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EMBO Long-Term Fellowship 2nd year
Third-party funded project
Project title EMBO Long-Term Fellowship 2nd year
Principal Investigator(s) Hall, Michael N.
Co-Investigator(s) Shetty, Sunil
Organisation / Research unit Departement Biozentrum / Biochemistry (Hall)
Project start 01.09.2017
Probable end 31.08.2018
Status Completed
Abstract

Depending on environmental conditions, a cell modulates translation of specific mRNAs for optimal survival. The best-characterized sensor of environmental conditions that controls cellular growth is mammalian Target of Rapamycin (mTOR) that is known to regulate translation as well as ribosome biogenesis, although the exact mechanism is unclear. The mTOR pathway is upregulated in most cancers including hepatocellular carcinoma (HCC) and is also implicated in metabolic disorders such as obesity and diabetes. The liver is the most important organ that senses changes in global physiology and maintains homeostasis. The efficient sensing of and response to changes in blood composition by hepatocytes need robust regulation of translation and transcription. For such regulation, the modulation of ribosome composition and its interaction with various factors like RNA-binding proteins (RBPs) has been speculated. Interestingly, metabolic enzymes like Aconitase I can also act as RBPs and modulate gene expression in response to diverse metabolic changes. We aim to identify ribosomal factors as well as novel RBPs in liver cancer which might assists in mTOR mediated regulation. Using a series of approaches like polysome profiling, mass spectrometry, PAR-CL and genetic analyses in animal model systems, we intend to decipher the novel regulatory mechanisms in liver.

Keywords Specialized ribosomes, RNA Binding Proteins (enigmRBPs), Ribosome heterogeneity, mTOR complexes, Obesity, Hepatocellular carcinoma (Liver cancer)
Financed by Other sources
   

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20/04/2024