The global analysis of liver protein complexes during the response to intermittent fasting

Summary

In animals, short periods of nutrient deprivation, such as intermittent fasting, have been shown to provide benefits with regard to cancer risk/treatment and ageing. Our aims are to identify how this is occurring at the protein-level in the liver, a key metabolic hub. To achieve this, we use state-of-the-art quantitative proteomics to give an unprecedented insight into protein identity, abundance, and most importantly their interactions.

Supervisor(s)

Dr Mark Larance

Research Location

Charles Perkins Centre – the Judith and David Coffey Life Lab

Program Type

PHD

Synopsis

Proteins regulate all cellular processes including those modulated by intermittent fasting such as cell proliferation, metabolism, stress responses and the ageing process. The regulation of protein function can be mediated by changing their abundance, interactions, subcellular localisation and/or post-translational modifications. To date, genetic analysis has been used to identify important pathways mediating the effects of intermittent fasting such as the insulin/IGF-1 and mTOR signalling pathways, but has been limited in power due to the large number of downstream processes and pathways involved in the beneficial effects. In addition, a number of proteins involved in the response to intermittent fasting (e.g. mTOR) are known to be regulated by protein-protein interactions, but the exact mechanism of regulation has not been fully elucidated. In this project state-of-the-art quantitative proteomics will be utilised to give an unprecedented insight into proteins and their interactions during intermittent fasting in mouse liver. We have already identified many significant protein abundance changes after a single bout of fasting in several novel and unexpected areas including chromatin proteins and histone modifications. We also observed a number of key enzymes in metabolism, ubiquitin-signalling and nuclear-cytoplasmic transport altering their protein-protein interactions without changing abundance. Such regulation would have been missed using standard approaches. This project will allow us to identify the pathways underlying the benefits of intermittent fasting and their mechanisms of regulation.

Additional Information

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

  • Confidential disclosure and registration of a disability that may hinder your performance in your degree;
  • Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
  • Ability to perform independently and/or with minimal supervision;
  • Ability to undertake certain physical tasks (e.g. heavy lifting);
  • Ability to undertake observatory, sensory and communication tasks;
  • Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
  • Ability to work in confined spaces or at heights;
  • Ability to operate heavy machinery (e.g. farming equipment);
  • Hold or acquire an Australian driver’s licence;
  • Hold a current scuba diving license;
  • Hold a current Working with Children Check;
  • Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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Keywords

metabolism, fasting, Liver, mouse, mass spectrometry, Biochemistry, Proteomics, Proteins, Chromatography, Statistics, data analytics, machine learning.

Opportunity ID

The opportunity ID for this research opportunity is: 2150

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