Stocker lab, Master Thesis Project on impact of amino acids on tumor growth

Background

The lipid phosphatase PTEN is one of the most commonly mutated tumor suppressors in human cancer.  As a negative regulator of insulin/PI3K/AKT signaling, PTEN inhibits cell growth, proliferation, and survival. Whereas nutrient restriction (NR) has a life-prolonging and anti-tumorigenic effect, constitutive activation of PI3K/AKT signaling (e.g. by the loss of PTEN) renders tumors insensitive to NR.

By inducing homozygous mutant cells in developing Drosophila imaginal discs, we study the function of PTEN in a proliferating tissue. We apply NR during the growth phase by reducing the concentration of yeast (the main source of amino acids) in the food. Cells lacking PTEN in Drosophila imaginal discs hyperproliferate massively upon NR, culminating in the outcompetition of surrounding wild-type tissue. Interestingly, RNA-seq data of PTEN mutant eye imaginal discs revealed an upregulation of genes coding for amino acid transporters and receptors.

Project

In order to identify amino acids whose limitation causes the hyperproliferation of PTEN mutant cells upon NR, we will perform feeding experiments in which single amino acids or suitable combinations of amino acids will be added to the NR food. Furthermore, we will analyze the influence of amino acid transporters and receptors in an RNAi-based co-knockdown assay to assess whether those transporters and receptors are limiting for the overgrowth of PTEN mutant cells.

Methods

Light microscopy, confocal microscopy, fly genetics, stress experiments

Start

Position immediately available

Duration

6 months – open to extension

For further information please contact Dr. Hugo Stocker () or Susanna Hempel ().