Research
SBI
Systems Biology Ireland (SBI), under the leadership of Professor Walter Kolch at UCD, in collaboration with National University of Ireland in Galway, carries out cutting-edge research focused on unravelling the complexity of biological systems and improving the biomedical application of stem cells.
SBI research projects are driven by the need to address biological questions for tangible benefits. In order to achieve a systems level understanding, the conceptual framework to rationalise complex biological relationships will come from mathematical modelling. As a result, SBI’s work focuses on:
WP-1: Developing the Modelling Frameworks
Modelling frameworks is tightly linked with all other work-packages and acts as an under-lying and enabling platform for the other four work-packages to achieve the overall aim of the programme - determining how biochemical signalling networks programme biological decisions in cells, in particular in stem cells.
WP-2: MAPK and RTK signalling in cell fate decisions
Investigates the mechanisms which enable biochemical pathways to make biological decisions and aims to derive design principles that will enable us to understand cell behaviour with a long term goal of manipulating this behaviour.
WP-3: Hypoxia Signalling In Mesenchymal Stem Cells
Oxygen deprivation (hypoxia) is a key feature of the environment into which therapeutic stem cells are introduced. We and others have found that such hypoxia can have profound implications for survival, differentiation and proliferation of cells. In this work package, we will use experimental work combined with mathematical modelling to interrogate the signalling pathways in stem cells which are responsive to hypoxia and which determine stem cell fate. A greater understanding of these processes will allow us to develop new interventions which enhance the therapeutic efficacy of stem cells.
WP-4: Stem Cell Commitment: Transcriptional Networks
Mesenchymal stem cells (MSCs) can be directed to differentiate into various cell types that produce different tissues including fat, bone and cartilage. The ability to differentiate along the cartilage forming lineage, a process called chondrogenesis, provides great potential for improving cell-based therapies for joint disease and injury. This workpackage will define in very high resolution the changes in gene expression that orchestrate the commitment of MSC’s specifically to the chondrogenic lineage. The association of enzymes that control gene expression, called transcription factors, with particular groups of regulated genes will be determined using computational and bioinformatic methods, and tested using molecular and biochemical methods. Gene regulatory networks associated with chondrogenesis will be assembled that define the nuclear and cellular mechanisms that promote cartilage growth and maintenance. This will inform us on the most effective conditioning or treatment of MSCs for enhanced chondrogenesis which may then translate to optimal cartilage repair strategies.
WP-5 Host-Cell Interactions: Chemotatic Networks
Investigates the chemotactic response in host-cell interactions in transplanted stem cells with the overall aim of modelling the chemotactic response in mammalian cells. To understand the interplay of biochemical signalling networks that influence stem cell cytoskeletal rearrangements and resultant chemotaxis. From a therapeutic perspective, a full understanding of these pathways will lead to the development of optimised cellular therapies where tissue specific delivery and enhanced engraftment will be possible
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A profile of the programme can be found here.