High throughtput electrophysiological measurements coupled with transcriptomics to reveal cellular dysfunction in type 2 diabetes

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 - and -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 - and -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.