Student projects

Master thesis projects

Background: Mutations in the RNA-binding protein Bicaudal C1 (Bicc1) trigger the formation of fluid-filled renal cysts that resemble Polycystic Kidney Disease (PKD) and other incurable genetic diseases known as “ciliopathies”. Among the first direct target RNAs, we recently identified adenylate cyclase (AC)-6 mRNA (Piazon et al. 2012) which is silenced in cytoplasmic foci of Bicc1 self-polymers (Rothé et al. 2015). However, the role of Bicc1 in human PKD and the mechanism by which its self-polymerization represses the translation of target mRNAs are incompletely understood.
1. Effect of Ca2+ flux on Bicc1 protein interactions
PKD shares several hallmarks with cancer, including sustained proliferation signaling and metabolic perturbations that arise due to genetic inactivation of calcium ion channels. Functionally relevant molecular targets of calcium include the kinase CaMKII. Using a combination of proteomics and imaging, this project will assess the impact of Ca2+/CaMKII signaling on Bicc1 self-polymerization and other protein-protein interactions implicated in metabolic regulation.
2. Dynamics of cytoplasmic Bicc1 self-polymers
Fluorescent and photoconvertible Bicc1 fusion proteins will be imaged in cultured renal epithelial cells to determine the dynamics of their self-association and their regulation by interacting mRNAs and proteins.
3. Role of Bicc1 as an RNA chaperone
Using recombinant purified Bicc1 and mutant derivatives in cell-free assays, this project will test the prediction that Bicc1 functions as an mRNA chaperone to control access of miRNAs and other regulatory factors to target sites that are masked in stable RNA hairpins.
In all projects, students will gain experience in molecular and cell biology, biochemistry and imaging techniques.
Candidates should express their interest and send their credentials and CV to the lab head: [email protected]