Who´s the boss? Outlining the regulatory network of insulin-secreting b-cells

In the human pancreas, beta-cells secrete insulin in a pulsatile manner upon raised glucose concentration, a key feature lost in patients with type II diabetes. The beta-cell behavior is coordinated and suggested to depend on two oscillators, one electrical and one metabolic.

The mechanisms underlying this behavior are poorly understood, as the complex system involves individual and population-level interactions, and the tools to study such interactions are still missing.To address this issue, we will create a toolbox of technologies, including microfluidics, advanced imaging, image analysis, and graph theory-based signal analysis, to simultaneously generate single-cell and population data and monitor cells over time.

Additionally, we will use simulations that combine systems biology with extracellular cues to support experimental findings.

Our imaging analysis tool, based on neural networks and virtual staining, will allow long-term, probe-free monitoring of cells.

This research aims to identify the robustness of coordinated beta-cell behavior, determine which oscillator dominates in different conditions, and describe the transition between non-synchronized and coherent cell behavior to understand beta-cell system regulation.

Ultimately, our findings could lead to identifying novel regulatory targets for therapeutic interventions in diagnosing and treating type II diabetes patients.