Objective The research field of proteomics proceeds rapidly thanks to recent technological advances of instrumentation, methodology,and software development. Next Generation Proteomics (NGP) refers to the integration of these three areas to provide asystematic approach for measuring proteome dynamics in both time and space during various cellular responses. In thisproposal, I will analyze pre-ribosomal proteome dynamics in response to intracellular energy status using a NGP approach.Specifically, I will determine how cancer cells regulate Ribosome Biogenesis (RiBi) to aid their survival under conditions ofenergy deprivation, which frequently occurs in connection with solid tumour development. The host laboratory is well knownfor developing and applying NGP strategies and will provide me with training and access to all of the equipment andresources required. To carry out this project I will first optimise methods for purification of human pre-ribosomal particles,combining my existing knowledge of RiBi with expertise from the Lamond group in nucleolar isolation. I will then use aquantitative proteomics approach to analyze pre-ribosomes isolated from cells grown under conditions of varied glucosedeprivation. I will compare the components of pre-40S, pre-60S and pre-90S particles, respectively, using SILAC and thePepTracker software developed in the Lamond group. This project is based on my recent data showing that 47S pre-rRNAprocessing, which occurs in pre-90S particles, is suppressed by glucose deprivation in human adenocarcinoma HeLa andMCF7 cell lines. As the proteins contained in human pre-ribosomes are less well characterised than the correspondingyeast proteins, I will incorporate these results in a searchable database of human RiBi factors that will be freely available tothe community. As RiBi is the most energy-consuming process in eukaryotic cell the results of this project may lead to novelcancer treatment strategies which target deregulation of RiBi. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencescomputer and information sciencessoftwaresoftware developmentnatural sciencesbiological sciencesgeneticsRNAnatural scienceschemical sciencesanalytical chemistrymass spectrometry Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITY OF DUNDEE Net EU contribution € 195 454,80 Address Nethergate DD1 4HN Dundee United Kingdom See on map Region Scotland Eastern Scotland Angus and Dundee City Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80
