Imaging metabolic heterogeneity in Glioblastoma

点击翻译按钮获取中文摘要

GBM is a fast-growing and invasive type of brain tumour with a poor prognosis, with an average survival time of only 12-18 months. Through this project we aim to understand more about the mechanisms of tumour progression that can provide new insights into early diagnosis and treatment strategies.Using a preclinical model of GBM as well as human tissues resected during surgery, we will explore the heterogeneity of metabolic processes across thin sections of these tumours. In collaboration with Waters UK, we will use DESI-Mass Spectrometry Imaging to image metabolites in tissue sections at high spatial resolution. The rich datasets generated by this approach will be mined to further our understanding of tumour metabolism and provide insights into potential new treatments. We will work with the wider mass spectrometry imaging community, particularly Professor Nick Lockyer's group, equipped with both MALDI and SIMS imaging mass spectrometers. The project will involve collaboration with Dr Kevin Couper's group, who will map the same tissues using Imaging Mass Cytometry allowing identification of cell types and their distribution within the tumours and surrounding tissues. We will also collaborate with Prof. David Wedge's bioinformatics group who will support computational aspects of the work. The research will focus mainly on the use of DESI-IMS for metabolic imaging and the comparison of DESI imaging data with other modalities IMC, microscopy etc. It will therefore involve co-registration and data merging from images across modalities. Using automated slide changing technology, multiple images can be acquired, allowing the construction of 3D images, where serial tissue sections are available.The student will be based at the Wolfson Molecular Imaging Centre, on the site of the Christie Hospital, where we have a Waters XEVO DESI instrument capable of more than 10 micron spatial resolution and associated tissue processing capabilities. The student will perform placement work at Waters' laboratories in Wilmslow, where they will have access to further state of the art mass spectrometry instrumentation and technical support.The project will be cross-disciplinary, developing skills and knowledge in the interpretation of mass spectra, image analysis, and an understanding the associated cancer biology. Candidates should have a background in the physical or biological sciences, with an interest in developing their expertise across these sub-disciplines.