The University of Manchester - Proximity to Discovery: Industry Engagement Fund - Phase 4
Lead Research Organisation:
University of Manchester
Department Name: UNLISTED
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.
People |
ORCID iD |
Publications
Robbins J
(2020)
PO-1650: Evaluating plan robustness for organ deformation and set-up uncertainties in head and neck cancer
in Radiotherapy and Oncology
| Description | University of Manchester Intellectual Property PoP Award (for 'A commercial consultation and feasibility study for patient immune responses to anti-TNF biological medicines') |
| Amount | £98,950 (GBP) |
| Organisation | University of Manchester |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | |
| Title | The Bio in the Gel: Bioprinting of novel peptide-based hydrogels and IPSC cells for Articular Cartilage (AC) |
| Description | A detailed SOP for the bioprinting of cellular and acellular constructs using extrusion based systems was established and transferred to Biogelx. This can now be used as guideline for the printing of Biogelx commercial bioinks. |
| Type Of Material | Biological samples |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | TBC |
| Title | Developing Actionable Free-Text from electronic health records for Clinical Decision Support (DAFT-CDS) |
| Description | A large labelled EHR dataset will be an output from this project |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | TBC |
| 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 | We have successfully used targeted and untargeted lipidomics and MSI to analyse mouse skin and validated the use of these technologies using a complex biological tissue. A small pilot study using mouse skin biopsies was performed to permit optimisation of the extraction and analysis protocols for targeted and untargeted lipidomics. The main extended study included groups of mice injected with LNPs and sacrificed at different time points. Importantly, the same skin sections were analysed by UPLC/ESI-MS/MS, UPC2-QToF MS and MSI, allowing for the direct comparison of different technological approaches. This allowed us to compare the performance of various mass spectrometry techniques. In this project, we were also able to evaluate changes in the cutaneous lipidome at the site of injection and away from it, and study temporal changes in the skin lipid mediators after delivering LNPs. We were also able to compare the MSI generated images to skin histology (H&E) ones, and in this way appraise the value of MSI applications. Dr Camacho-Munoz, PDRA employed to work on the project, and Ms A Basak, PhD student at Manchester, spent time at AstraZeneca receiving training on sample preparation and the use of MSI. Dr Gregory Hamm (AZ) spent time at the University learning about skin lipidomics. Dr Mick Fellows (AZ) visited the University for discussions. The project team communicated via skype on a monthly basis. The only issue we encountered was shortage on human skin availability but this allowed us to spend more time in performing a comprehensive study with mouse skin that produced publication quality data. The Academic has had access to MSI technologies that would otherwise have been too expensive and difficult to obtain. We have been able to explore a range of new technologies and their potential benefits to our research without incurring huge costs and with ongoing support from AstraZeneca. The PDRA spent time in AstraZeneca laboratories in Cambridge, observing the analytical work they do using MSI analysis. This involved sample preparation, MSI analysis and data analysis. A UoM PhD student also benefited from this training and had the opportunity to perform experiments using human keratinocytes grown on slides and analysed by MSI. This work was not part of the initial plan but, with the support of AZ, we were able to explore another application that will now be developed as part of the student's PhD work. Furthermore, we obtained new information on mouse skin lipids that will inform future work and provide a better understand the role of lipids in skin inflammation. The data from this project will be reported in a manuscript (in preparation) that will be submitted to a high impact dermatology journal (target journals are the Journal of the American Medical Association: Dermatology or The Journal of Investigative Dermatology). We will continue to benefit from the strengthened relationship with AstraZeneca. Our regular meetings with the company partner and secondments have provided invaluable feedback on the priorities of each partner, leveraged knowledge transfer and facilitated the use of global and in situ lipidomics to profile skin distribution of LNPs and associated changes in the lipidome. The work has highlighted previously unknown lipidomic markers of LNP induced inflammation. Furthermore, the work is helping to validate how mass spec imaging combined with lipidomic analysis can be used to assess potential skin toxicities. |
| Start Year | 2018 |
| Description | Bringing Probabilistic Planning to Clinic |
| Organisation | RaySearch Laboratories |
| Country | Sweden |
| Sector | Private |
| PI Contribution | Funds were provided for a software developer for 2 months. The company provided £1,760 of in-kind support in the form of technical support. |
