Understanding the importance of location within the tumour-bone microenvironment

大多数癌症死亡是由于转移，骨是许多常见癌症的主要转移部位。因此，在这种专门的环境中对复杂的细胞相互作用进行建模对于开发新的治疗方法至关重要。这些相互作用是驱动许多关键特征的关键，包括肿瘤的生长和存活、休眠、骨骼疾病和耐药性，并支持一旦肿瘤扩散到骨骼，不可避免的致命结果。越来越多的证据支持细胞位置在骨骼微环境中的重要性。该项目汇集了爱德华兹教授和沃尔什教授在骨肿瘤学和工程学/微流体学方面的独特专业知识。利用最先进的微流控设备(3-5)，本项目将研究肿瘤细胞与骨骼微环境细胞之间的相互作用。微流控装置将有助于研究骨微环境对转移的影响，使研究癌细胞的异质性和多种细胞类型的培养成为可能。这个项目将提供一个独特的多学科机会，在肿瘤生物学和工程学的研究领域工作。将使用最先进的方法，包括先进的细胞培养系统、微流控设备、RNA测序、CRISPR/Cas9介导的基因编辑。这种学习方式将为学生获得技能提供广泛的机会。该项目的目标是使用最先进的生物工程方法来询问肿瘤骨骼微环境，并确定新的治疗目标，用于治疗目前致命的骨骼恶性肿瘤，如多发性骨髓瘤和前列腺癌骨转移。因此，该项目将解决以下MRC战略技能优先事项。定量技能：学生将接受关于下一代测序数据分析的广泛培训，以及数据分析和统计培训。跨学科技能：学生将接受最先进的骨肿瘤学和生物工程技术培训，包括结合患者样本，从而形成连接肿瘤学、生物工程学和临床的跨学科方法。整体生理学：学生将利用骨肿瘤学的活体模型，促进对肿瘤-骨微环境的全面研究。

The majority of cancer deaths are due to metastasis, with bone being a major metastatic site for many common cancers. As such, modelling the complex cellular interactions within this specialised environment is essential for the development of new therapies. These interactions are key to driving many of the key features, including tumour growth and survival, dormancy, bone disease and drug resistance, and underpin the inevitably fatal outcome once tumours spread to bone. There is increasing evidence to support the importance of cellular location within the bone microenvironment. This project brings together the unique expertise of Profs Edwards and Walsh in bone oncology and engineering/microfluidics. Using state-of-the-art microfluidic devices(3-5), this project will study the interactions between tumour cells and cells of the bone microenvironment. Microfluidic devices will facilitate the study of the effect of the bone microenvironment on metastasis, enabling the investigation of cancer cell heterogeneity and the culture of multiple cell types. This project will provide a unique multidisciplinary opportunity, working within the research fields of tumour biology and engineering. State-of-the-art approaches will be used, including advanced cell culture systems, microfluidic devices, RNA-Sequencing, CRISPR/Cas9-mediated gene editing. This studentship will provide extensive opportunities for skill acquisition by the student. The goal of the project is to use state-of-the-art bioengineering approaches to interrogate the tumour-bone microenvironment and identify new therapeutic targets for the treatment of currently fatal skeletal malignancies such as multiple myeloma and prostate cancer bone metastases. As such, the project will address the following MRC strategic skill priorities. Quantitative skills: The student will undertake extensive training on analysis of next generation sequencing data as well as data analysis and statistical training. Interdisciplinary skills: The student will receive training in state-of-the-art techniques in bone oncology and bioengineering, including incorporating patient samples and therefore resulting in an interdisciplinary approach bridging oncology, bioengineering and the clinic. Whole organism physiology: The student will utilise in vivo models of bone oncology, facilitating a comprehensive study of the tumour-bone microenvironment.