HippoGailiteProject reference: 331192
Funded under :
Regulation of the Hippo tissue growth pathway by nutrient sensing mechanisms in Drosophila melanogaster
Total cost:EUR 221 606,4
EU contribution:EUR 221 606,4
Coordinated in:United Kingdom
Topic(s):FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development"
Call for proposal:FP7-PEOPLE-2012-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
The Hippo pathway is a highly conserved tumour suppressor pathway that restricts cell proliferation and promotes apoptosis. Although initially discovered in Drosophila, the Hippo pathway is highly conserved in mammals. Mutations and epigenetic silencing of Hippo pathway genes are frequently found in cancer tissues. Thus, our understanding of pathway regulation is important for the understanding of tumour formation and potential cancer treatments.
The upstream regulation of the Hippo pathway is complex, but until now not completely understood. In the host lab, Salt-inducible kinases (SIKs) were identified as inhibitors of the Hippo pathway. SIKs belong to the AMP-activated protein kinase (AMPK) family. AMPK family kinases are sensors of nutrient or energy status. Thus, SIKs might activate cell growth in conditions of optimal nutrient availability, thereby coupling developmental growth with nutritional status. In the proposed project I plan to investigate whether and how nutrient and energy levels regulate SIKs in context of Hippo signalling. Additionally, I will test whether other AMPK family kinases are involved in regulation of the Hippo pathway. I will use a multidisciplinary approach that encompasses whole organism nutritional assays, Drosophila genetic manipulation, cell biology, biochemistry and state-of-art imaging techniques.
The goal of the project is to elucidate the coupling between nutrient sensing and Hippo signalling. Since altered metabolism and nutrient usage is a feature of cancer cells, I believe this work will advance our understanding of oncogenic transformation. This year, the first attempts at designing cancer treatments that target the Hippo pathway in cancer tissues have emerged. Full knowledge of the details of Hippo pathway regulation will be required for a successful choice of targets and pharmacological compounds, to appreciate potential side effects and to predict the effect of currently used drugs on the Hippo pathway.
EU contribution: EUR 221 606,4
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