| Collaborator Contribution | Treating cancer with radiation is a balancing act between giving enough radiation dose to the tumour(s) and sparing healthy organs nearby. Currently, a large region around the tumour is treated with a high dose to account for uncertainties of tumour spread and motion during treatment. With probabilistic treatment planning (PTP), this region is reduced by allowing the optimization process to account for the uncertainties directly, thereby reducing harmful dose to organs nearby. PTP has not been implemented into the clinic as it is computationally very demanding; taking an unacceptable length of time per time. RaySearch, the industry partner, has developed a treatment planning system, RayStation, which is considerably faster than other systems available. This feasibility project aims to integrate our research PTP code within the company's system. A software developer from the University and engineering expertise from the company will work collaboratively to implement an interface to integrate our research code to be used within RayStation's optimization process. RaySearch will provide us with in-depth technical support throughout the project, which is invaluable in making the project a success. Once functional, the application will be used to perform planning studies comparing PTV-based treatments to probabilistic treatments using published geometrical uncertainties for pancreas cancer patients. This pilot project will test and validate the implementation and revise wherever it is necessary. After proving feasibility it is hoped that the collaborators will deliver a joint clinical trial, with a line of sight to future commercialisation of PTP as a module of RayStation. |
| Impact | Project ongoing (start date 15th November 2018, end date 14th March 2019) |
| Start Year | 2018 |
| Description | Clinical assessment and validation of mucus biomarkers of disease activity in Inflammatory Bowel Disease (IBD) |
| Organisation | Origin Sciences Limited |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | IBDs are serious chronic conditions of the gut that remit and relapse and have a major impact on quality of life. They require long term medication, a common need for surgery and have an increased risk of colonic malignancy. Clinical biomarkers like faecal calprotectin have some utility in diagnosis of IBD but cannot accurately predict relapse of IBD patients. There is an unmet need in assessing disease activity and targeting appropriate therapies to patients. The aim of this project is to validate a novel set of biomarkers for IBD as the first step towards developing a diagnostic/prognostic platform for the care/management of IBD patients. There is interest in profiling gut bacteria and host proteins to understand disease risk, as data has shown that gut mucus covering host cells contains microbial communities that are a more sensitive predictor of colitis than faecal microbes. Origin has developed the OriCol™ device, which collects a rectal mucus sample which, in combination with our machine learning approaches to analyse gut bacteria and validated protocols to investigate host proteins, provides a route to deliver an assay with improved clinical utility. The PDRA will spend time based at the company to learn about their priorities, share protocols and samples, and conduct focused analysis using machine learning on the archive microbial data alongside analysis of host proteins. Further analysis of the samples will increase the power of initial finding and provide the evidence base for future collaborative funding application. Preliminary analysis will look at possible linkage of host proteins and microbial species and profiling of focused mucus metabolites. During the project both partners will draft a joint application to further work to investigate markers in IBD, as well as consider potential in other diseases areas of interest to the company, such as cancer. Numerous academics at the University have been working on overlapping projects to define mucus microbes and metabolites in IBD and develop systematic ways to interrogate the data. By working with Origin we can investigate translational into human disease and commercial this knowledge. |
| Collaborator Contribution | as above |
| Impact | We have a shared understanding of our ways of working and have shared protocols and data sets. We have demonstrated the need for optimising sample retrieval and buffer selection We have identified that human mucus and faecal microbes are distinct and identified microbes for follow on study and developed a cell culture system that will enable us to do this. We have plans to collaborate on a further grant proposal We have shared microbiome data to allow independent analysis by Manchester using their analysis pipeline We have shared protocols and our approach for buffer work up to facilitate future sample analysis in Manchester The analysis of the microbiome and mucus metabolites has shown the importance of defining experimental systems e.g. mouse cage and maternal source. This has led to work submitting a grant to NC3R to better define and refine animal experimental models for microbiome analysis (CK, SC). There are plans to submit a grant with Origin in order to assess the mucus and rectal microbiome in patient samples. There are plans to submit a grant with Origin in order to assess the mucus and rectal microbiome in patient samples. |
| Start Year | 2018 |
| Description | Studying the response of wounds to dressings using a collagen model of diabetic foot infection |
| Organisation | Systagenix Wound Management Manufacturing |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | There is an unmet need in the wound care industry for models of diabetic foot infection, and soft tissue infection more generally, that give meaningful data for assessment of wound dressings in terms of anti-biofilm activity, toxicity, healing and protease reduction. A collagen based model of biofilm infection in a wound has been developed to assess anti-biofilm activity of a void filling device, and since publication the model has been developed to include human cells. The project aims to use wound dressings from Systagenix to develop new capabilities of the wound model so that can be used to give meaningful data for assessment of wound dressings as listed above, and to gain an understanding of what the wound care field needs a model to be able to demonstrate. The project will also foster understanding within the academic group on the areas of interest to industry and for Systagenix to learn more about the facilities and opportunities available at the University of Manchester, as it is hoped that the model will provide the potential for a greater range of wound care testing in the future and generate data for publication and IP for licencing of the model. The teams at Systagenix and the University of Manchester will visit the laboratories and manufacturing facilities of the new collagen dressing pilot plant to increase product awareness and to look at cell viability in the presence of wound dressings with and without actives. The cell viability assay will be adapted during the course of the project, and the impact of wound dressings on proteases will be assessed. Along with the usual benefits of collaboration with a new industrial partner, this project allows the academic to develop a translational model with feedback at each stage from industry, to ensure the model is designed according to industry requirements. |
