UH Biocomputation Group - Alireza Poshtkohihttp://biocomputation.herts.ac.uk/2023-10-16T19:01:33+01:00Mathematical Modelling of Plasma Membrane Electrophysiology and Calcium Dynamics in Microglia2023-10-16T19:01:33+01:002023-10-16T19:01:33+01:00Alireza Poshtkohitag:biocomputation.herts.ac.uk,2023-10-16:/2023/10/16/mathematical-modelling-of-plasma-membrane-electrophysiology-and-calcium-dynamics-in-microglia.html<p class="first last">Alireza Poshtkohi's Journal Club session where he will talk about his PhD research in the talk entitled: "Mathematical Modelling of Plasma Membrane Electrophysiology and Calcium Dynamics in Microglia".</p>
<p>On this week's Journal Club session, Alireza Poshtkohi will talk about his PhD research in the talk entitled: "Mathematical Modelling of Plasma Membrane Electrophysiology and Calcium Dynamics in Microglia".</p>
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<p>Microglia, a type of glial cell, perform many tasks while interacting with neurons,
astrocytes, and oligodendrocytes. Despite moderate advances in the characterisation of
microglia in laboratory rodents, very little information is known about the physiology of
microglia in the human brain. This is a challenging task and consequently this research
attempts to advance knowledge of microglia function through mathematical modelling.
Microglia restructure their intracellular actin cytoskeleton to enable motility; this
requires a complex molecular cascade involving a set of ionic channels, membrane-coupled
receptors, and cytosolic components. In this research, we develop a theoretical foundation
for studying P2-mediated calcium and PI3K/Akt signalling in human microglial cells.
Firstly, a detailed mathematical model is built for the dynamics of human P2XRs in
microglia. Subsequently, experimental whole-cell currents are used to derive the
P2X-mediated electrophysiology of human microglia (sodium and calcium dynamics, and
membrane potential). Secondly, 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 the PI3K/Akt pathway. This work addresses the
development of mathematical models for these two complex aspects of microglial functions
and investigates the interconnecting role of PI3K pathway to Ca2+.
Our predictions reveal new quantitative insights into how P2Rs regulate ionic concentrations
in terms of physiological interactions and transient responses. Simulation results show that
kink-like, intricate Ca2+ responses mediated by P2XRs arise from a complex cooperative
activation of both P2XRs, and ionic extruders and pumps. More importantly, the proposed
model supports our hypothesis that calcium influx via P2YR and P2XR can explain the
experimentally observed twin peaks in the phosphorylated Akt. To the best of our
knowledge, this is the first biophysical model that aims to predict complicated Akt and
P2-mediated Ca2+ responses in microglia. The biophysical models provide direction for new
fundamental experimental research.</p>
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<p>References:</p>
<ul class="simple">
<li>A. Poshtkohi, J. Wade, L. McDaid, J. Liu, M. Dallas, A. Bithell, <a class="reference external" href="https://doi.org/10.1371/journal.pcbi.1009520">"Mathematical modelling of human P2X-mediated plasma membrane electrophysiology and calcium dynamics in microglia"</a>, 2021, PLOS Computational Biology, 17, e1009520</li>
<li>A. Poshtkoh, <a class="reference external" href="https://pure.ulster.ac.uk/ws/portalfiles/portal/124021599/2023PoshtkohiAPhD.pdf">"Computational Modelling of Plasma Membrane Electrophysiology and Calcium Dynamics in Microglia"</a>, 2023, University of Ulster,</li>
</ul>
<p><strong>Date:</strong> 2023/10/20 <br />
<strong>Time:</strong> 14:00 <br />
<strong>Location</strong>: LJ115 & online</p>