Metabolic control by Short-Chain Fatty Acids (SCFAs)

Start date: September 2017

Dietary strategies promote chemoprevention. We have recently reported that levels of cytoskeletal proteins, keratins, are altered in the earliest stages of colon cancer and that this is modifiable by diet (1). Keratin status was modifiable by dietary fibre – representing a simple but cost-effective way to design interventions (diet, lifestyle and chemo-preventive) for improved gut function.
This cross disciplinary project (chemical engineering, nutrition, biomolecular science) is specifically directed to systems analysis to define, at molecular and physical scales, the impact of diet-derived short-chain fatty acids in the colon.

a) Develop functional screens for assessment of spatial and temporal protein acetylation and ubiquitination status at the cellular level using High Content Analysis (refs 2-4)
b) Develop methods for co-analysis of acetylation and ubiquitination by proteomic techniques including mass spectrometry (5)
c) Integrate the data for a systems model of the mode of action of short chain fatty acids at the molecular and cellular level.
d) Dietary fibre is fermented in the colon by the gut flora (microbiome), to produce short chain fatty acids that can act alone and in combination. Understanding the interplay of these compounds with cell physiology will optimise health care through evidence-based intervention, potentially via diet and lifestyle changes. The data will also contribute to effective diagnosis and patient-specific prediction by generating information of short chain fatty acid specific effect at the molecular and cellular level.