| Collaborator Contribution | as above |
| Impact | none as yet |
| Start Year | 2019 |
| 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 | From this collaborative research project the following benefits were also achieved by our team: - A new set of hydrogels with tuneable physicochemical properties were developed and can be used by our group and others at UoM for the printing of reproducible 3D constructs capable of matching the properties of native AC. - Preliminary results confirm the potential of these materials for applications that go beyond AC regeneration, in particular due to the easy tuneability of their physical properties. Further work will be required in terms of functionalization and compatibility with commercial live/dead assays in order to be used by other groups as reproducible tissue models in areas that span from neurovascular to skeletal tissue engineering. - Through the exchange of academic staff with BiogelX we have gained a new set of skills that allow us to better understand how the physicochemical properties of the materials can be tuned to elicit specific cellular responses. We have also benefited from the vast experience of BiogelX on the rheological characterization of materials to improve the printability of our materials without compromising cellular function. - Benefiting from the Biogelx market intelligence to develop industrially driven solutions we are now much more aware of the steps required take our research products from the bench to the bed side. - The work was already presented at scientific conferences and an international journal publication is being considered. However, further experiments will be required to validate some of the preliminary results. This industry secondment project has greatly benefited BiogelX at different levels including: - Advanced training of technical staff on the biological evaluation of cell laden hydrogels and 3D Bioprinting of bioinks using extrusion-based systems. This new set of skills and knowledge will enable BiogelX to further optimize their materials as well as to develop novel systems with enhanced bioactivity whilst ensuring easy printability. - A new set of bioinks with different chemical formulations can now be supplied to BiogelX customers along with a SOP for 3D printing of tissue engineered constructs. This will expand the range of commercial products being offered by BiogelX, bring economic benefits and consolidate their position in a very competitive market. - The establishment of a strong collaboration with two groups at UoM in the fields of stem cells and bioprinting that will open opportunities for future funding applications targeting the development of tissue engineered products. Our group and BiogelX will continue working together beyond the end date of this project with the aim of refining/optimizing the biological performance of the developed bioinks, particularly for AC regeneration. As stated in the initial project application we will seek further financial support through the following routes: - An MRC Confidence in Concept grant application (with Biogelx) aiming at the 3D bioprinting of Articular Cartilage iPSC tissue models with biomimetic zonal organization (superficial, middle and deep zones) will be developed. - A Future Leader fellowship is currently being prepared by the PI for submission in October 2020 and will include BiogelX as a collaborator on the development of bioinks for 3D tissue models. - An EPSRC responsive mode grant is being prepared by the Pi and Co-I for submission in 2020 and will include BiogelX as industrial collaborator. This will be a follow on of the current project aiming at the development of AC tissue models |
| Start Year | 2018 |
| Description | Attendance at BioProNet 10/11th Oct 2018 (A commercial consultation and feasibility study for patient immune responses to anti-TNF biological medicines) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Outreach & awareness |
| Year(s) Of Engagement Activity | 2018 |
| Description | Bringing probabilistic planning to clinic - 2 papers in Conference Proceedings at 19th International Conference on the use of Computers in Radiation Therapy |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Short paper (2-pages) in conference proceedings: 1- Modelling the effect of time varying organ deformations in head and neck cancer using a PCA model. Jennifer Robbins. http://iccr-mcma.org/ICCR_MCMA_AbstractDocs.pdf Short paper already online 2- Contour Generation with Realistic Inter-observer Variation. Eliana Vasquez Osorio. http://iccr-mcma.org/ICCR_MCMA_AbstractDocs.pdf Short paper already online |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://iccr-mcma.org/ICCR_MCMA_AbstractDocs.pdf |
| Description | The Bio in the Gel: Bioprinting of novel peptide-based hydrogels and IPSC cells for Articular Cartilage (AC) - PI presentation at Science Festival / Pint of Science |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Engaged with local audience to bring science in an understandable and relatable manner |
| Year(s) Of Engagement Activity | 2019 |