Research Area: Signalling pathways in cell and tissue homeostasis
Throughout an animal’s lifetime, cells must continuously react to the changing environment and coordinate their behaviors to maintain tissue homeostasis and function. They do so by activating signal transduction pathways that evoke changes in gene expression. The rapid switch of cellular transcriptome requires the activity of specific transcription factors and precise processing of the native pre-mRNAs by the spliceosome. The aberrant gene expression as a consequence of transcription factor and/or spliceosome malfunction hallmarks age-associated tissue decline and a wide range of diseases including neurodegeneration, cancer and chronic inflammatory disorders. Unraveling how transcription factors and pre-mRNA splicing control distinct cellular fates and maintain tissue homeostasis under normal and stress conditions is essential for understanding their roles in disease etiology and aging.
Our group elucidates the pleiotropic functions of the stress-inducible signaling pathways and downstream mechanisms governing gene expression in the physiological and pathological contexts. We study how mechanical stress and loss of polarity impact signaling cascades and transcription factor networks involved in the regulation of growth, differentiation and defense responses in the epithelial tissues. We are interested in understanding how stress affects spliceosome assembly and splicing accuracy as spliceosome malfunctions pose a significant challenge to the cells and thread to genome integrity. We focus on mechanisms that collaborate with the pre-mRNA processing machinery to generate cell type specific splicing patterns. We use genetic and molecular approaches to identify the stress-inducible and DNA damage related genetic networks that respond to spliceosome deregulation and decipher how they contribute to loss of tissue homeostasis, premature aging and disease phenotypes.
The projects available in our group are tailored to fit our continuous efforts to elucidate the molecular mechanisms that link stress signaling to the regulation of gene expression and the maintenance of genome integrity during development, aging and diseases.
The projects will develop around the following themes:
The group uses Drosophila and mouse models, insect and mammalian cultured cells. We combine genetics and genome engineering (CRISPR/Cas9) with a wide range of cell and molecular biology techniques, advanced microscopy and live imaging, biochemistry, genomic (RNA-seq, DamID, ChIP-seq) and proteomic approaches.
We seek curious, motivated and reliable candidates with a strong theoretical background in genetics, molecular and cell biology and previous hands-on lab experience. Good communication skills and fluency in spoken and written English are desirable. Experience with Drosophila or mouse models is an advantage.