Modeling of cell biology
The aim of this research area is to obtain a deeper insight into the cellular mechanism leading to exocytosis in different endocrine cells (intestinal L-cells, pancreatic beta- and alpha-cells), by a combination of experimental data and mathematical modeling.
In most of the excitable cell, the steps leading to secretion are quite similar: a trigger initiates the electrical activity in the cell, which leads to the opening of voltage gated calcium channels and a subsequent calcium influx inside the cell; the increase in calcium levels allows the vesicles to fuse with the plasma membrane and to release their content outside the cell.
- Modeling of electrophysiology:
In intestinal L-cells, our goal is to investigate the stimulus-secretion pathway and the interaction of two glucose–sensing mechanisms: the sodium-glucose cotransporters (SGLT) and ATP-sensitive K+-channels.
In human beta-cells, our aim is to investigated the heterogeneous and non-intuitive electrophysiological responses to ion channel antagonists. We also study paracrine signals, and simulated slow oscillations by adding a glycolytic oscillatory component to the electrophysiological model.
In alpha-cells, the electrophysiological regulation is still controversial and a consensus model is not available. Interestingly, alpha-cells share many ion channels with beta-cells but respond to glucose in the opposite way. Our research focuses on building a mathematical model of electrical activity in alpha-cells to interpret the experimental data.
- Modeling of calcium dynamics and exocytosis:
We use a modeling program “CalC” to simulated calcium diffusion and buffering inside the cell, as a result of Ca2+-channel opening during depolarization. By coupling the calcium diffusion simulations to a simple model for insulin granule exocytosis, our aim is to investigate the fusion probability in different pools of granules, as function of vicinity to the Ca2+-channel and calcium affinity. “CalC” simulations are an useful tool to analyze data from insulin-secreting cells, alpha cells and pituitary cells.
- Multiscale modeling.