Introduction
 The study of changes in the cellular protein content is called proteomics. In diseases such as cancer, diabetes or cardiovascular disease, the expression of proteins or their post-translational modification (PTM) can lead to changes in the activity of proteins and enzymes. These activity changes can be markers of a particular disease and quantifying them by proteomic technologies is a major challenge. In my group, we are particularly interested in changes in PTMs such as phosphorylation. Protein phosphorylation is regulated in human cells by some five hundred protein kinases (enzymes that add phosphate to serine, threonine or tyrosine residues) and over one hundred protein phosphatases (enzymes that remove phosphate from serine, threonine or tyrosine residues). This PTM is highly dynamic and to quantify the changes at individual phosphorylation sites we use quantitative proteomics methods using high mass accuracy mass spectrometers.
If protein expression or protein PTMs are modulated this can lead to changes in enzyme activity. This in turn can lead to changes in metabolites in the cell, such as those involved in glycolysis, gluconogenesis or lipolysis. Quantitative mass spectrometry can again be used to measure these changes and this technique is called metabonomics. We are in the process of setting up mass spectrometry systems to analyse the metabolites from cancer biopsies as well as mouse models of cancer. With these techniques in place we should be able to gain an insight into the metabolic changes in cancer cells compared to healthy cells and then monitor the impact of anti-cancer drugs on the metabolome of cancer cells.
Email:
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
Lab Report
 Scientific Report 2010 Morrice
Key Publications
Yan L, Mieulet V, Burgess D, Findlay GM, Sully K, Procter J, Goris J,
Janssens V, Morrice NA, Lamb RF (2010). PP2A T61 epsilon is an
inhibitor of MAP4K3 in nutrient signaling to mTOR. Mol Cell 37, 633-42.
von Kriegsheim A, Baiocchi D, Birtwistle M, Sumpton D, Bienvenut W,
Morrice N, Yamada K, Lamond A, Kalna G, Orton R, Gilbert D, Kolch W
(2009). Cell fate decisions are specified by the dynamic ERK
interactome. Nat Cell Biol. 11, 1458-64.
Dubois F, Vandermoere F, Gernez A, Murphy J, Toth R, Chen S, Geraghty
KM, Morrice NA, MacKintosh C (2009). Differential 14-3-3 affinity
capture reveals new downstream targets of phosphatidylinositol 3-kinase
signalling. Mol Cell Proteomics 8, 2487-99.
Trinkle-Mulcahy L, Boulon S, Lam YW, Urcia R, Boisvert FM, Vandermoere
F, Morrice NA, Swift S, Rothbauer U, Leonhardt H, Lamond A (2008).
Identifying specific protein interaction partners using quantitative
mass spectrometry and bead proteomes.
J Cell Biol. 183, 223-39.
Elderkin S, Maertens GN, Endoh M, Mallery DL, Morrice N, Koseki H,
Peters G, Brockdorff N, Hiom K (2007). A phosphorylated form of Mel-18
targets the Ring1B histone H2A ubiquitin ligase to chromatin. Mol Cell
28, 107-20.
Williamson BL, Marchese J, Morrice N (2006). Automated Identification and Quantification of Protein Phosphorylation Sites by LC/MS on a Hybrid Triple Quadrupole Linear Ion Trap Mass Spectrometer. Mol Cell Proteomics 5, 337-46.
Biography
Education and qualifications
1987: PhD, University of London, Supervisor Alastair Aitken
1983: MSc in Analytical Chemistry, University of Bristol
1982: BSc, Chemistry (Second Class Honours), University of Bristol
Appointments
2010-present: Head of Proteomics, Beatson Institute for Cancer Research
2002-2010: Group Leader and Head of Proteomics, MRCPPU, University of Dundee
1994-2002: Senior Support Scientist, MRCPPU, University of Dundee
1987-1994: Postdoctoral Research Assistant, La Trobe University and Melbourne University, Australia
Recent Publications
Yan L, Mieulet V, Burgess D, Findlay GM, Sully K, Procter J, Goris J, Janssens V, Morrice NA, Lamb RF (2010). PP2A T61 epsilon is an inhibitor of MAP4K3 in nutrient signaling to mTOR. Mol Cell 37, 633-42.
Blomster HA, Imanishi SY, Siimes J, Kastu J, Morrice NA, Eriksson JE, Sistonen L (2010). In vivo identification of sumoylation sites by a signature tag and cysteine-targeted affinity purification. J Biol Chem. 285, 19324-9.
Nichols RJ, Dzamko N, Morrice NA, Campbell DG, Deak M, Ordureau A, Macartney T, Tong Y, Shen J, Prescott AR, Alessi DR (2010). 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. Biochem J. 430, 393-404.
Martin DM, Nett IR, Vandermoere F, Barber JD, Morrice NA, Ferguson MA (2010). Prophossi: automating expert validation of phosphopeptide-spectrum matches from tandem mass spectrometry. Bioinformatics 26, 2153-9.
Pozo-Guisado E, Campbell DG, Deak M, Alvarez-Barrientos A, Morrice NA, Alvarez IS, Alessi DR, Martín-Romero FJ (2010). Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry. J Cell Sci. 123, 3084-93.
Peirce MJ, Brook M, Morrice N, Snelgrove R, Begum S, Lanfrancotti A, Notley C, Hussell T, Cope AP, Wait R (2010). Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production. PLoS One 5, e11465.
Dunne A, Carpenter S, Brikos C, Gray P, Strelow A, Wesche H, Morrice N, O'Neill LA (2010). IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal). J Biol Chem. 285, 18276-82.
Lewis AE, Sommer L, Arntzen MO, Strahm Y, Morrice NA, Divecha N, D'Santos CS (2010). Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction. Mol Cell Proteomics, in press.
Lab Members
Scientific Officers: Sergio Lilla, David Sumpton
|
