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Next Generation Proteomic Analysis of Pre-Ribosomal Proteome Dynamics Coupled to Glucose Metabolism in Caner Cells

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 a
systematic approach for measuring proteome dynamics in both time and space during various cellular responses. In this
proposal, 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 of
energy deprivation, which frequently occurs in connection with solid tumour development. The host laboratory is well known
for developing and applying NGP strategies and will provide me with training and access to all of the equipment and
resources 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 a
quantitative proteomics approach to analyze pre-ribosomes isolated from cells grown under conditions of varied glucose
deprivation. I will compare the components of pre-40S, pre-60S and pre-90S particles, respectively, using SILAC and the
PepTracker software developed in the Lamond group. This project is based on my recent data showing that 47S pre-rRNA
processing, which occurs in pre-90S particles, is suppressed by glucose deprivation in human adenocarcinoma HeLa and
MCF7 cell lines. As the proteins contained in human pre-ribosomes are less well characterised than the corresponding
yeast proteins, I will incorporate these results in a searchable database of human RiBi factors that will be freely available to
the community. As RiBi is the most energy-consuming process in eukaryotic cell the results of this project may lead to novel
cancer treatment strategies which target deregulation of RiBi.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2014

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Coordinator

UNIVERSITY OF DUNDEE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 195 454,80
Address
Nethergate
DD1 4HN Dundee
United Kingdom

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Region
Scotland Eastern Scotland Angus and Dundee City
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 195 454,80
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