With next-generation sequencing and advances in mass spectrometry (MS) it is now possible to generate quantitative information for a biological system at many levels; transcriptome, translatome, proteome, metabolome and regulatory interactions via nucleotide binding proteins and protein interaction networks. Despite the advances in biomedical knowledge that genomic and post-genomic science has brought, much of the full complexity of biological function encoded in genomes is yet to be uncovered. A significant amount of functional complexity is brought about by the dynamic behaviour of the proteome, as a translated protein may be differentially and dynamically modified, may associate with different binding partners or traffic to different parts of a cell depending on the status of the cell.
In this project we will use state of the art high throughput quantitative proteomics methods coupled with multi protein complex isolation to chart the dynamic changes in the translatome and proteome upon lineage commitment of mouse embryonic stem cells. In this short rotation project we will look at the changes in protein components in complexes we have identified as important facilitators of the transition from an epistem cell like state to that of efficiently differentiated neuroectodermal and mesendodermal cells.
The project will involve stem cell culture, plus quantitative mass spectrometry, cell imaging and bioinformatic analysis.
The project will fit at the core of the group research activity of both the Lilley and Martinez Arias groups. The student will be supported and assisted by other members of these groups, including bioinformaticians, cell biologists and proteomics experts.
- A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells. Muñoz Descalzo S, Rué P, Faunes F, Hayward P, Jakt LM, Balayo T, Garcia-Ojalvo J, Martinez Arias A.Mol Syst Biol. 2013 Oct 8;9:694.
- The effect of organelle discovery upon sub-cellular protein localisation. Breckels LM, Gatto L, Christoforou A, Groen AJ, Lilley KS, Trotter MW.J Proteomics. 2013 Aug 2;88:129-40.
- In vivo analysis of proteomes and interactomes using Parallel Affinity Capture (iPAC) coupled to mass spectrometry. Rees JS, Lowe N, Armean IM, Roote J, Johnson G, Drummond E, Spriggs H, Ryder E, Russell S, St Johnston D, Lilley KS. Mol Cell Proteomics. 2011 Jun;10(6):