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Understanding the leukaemic niche: computational modeling of intercellular signaling networks in the bone marrow microenvironment

了解白血病生态位：骨髓微环境中细胞间信号网络的计算模型

基本信息

批准号：
2127296
负责人：
金额：
--
依托单位：
University of Glasgow
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2127296
关键词：
Understanding leukaemic niche computational modeling

项目摘要

Studentship strategic priority area:Quantitative Systems MedicineKeywords: scRNA-Seq, Cell-cell communication, computational modelling, cancerChronic myeloid leukaemia (CML) is caused by a population of oncogene expressing stem cells resident in the bone marrow (BM) of patients. There is increasing evidence that these leukaemic stem cells (LSC) disrupt the BM microenvironment or "niche" to maintain the disease, and that this is achieved through altered ligand/receptor signaling between particular cellular populations. The overarching objective of this exciting interdisciplinary project is to identify which interactions are deregulated in the leukaemic BM, thereby identifying novel therapeutic interventions for the clinic.The DTP candidate will develop, optimize and test novel computational methodologies to construct a probabilistic intercellular signaling network between relevant cellular populations in the normal BM niche using multiple, publicly-available scRNA-seq datasets. They will then incorporate expression data generated from primary CML samples to assess how this network is perturbed in the presence of LSC and ultimately identify potential targets for novel therapeutic intervention in this disease. Of particular interest is a stratified patient cohort exhibiting a poor response to current treatments. This exciting and clinically focused project will offer the DTP candidate the opportunity to gain both computational and experimental skills, and will be supervised by an interdisciplinary team between the Universities of Glasgow and Edinburgh.

学生战略优先领域：定量系统医学关键词：scRNA-Seq，细胞-细胞通讯，计算模型，癌症慢性髓系白血病(CML)是由患者骨髓(BM)中表达干细胞的癌基因群体引起的。越来越多的证据表明，这些白血病干细胞(LSC)破坏了骨髓微环境或“生态位”以维持疾病，这是通过改变特定细胞群体之间的配体/受体信号来实现的。这个激动人心的跨学科项目的首要目标是确定白血病骨髓中哪些相互作用被解除管制，从而确定临床上新的治疗干预措施。DTP候选人将开发、优化和测试新的计算方法，以使用多个公开可用的scRNA-seq数据集在正常骨髓利基中的相关细胞群体之间构建概率细胞间信号网络。然后，他们将结合从初级CML样本产生的表达数据，以评估这个网络在LSC存在时是如何受到干扰的，并最终确定这种疾病的新治疗干预的潜在靶点。特别令人感兴趣的是，一个对当前治疗反应不佳的分层患者队列。这个令人兴奋的、专注于临床的项目将为DTP候选人提供获得计算和实验技能的机会，并将由格拉斯哥大学和爱丁堡大学之间的一个跨学科团队监督。