Integration of in vivo Ca2+ signalling at the organ, cell and subcellular level in anesthetized and awake animals applying the pancreatic islet as a unique model system
Description: The objective is to decipher mechanistically how the pancreatic islet microorgan integrates Ca2+ signalling at the individual cell and subcellular level under in vivo conditions in both anesthetized and awake animals under physiological and pathological conditions. Five aims will be addressed: Aim 1 will characterize how in vivo Ca2+ signalling is integrated within the pancreatic islet at the islet, cell and subcellular level. Aim 2 will reveal how different signals generated within the pancreatic islet in vivo affects integration of Ca2+ signaling. Aim 3 will clarify the interplay between Cavβ3 and Ca2+handling by endoplasmic reticulum (ER) and mitochondria. Aim 4 will decipher potential disturbances in integration of pancreatic islet Ca2+ signalling at the cell and subcellular level in vivo under conditions of prediabetes and premature ageing. Aim 5 will apply 3D in vivo imaging of Ca2+ oscillation patterns in beta cells of genetically engineered human stem-cell derived islets and further develop adequate tools for imaging and data analysis. Aims 1 and 2 will be implemented during year 1, aim 3 during year 2, aim 4 during years 3 and 4 and aim 5 during years 4 and 5. I will lead and direct the project. We have the expertise and state-of-the-art technologies to conduct the project. This project will generate results of paramount importance for diabetes but also for a more general understanding of how Ca2+ signaling is integrated at the organ, cell and subcellular level.
Funder: Vetenskapsrådet
Amount: SEK 5,400,000
Funding type: research
Funder scheme: Project grant
Start date: 2026-01-01
End date: 2029-12-31
Investigator: Per-Olof Berggren
Institution: Karolinska Institutet
Funded outputs count: 0
Funder award ID: 2025-02653
OpenAlex ID: G5628808982