Modelling medulloblastoma methylation in vitro
Lead Research Organisation:
University of Nottingham
Department Name: School of Medicine
Abstract
Project is to develop and characterise representative 3D models of SHH medulloblastoma. These will then be used to understand how the tumour suppressor P53 influences therapeutic response. The overall aim being to identify an effective therapeutic strategy for P53 mutated SHH medulloblastoma, which is categorised as very high risk due to very poor outcome with current therapeutic approaches.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 01/10/2015 | 31/10/2024 | |||
| 1647732 | Studentship | BB/M008770/1 | 01/10/2015 | 30/09/2019 |
| Description | Cancer cell lines are routinely grown in flasks in the lab; however, this 2D method fails to reflect the multi-dimensional growth that is observed in patient tumours. Therefore, we aimed to respond to the need for a more patient-relevant 3D model of medulloblastoma, the most common malignant paediatric brain tumour. To do this, we adopted an approach whereby medulloblastoma cells were grown in small "tumour-balls" called spheroids. By growing cells in this way, we were able to model tumour growth, as well as assess the effects of chemotherapy drugs and model tumour cells spreading over a gel mimicking the brain. |
| Exploitation Route | Our findings provide a highly-reproducible, clinically-relevant, in vitro model of medulloblastoma that can be applied by other groups in the brain tumour research field. At the moment it is readily applicable in drug assays and is already being used by industrial partners in the testing of novel therapeutic targets for medulloblastoma. In the future, this model could become more advanced, incorporating different cell types and growing the spheroids in different matrices. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | Evaluating drug response in medulloblastoma in vitro models |
| Organisation | Healx Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Our research team provided the expertise in 3D spheroid generation and drug screening in order to test a panel of novel inhibitors. |
| Collaborator Contribution | Our partner, Healx, supplied the inhibitors for testing. |
| Impact | Outputs are currently unknown - however, testing showed promising results for some inhibitors. |
| Start Year | 2019 |
| Description | Using medulloblastoma 3D spheroids to assess the utility of novel splicing kinase inhibitors |
| Organisation | University of Nottingham |
| Department | School of Life Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In collaboration with a research group in the School of Life Sciences at the University of Nottingham, the 3D spheroid model of medulloblastoma was utilised to assess novel splicing kinase inhibitors. Our input involved the transfer of our knowledge and expertise in 3D spheroid generation, maintenance and drug screening. General tasks involved experimental training in the established technique and being on hand to advise the collaborator during their experimentation with our 3D model. |
| Collaborator Contribution | Our collaborator in the School of Life Sciences contributed the novel splicing kinase inhibitors. |
| Impact | The work will be presented at an international conference by the collaborator. |
| Start Year | 2019 |
| Description | "Wonder" (University-wide public engagement event) |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | "Wonder" is a University of Nottingham public engagement event whereby the local community can visit campus for a day to learn more about ongoing research. Researchers at the Children's Brain Tumour Research Centre engage with children through teaching basic lab skills, e.g. pipetting and using a microscope, and find that all of the children are enthusiastic about science. It also gives us an opportunity to talk to parents about brain tumours (a topic too heavy for children) and this usually leads to interesting conversations about our research. At Wonder, there is also the chance to meet with patient groups and charitable donors and is therefore a great opportunity to thank those who support our work. |
| Year(s) Of Engagement Activity | 2018,2019 |