The tumor protein, translationally-controlled 1 (TPT1) is a multifunctional, universally conserved protein implicated as a potential drug target in human cancer therapy. TPT1 is frequently overexpressed in a variety of tumors including acute myeloid leukemia (AML), a heterogeneous disease of the myeloid compartment characterized by an accumulation of cells blocked at early stages myeloid development. TPT1 has been identified as an inhibitor auf autophagy, a process of bulk protein degradation and recycling. Since autophagy is also necessary for efficient AML differentiation therapy, the PhD project will test the hypothesis that TPT1 expression inhibits granulocyte differentiation due to decreased autophagy. The student will first establish the localization of TPT1 relative to autophagy markers during granulocyte differentiation of AML cell line models. This will be done using state of the art high throughput life and fixed cell imaging to capture the dynamics/heterogeneity and localization of TPT1 and autophagy marker expression. Subsequently, the student will analyse the consequences of genetic depletion and pharmacological inhibition of TPT1 in different AML cell line models for neutrophil differentiation and autophagy.
The PhD student will be enrolled in the Graduate School for Cellular and Biomedical Sciences (GCB; http://www.gcb.unibe.ch) at the University of Bern. This PhD project is a shared project between the Ochsenreiter/Tschan lab and the student will be involved in both research groups.