Understanding the leukaemic niche: computational modeling of intercellular signaling networks in the bone marrow microenvironment
Lead Research Organisation:
University of Glasgow
Department Name: College of Medical, Veterinary, Life Sci
Abstract
Studentship strategic priority area:Quantitative Systems Medicine
Keywords: scRNA-Seq, Cell-cell communication, computational modelling, cancer
Chronic 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.
Keywords: scRNA-Seq, Cell-cell communication, computational modelling, cancer
Chronic 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.
