£1.2M awarded through inaugural Partnerships and impact funding call

Pablo’s award will build on the foundations of his NC3Rs infrastructure grant to demonstrate the broader applicability of human lymphoid organoid and lymphoid tissue precision cut explant models developed in his lab. He will further characterise the cellular and biochemical profiles of the models using single-cell RNA sequencing, high-dimensional flow cytometry and high content microscopy to generate an open database of multimodal datasets for other researchers to use. Pablo will also partner with four new end-user labs at the Universities of Dundee, Oxford and Muenster to test the transferability and portability of the organoid and explant models – through these collaborations the models will be applied to study key immunological processes, including B-cell germinal centre reactions, antibacterial immune response and T-cell activation and generation, replacing the need for mouse models. 

Kate’s award will build further confidence in a refined oral glucose tolerance test protocol for mice, previously supported by NC3Rs funding, in which a micropipette-guided approach enables the glucose solution to be administered without the need for oral gavage or intraperitoneal injection. The refined protocol still requires the mice to initially be restrained by scruffing to habituate to the dosing procedure and with this award, Kate will partner with Professor Emma Robinson at the University of Bristol to incorporate handling-free techniques into the protocols. Following optimisation, the award will support Kate to partner with six leading institutes based in the UK, USA, Denmark and New Zealand to enable the independent qualification of the protocols within the wider metabolic research field and in different experimental contexts, including for type-2 and pregnancy-associated diabetes. Kate will also develop detailed standard operating protocols, training videos and online materials to facilitate adoption by other groups. Roll-out of the refined protocol to Kate’s partner labs will benefit at least 800 mice annually.

Catarina’s award will facilitate the use of Direct RNAi-Fragment Sequencing (DRiF-Seq) technology, a cutting-edge genetic tool developed with an NC3Rs Project grant, for the study of African trypanosomes – insect-borne parasites that cause deadly infections in humans and cattle. Traditional genetic methods used to assess parasite infection, survival, transmission and drug resistance typically require the use of large numbers of mice as only one mutant can be tested per animal, whereas the DRiF-Seq technology allows for the high-throughput phenotyping of more than 5,000 trypanosome mutants simultaneously within a single animal. During the project Catarina will provide hands-on training in the DRiF-Seq methods (including mutant library production, processing, sequencing and analysis of datasets) to four leading trypanosome research labs based in the UK, Portugal and the Czech Republic. The collaborating labs will apply the technology to study fundamental trypanosome biology including functional genetic studies, investigate parasite drug resistance and identify new therapeutics, reducing the use of approximately 8,000 mice. Catarina will also create comprehensive protocols to allow for independent and wider adoption of these methods.

Richard’s project, in collaboration with the biotechnology company Fluid Pharma, will facilitate the adoption of a palatable tamoxifen diet at the Cancer Research UK Cambridge Institute. Tamoxifen is commonly used to control spatial and temporal gene expression in studies using transgenic mice. Rodent diet containing tamoxifen is commercially available, but its bitter taste means that it is not readily consumed by mice and this can lead to weight loss as well inter-animal variability in the data obtained and subsequent issues with reproducibility of the studies. Consequently, tamoxifen is often administered by oral gavage or by subcutaneous or intraperitoneal injection. With previous NC3Rs CRACK IT funding, Fluid Pharma have developed micropellets layered with tamoxifen and encapsulated in a taste-masking coating that allows the drug to be added to the rodent diet without changing its palatability. Collaborators at The Mary Lyon Centre at MRC Harwell have worked closely with Fluid Pharma to assess food intake and the dose efficiency of the tasteless tamoxifen diet, demonstrating the welfare and scientific benefits of this innovative product. The award to Richard, the core facility manager at the Cancer Research UK Cambridge Institute, will now enable labs at the Institute to use the diet, helping to build confidence in the utility of this alternative approach for administering tamoxifen. Implementation of the refinement at the Institute will directly benefit more than 4,000 mice over the next three years.

Sarah’s award will enable the transfer two in vitro endothelialised thrombosis models, originally developed with an NC3Rs-BHF studentships award, to two labs where they will be optimised and tested for their fit-for-purpose in platelet and stroke research. Mouse models of thrombosis are widely used but lack standardisation, have limited human relevance and often use large numbers of animals to detect biologically relevant effects. Sarah will partner with researchers at the University of Reading to transfer her in vitro endothelialised model, designed to measure endothelial contributions to thrombus formation and antithrombotic efficacy, so that it can be adapted to incorporate a different fluidic system commonly used in the platelet research field. She will also collaborate with researchers at the University of Manchester to transfer her complex in vitro model of ferric chloride thrombosis to replace some mouse studies of ferric chloride-induced middle cerebral artery occlusion in the testing of thrombolytics.

Manuel’s award will support the transfer of the engineered vascular tissue model developed during his joint BHF-NC3Rs PhD studentship to the lab of Professor Sanjay Sinha at the University of Cambridge for use in the study of aortic aneurysmal disease. The project will expand the applicability of the model by incorporating induced pluripotent stem cell-derived human vascular smooth muscle cells with defined mutations of aortic and vascular diseases, a technology pioneered by the Sinha lab and used to study genetic predispositions to vascular disease. The suitability of the model for replacing the use of mice in the Sinha lab for investigating mechanistic links between specific mutations and aneurysm formation will be evaluated using proteomic analyses of the extracellular matrix and benchmarking studies against human aneurysmal tissue samples. 

Helen’s award will enable her team to adopt the 3D humanised self-structuring in vitro bone model developed in Dr Amy Naylor’s lab at the University of Birmingham, with an NC3Rs PhD studentship where it will be used to replace mouse models for some studies of cancer dormancy and bone metastasis, focusing on leukaemia and breast cancer. Commonly used mouse models do not accurately mimic these key cancer hallmarks or the severity of the disease. The in vitro bone model enables long-term monitoring, facilitating the identification of mechanisms, biomarkers, and therapeutic targets. The award will also support the wider adoption of the in vitro model by other labs at the Cancer Research UK Scotland Centre where technical support and practical training for researchers will be provided to enable its use for other cancer types including prostate, lung and multiple myeloma.