Imaging metabolic heterogeneity in Glioblastoma

GBM是一种快速生长和侵袭性的脑肿瘤，预后不良，平均生存时间仅为12-18个月。通过这个项目，我们的目标是了解更多关于肿瘤进展的机制，可以为早期诊断和治疗策略提供新的见解。使用GBM的临床前模型以及手术期间切除的人体组织，我们将探索这些肿瘤薄切片上代谢过程的异质性。在与沃茨英国公司的合作中，我们将使用质谱成像技术以高空间分辨率对组织切片中的代谢物进行成像。通过这种方法产生的丰富数据集将被挖掘，以进一步了解肿瘤代谢，并为潜在的新治疗提供见解。我们将与更广泛的质谱成像社区，特别是教授尼克洛克耶的小组，配备了MALDI和西姆斯成像质谱仪。该项目将涉及与Kevin Couper博士的团队合作，该团队将使用成像质量细胞计数法绘制相同的组织，从而识别细胞类型及其在肿瘤和周围组织中的分布。我们还将与大卫韦奇教授的生物信息学小组合作，他们将支持这项工作的计算方面。该研究将主要集中在代谢成像和DESI成像数据与其他模式IMC，显微镜等的比较，使用EST-IMS，因此，它将涉及跨模式图像的配准和数据合并。使用自动换片技术，可以获得多个图像，从而可以构建3D图像，其中可以获得连续的组织切片。该学生将在位于克里斯蒂医院的沃尔夫森分子成像中心工作，在那里我们拥有一台沃茨XEVO DESI仪器，其空间分辨率超过10微米，并具有相关的组织处理能力。学生将在沃茨位于威姆斯洛的实验室实习，在那里他们将获得更先进的质谱仪器和技术支持。该项目将是跨学科的，培养质谱解释、图像分析和相关癌症生物学理解方面的技能和知识。候选人应具有物理或生物科学背景，并有兴趣在这些子学科中发展自己的专业知识。

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.