Postdoc Fellowships 2023 - Project 1

Research Project

Integrating transcriptomics and chemical biology for induction of β-cells

Diabetes features a reduction in the number of functional β-cells, a key pathologic event that causes or exacerbates the dysregulation of blood glucose levels. Regenerating insulin-producing β-cells might prove a better treatment for diabetes, which is at present controlled but not reversed by insulin injections. Therefore, the main interest in the lab of Olov Andersson is to determine how small molecules and cellular mechanisms can promote regeneration of insulin-producing beta-cells and improve metabolic control, as potential curative approaches for diabetes. The successful applicant will use chemical-genetic screening techniques in zebrafish to identify compounds, genes and signalling pathways that can promote β-cell regeneration.

Signaling between different pancreatic cell types will be identified using bioinformatics tools, and the identified pathways will be perturbed (using genetics or small molecules know to target the pathways) and assessed for involvement in progenitor maintenance or differentiation of progenitors to β-cells in zebrafish.

We will lineage-trace specific progenitor populations, as well as isolate the progenitor cells and their differentiated descendants to delineate the mechanisms of β-cell regeneration by single-cell RNA-seq. We will then perturb candidate pathways in human organoids derived from ductal cells to determine whether their effects on β-cell neogenesis are conserved across species.

The present project will span from chemical biology to genetics in zebrafish, as well as translational studies using human organoids. The studies will include assessing beta-cell neogenesis, proliferation and transdifferentiation, and how such cellular changes may affect glycemia.

The zebrafish are amenable to efficient transgenesis and high-resolution imaging. We will make use of these properties to generate transgenic, knock-in and mutant zebrafish for single-cell analysis of phenotypes and lineage tracing.

Project description

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Lab webpage

How to apply

Applications has closed, hiring in process.