T2D-EOMICS | High throughtput electrophysiological measurements coupled with transcriptomics to reveal cellular dysfunction in type 2 diabetes

Summary
In this project, I will develop methods to simultaneously measure transcriptomes with single-cell resolution and perform high-throughput functional measurements of individual pancreatic islet cells. I will focus on β- and α-cells which regulate glucose levels by secreting the two main glucoregulatory hormones -insulin and glucagon- and whose dysfunction is associated with diabetes. The islet is a highly heterogenous mini-organ, making it an ideal tissue to study the relationship between molecular and functional heterogeneity. It has been recently developed the use of patch-clamp electrophysiology and single-cell RNA sequencing (patch-seq) using whole-cell electrophysiology. In this work, I will combine high-density microelectrode array technology (HD-MEA) and transcriptomic methods to identify changes that lead to dysfunctional cellular states in type 2 diabetes. To do so, I will build a cell cherry-picking system to perform single-cell RNA sequencing after electrophysiological measurements in the same islet cell. Then I will use this system to investigate subpopulations of α- and β-cells that have been previously identified in human islets from donors with type 2 diabetes using transcriptomic methods, but whose implications in cell and tissue function are yet unclear.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101108327
Start date: 01-04-2023
End date: 31-03-2025
Total budget - Public funding: - 206 887,00 Euro
Cordis data

Original description

In this project, I will develop methods to simultaneously measure transcriptomes with single-cell resolution and perform high-throughput functional measurements of individual pancreatic islet cells. I will focus on β- and α-cells which regulate glucose levels by secreting the two main glucoregulatory hormones -insulin and glucagon- and whose dysfunction is associated with diabetes. The islet is a highly heterogenous mini-organ, making it an ideal tissue to study the relationship between molecular and functional heterogeneity. It has been recently developed the use of patch-clamp electrophysiology and single-cell RNA sequencing (patch-seq) using whole-cell electrophysiology. In this work, I will combine high-density microelectrode array technology (HD-MEA) and transcriptomic methods to identify changes that lead to dysfunctional cellular states in type 2 diabetes. To do so, I will build a cell cherry-picking system to perform single-cell RNA sequencing after electrophysiological measurements in the same islet cell. Then I will use this system to investigate subpopulations of α- and β-cells that have been previously identified in human islets from donors with type 2 diabetes using transcriptomic methods, but whose implications in cell and tissue function are yet unclear.

Status

SIGNED

Call topic

HORIZON-MSCA-2022-PF-01-01

Update Date

31-07-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2022-PF-01
HORIZON-MSCA-2022-PF-01-01 MSCA Postdoctoral Fellowships 2022