discovery scheme awards universities funds to help develop new collaborations, and ways of exchanging knowledge and skills. The awards can be used to support activities that promote the value of academic-industry partnership, and enhance academic and industry researchers’ understanding of each other’s needs and capabilities. This may be through people exchanges, creation of technology demonstrators, showcase events, commercialisation workshops and ‘entrepreneurs in residence’ schemes. Such exchanges of knowledge and skills will boost the most fruitful collaborations between UK universities and life science companies.

Publications

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Description Assessing cutaneous lipidomic changes associated with novel RNA delivery vectors 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution This collaboration is intended to be proof of principal work to explore how combining lipidomic (University of Manchester) and mass spectrometry imaging (AstraZeneca) can forge an alliance for the future development of delivery vector safety and efficacy models. Lipid nanoparticles (LNPs) are currently the gold standard for subcutaneous therapeutic RNA delivery. An understanding of the interaction of these materials with the local skin environment is key for AstraZeneca (AZ) as new RNA therapies are developed, and of particular interest is how LNPs react with the cutaneous lipidome and how this might affect the tolerability of delivered LNPs. While AZ have not established the technologies to investigate this, skin lipidomic research at the University of Manchester (UoM) is well advanced, therefore collaboration with the University is essential. Furthermore, AZ have access to world leading mass spec imaging technologies that could be developed to better assess the localisation of LNPs. Secondments by scientists from UoM and AZ to the partners' labs will leverage knowledge transfer and facilitate use of global and in situ lipidomics to profile skin distribution of LNPs and associated changes in the lipidome and to support development of better delivery vectors for efficacious RNA based medicines. The work proposed for this project will be key to understanding the associated toxicities of these vectors, with the prospect for the development of both new and improved delivery systems and new and improved medicines to benefit both AZ's drug development pipeline and more importantly the health of recipient patients. To investigate how changes to skin lipidome can contribute to LNP-induced inflammation, the project will use delivery of LNPs to 3D skin models and assess global and in situ changes, applying global quantitative lipidomics and mass spectrometry imaging. The study will reveal the perturbation of the lipidome and formation of pro-inflammatory lipids, and show the LNP distribution within the skin. Furthermore, the project will explore how well these changes translate to animal models, using in vivo rodent skin delivery and comparing the results to the in vitro work. A successful outcome will be to find what lipid changes are associated with LNP delivery and how different LNPs can affect change. This has not previously been investigated, will be highly publishable, attract funding, and bring significant benefit to AstraZeneca's RNA therapeutic pipeline.
Collaborator Contribution As above
Impact None as yet, project ongoing
Start Year 2018
 
Description The Bio in the Gel: Bioprinting of novel peptide-based hydrogels and IPSC cells for Articular Cartilage (AC) 
Organisation Biogelx
Country United Kingdom 
Sector Private 
PI Contribution This projects aims to develop novel bioinks for 3D bioprinting of cell-laden constructs, with tailored physicochemical properties that mimic the extracellular matrix (ECM) microenvironment, and instruct induced Pluripotent Stem Cell (iPSC) differentiation towards the regeneration of AC tissue. Stage 1- Hydrogel development for 3D iPSC cell culture (Months 1-5): Dr. Cristopher Allan (CA) will spend 15 days at UoM working with the PI/Co-I to evaluate the in vitro viability and chondrogenic differentiation of iPSC cells encapsulated in the Biogelx hydrogels. The PI/PDRA will spend 10 days with CA at Biogelx and use obtained results to refine hydrogel's properties (e.g. stiffness) and enhance chondrogenic differentiation with thiofunctional chondroitin, laminin and collagen mimetic peptide sequences. Stage 2- 3D bioprinting of novel iPSC cell-laden bioinks (Months 5-9): Optimized hydrogels (Task 1) will be used to bioprint 3D iPSC cell-laden models for AC regeneration. At UoM, the PI/Co-I will provide access to state of the art 3D bioprinting and cell culture facilities where CA will be trained and gain a better understanding of the biological/printing requirements associated with the synthesis of bioinks. The PI/PDRA will then spend 15 days at Biogelx where CA will inform on hydrogel optimization and Quality Insurance requirements associated with the development/commercialisation of bioinks. Stage 3 - Dissemination/Business Engagement Workshops (Month 9): Organized by the PI/Co-I/Biogelx through the Royce Institute and MaRM to disseminate project outputs and discuss new strategies for effective engagement between UoM academics and Industry.
Collaborator Contribution Biogelx offers patented 3D peptide hydrogels that can be chemically and mechanically modified providing a flexible platform to recreate various tissue environments and influence cell growth. The proposed project would support the R&D required for developing novel hydrogel products in these areas. The company's current commercial offerings have been possible through researchers working in an interdisciplinary manner between chemistry and cell biology. This project is an opportunity to exchange knowledge in a similar manner, targeting optimal gel design for Bioprinting of skeletal tissue models. Biogelx would seek to add any newly developed hydrogel formulations/bioinks from this project, to its current product line, through potentially licensing any background IP required from the University. The technology developed also has the potential to translate into other high value markets such as drug development by allowing the generation of more physiologically-relevant and predictive in vitro models, thus strengthening Biogelx's commercial position in such markets.
Impact N/A, still active
Start Year 2018