Molecular tumour profiling by mass spectrometry (MS)
Lead Research Organisation:
University of Manchester
Department Name: School of Health Sciences
Abstract
The primary focus of this study will be investigation of molecular/mass spectral signatures associated with glioblastomas, a disease with a median survival rate of less than 15 months. The team will work with the clinical neuro-oncology team, accessing biopsy and resected tumour samples that have been imaged in vivo by PET and MR and ex vivo by immunohistochemistry and genetic profiling. Passages of these human-derived cell lines will be used to follow tumour evolution in preclinical xenograft models. The project therefore provides excellent multimodality data for comparison with the MS spectra and images.
Collaborating with scientists at Waters (a University of Manchester strategic partner) will give access to both Desorption Electrospray Mass Spectrometry (DESI) and Rapid Evaporative Ionization Mass Spectrometry (REIMS) instrumentation. DESI and REIMS allow acquisition of mass spectra and MS images of tissues at ambient temperature, complementing other histopathological techniques. Our goal is to further develop tumour characterisation in terms of the heterogeneity of the tumour molecular/MS signature, through access to these new MS probe/imaging technologies, using multivariate statistical approaches to differentiate phenotypes within and between tumours, correlating the corresponding mass spectral signatures with data from the other imaging modalities and genetic profiles.
We will test the hypothesis that MS interrogation of tumour samples can assist early diagnosis, surgical decision-making and the better understanding of mechanisms of disease progression. Outcomes will include a better understanding of tumour heterogeneity and evolution as well as the nature of the molecular signatures that characterise that heterogeneity or changes over time. We aim to better understand tissue spectra enhancing the capabilities of REIMS and DESI as tools for tumour staging, subtype identification and facilitate development of in situ probe technologies allowing tissue sampling in real-time during surgical procedures.
Waters will also contribute in the form of a Case award.
Collaborating with scientists at Waters (a University of Manchester strategic partner) will give access to both Desorption Electrospray Mass Spectrometry (DESI) and Rapid Evaporative Ionization Mass Spectrometry (REIMS) instrumentation. DESI and REIMS allow acquisition of mass spectra and MS images of tissues at ambient temperature, complementing other histopathological techniques. Our goal is to further develop tumour characterisation in terms of the heterogeneity of the tumour molecular/MS signature, through access to these new MS probe/imaging technologies, using multivariate statistical approaches to differentiate phenotypes within and between tumours, correlating the corresponding mass spectral signatures with data from the other imaging modalities and genetic profiles.
We will test the hypothesis that MS interrogation of tumour samples can assist early diagnosis, surgical decision-making and the better understanding of mechanisms of disease progression. Outcomes will include a better understanding of tumour heterogeneity and evolution as well as the nature of the molecular signatures that characterise that heterogeneity or changes over time. We aim to better understand tissue spectra enhancing the capabilities of REIMS and DESI as tools for tumour staging, subtype identification and facilitate development of in situ probe technologies allowing tissue sampling in real-time during surgical procedures.
Waters will also contribute in the form of a Case award.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013751/1 | 01/10/2016 | 30/09/2025 | |||
| 1790135 | Studentship | MR/N013751/1 | 01/10/2016 | 30/06/2020 | Matthew Gentry |
| Description | International mass spectrometry socity conference travel grant |
| Amount | € 200 (EUR) |
| Organisation | International Mass Spectrometry Foundation |
| Department | International mass spectrometry society |
| Sector | Charity/Non Profit |
| Country | Netherlands |
| Start | 09/2018 |
| End | 09/2018 |
| Description | MRC DTP Flexible Training Supplement |
| Amount | £3,500 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2017 |
| End | 07/2018 |
| Description | Multi-omics study of an invasive murine model of glioblastoma |
| Organisation | Sheffield Hallam University |
| Department | Biomedical Research Centre (BMRC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | As part of this study, I run the majority of the study analysis including DESI-MSI, micro-proteomics and LA-ICP-MS imaging experiments. |
| Collaborator Contribution | The University of Glasgow - provided the animals and in vivo GBM model, including implanting and upkeep of the animals. They also sectioned the brains of the animals, undertook H&E staining and HLA staining as well as providing expertise in MRI of the mice prior to culling. MRI scans were performed in Glasgow (costs covered by UoM) with images transformed in Matlab by the Glasgow team as well as cross localisation with other imaging data sets. Sheffield Hallam University - provided time, training and expertise on their LA-ICP-MS system for analysis of tissue sections. |
| Impact | This work is currently ongoing with the view for publication outputs and contribution to my thesis. This collaboration is multi-disciplinary covering many imaging modalities (MRI, DESI-MSI, LA-ICP-MSI) as mentioned above. |
| Start Year | 2019 |
| Description | Multi-omics study of an invasive murine model of glioblastoma |
| Organisation | University of Glasgow |
| Department | Institute of Cancer Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | As part of this study, I run the majority of the study analysis including DESI-MSI, micro-proteomics and LA-ICP-MS imaging experiments. |
| Collaborator Contribution | The University of Glasgow - provided the animals and in vivo GBM model, including implanting and upkeep of the animals. They also sectioned the brains of the animals, undertook H&E staining and HLA staining as well as providing expertise in MRI of the mice prior to culling. MRI scans were performed in Glasgow (costs covered by UoM) with images transformed in Matlab by the Glasgow team as well as cross localisation with other imaging data sets. Sheffield Hallam University - provided time, training and expertise on their LA-ICP-MS system for analysis of tissue sections. |
| Impact | This work is currently ongoing with the view for publication outputs and contribution to my thesis. This collaboration is multi-disciplinary covering many imaging modalities (MRI, DESI-MSI, LA-ICP-MSI) as mentioned above. |
| Start Year | 2019 |