Marcelo Rodrigues, Mr.

RABBIT PhD student (SFRH/BD/52537/2014)

“NAD metabolome and biomarkers in normal and Breast Cancer Cells: measuring chang" (2014-2018)

We propose to develop a set of techniques that will allow the intracellular concentration of NAD and of its metabolites to be determined and correlated to biomarkers identified in metabolism-driven diseases. This will be achieved through synthesis of NAD molecular probes (NAD-MPs) which are isotopically labelled entities for use in supplementation studies. These tools will then be used to investigate the quantitative incidence of NAD metabolism on biomarkers of angiogenesis and DNA repair. A large body of evidence, supported by animal models, demonstrates that the dietary supplementation of NAD metabolites causes substantial physiological relief in mammals suffering from age-related conditions linked to high fat diet and sedentary life styles. In addition to controlling the DNA repair process, the resulting increased intracellular NAD availability was shown to play a critical role in at least two major epigenetic protein modification mechanisms in a pathway, concentration and organelle dependent manner. The precise mechanisms for such outcomes remain poorly understood as the quantitation of the individual NAD metabolites and cellular distribution remains elusive whilst recognised as being critical to cellular ageing and disease development. There is a need for innovative approaches for measuring the concentration and location of NAD related analytes. These will help unravel the mechanisms by which dietary NAD metabolite supplementation influences the life of a cell.