Lab Background

Our lab aims to solve medically relevant basic biological questions, focusing on Notch signaling and Wnt/Notch crosstalk in development and disease.

We strive to achieve a better mechanistic insight into the processes co-regulated by direct protein-protein interaction between components of Notch and Wnt pathways and Notch ligand signaling. To achieve this, we use CRISPR/Cas9-based technologies, together with bulk, scRNA seq, and lineage tracing in mouse and human cell lines, as well as manipulation of relevant genes in the mouse model.

The proposed project aims to define and functionally test the intrinsic requirements of Jagged1 signaling within the subpopulations of liver perivascular mesenchyme in development and disease.

Projects take advantage of the known biliary atresia, and Allagile syndrome-causing mutations in Jagged1[1], which we recapitulated in vivo in mice. The inductive role of Jagged1 (expressed by the liver periportal mesenchymal cells) for bile duct development is well established[2], however, the nature and extent of its requirement within the mesenchymal populations is unknown. To dissect the role of Jagged1-Notch signaling in the mesenchyme, this project aims to use human disease-relevant mouse models in combination with lineage tracing and transcriptomics.

The position is a stipend + 50% contract covered by the PRIMUS/UNCE funding. Applicants will be encouraged and supported in seeking additional fellowship funding and collaborative projects abroad.

Techniques: confocal microscopy, lineage tracing, mouse in vivo experiments, cloning, WB, RNA scope, sc-RNA-seq, bulk RNAseq.

Mašek J, Andersson ER: The developmental biology of genetic Notch disorders. Development 2017, 144:1743–1763.

Hofmann JJ, Zovein AC, Koh H, Radtke F, Weinmaster G, Iruela-Arispe ML, Alagille D, Estrada A, Hadchouel M, Gautier M, et al.: Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome. Development 2010, 137:4061–72.

Requirements

Msc. student with a background in developmental and/or molecular biology. Experience with cell cultures/animal handling/bioinformatics is beneficial

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