Mathematical modelling and computer simulation are powerful tools by which we can analyse complex biological systems, particularly, neural phenomena involved in brain dysfunction. In this research, we develop a theoretical foundation for studying P2-mediated calcium and PI3K/Akt signalling in human microglial cells. Microglia, which are brain-resident macrophages, restructure their intracellular actin cytoskeleton to enable motility; this restructuring requires a complex molecular cascade involving a set of ionic channels, membrane-coupled receptors, and cytosolic components. Recent studies highlight the importance of increasing our understanding of microglia physiology since their functions play critical roles in both normal physiological and pathological dynamics of the brain. There is a need to develop reliable human cellular models to investigate the biology of microglia aimed at understanding the influence of purinergic signalling in brain dysfunction to provide novel drug discovery targets.
In this work, a detailed mathematical model is built for the dynamics of human P2XRs in microglia. Subsequently, experimental whole-cell currents are used to derive P2X-mediated electrophysiology of human microglia (i.e., sodium and calcium dynamics, and membrane potential). Our predictions reveal new quantitative insights into P2XRs on how they regulate ionic concentrations in terms of physiological interactions and transient responses. The developed model is given under the directory human-P2X-electrophysiology-in-microglia.
Microglial-directed motility involves a complex family of intracellular signalling pathways that are mainly controlled by P2Y-mediated cytosolic calcium (Ca2+) signalling and activation of PI3K/Akt pathway. Another objective of this research is to develop mathematical models for these two complex intracellular events and investigate the interconnecting role of PI3K pathway to Ca2+. This part of the project is in progress and the source codes will be added in the near future.
Licence: Note that the code can be changed and reused as long as you keep the copyright inside and at the beginning of source files in the source directory unchanged. If this project is used in a research that ends up with a publication, it should be cited as the reference given under every corresponding directory.