Our lab aims to solve medically relevant basic biological questions, focusing on Non-canonical Notch signaling and Wnt/Notch crosstalk in development, homeostasis 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 Non-canonical Notch ligand signaling. To achieve this, we use CRISPR/Cas9 based technologies, together with scRNA seq and MS-Chip omics in mouse and human cell lines, as well as manipulation of relevant genes in the mouse model.
Aim of the proposed project is to define and functionally test the direct Wnt-Notch pathways interactions through the Notch receptor intracellular domain (NICD) in mammals.
The cross-talk between Notch and Wnt/β-catenin signaling became so integral that a joint name Wntch was proposed based on studies in Drosophila (1,2). However, its function and mechanism in mammals remain largely elusive. Successful applicant will use a combination of molecular biology methods to reveal and modify the amino acids required for interaction of Notch1/Notch2 ICDs with either β-catenin, Gsk-3β, Dvl2/WWP2, Axin or Apc, and test the outcomes on “Canonical” Notch and Wnt signaling. Applicant will mutate the respective binding motifs in either Notch1 or Notch2 genes in vivo using a mouse model to understand their patho/physiological importance in development, adulthood and cancer. In parallel, the project involves usage of newly developed cell lines in search for novel binding partners, and gene targets using MS-Chip technology.
Student will be encouraged and supported in seeking additional fellowship funding and collaborative projects abroad. Position is funded by PRIMUS grant.
Techniques: confocal microscopy, gene targeting, mouse in vivo experiments, cloning, WB, ISH immunoprecipitation, sc-RNA-seq, MS-Chip.
Requirements: Msc. student with a background in developmental or molecular biology, experience with cell cultures/animal handling/bioinformatics is beneficial.
1. Hayward, P., Kalmar, T. & Arias, A. M. Development 135, 411–24 (2008).
2. Couso, J. P. & Arias, A. M. Cell 79, 259–272 (1994).Apply to the project