University of Dundee

Professor Angus Lamond FRS FRSE FMedSci

Nuclear structure proteomics and gene expression
Position: 
Professor of Biochemistry
Address: 
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 385473, int ext 85473
Email: 

Research

We are studying gene expression, RNA processing and disease mechanisms in human cells and model organisms. Our goal is to characterise structure/function relationships within the cell and to study protein dynamics at a systems level. We do this using a combination of quantitative techniques, including mass-spectrometry-based proteomics, cell and molecular biology, fluorescence microscopy and computational approaches for big data analytics and interactive data exploration.

The use of high throughput proteomics technologies provides a system-wide approach allowing us to measure cellular responses for a large number of proteins in parallel. An integral part of this work is the development of new software tools for the management analysis and visualisation of complex proteomics data sets (see http://www.peptracker.com/).

To increase the value of the comprehensive proteomic data sets we have generated, we have incorporated all of our data into an open access, searchable online database, the Encyclopedia of Proteome Dynamics {Brenes:2017vl} (EPD; www.peptracker.com/epd). The EPD provides multiple interactive visualisations, allowing for convenient searching and interactive exploration of all the processed proteomics data. It also provides links to download both the processed data and associated raw MS files, the latter having been deposited in the ProteomeXchange PRIDE repository. The data visualisations in the EPD can be explored by clicking on selected data points, which reveals tooltips providing additional information and links to other related online data resources. Further, using the accompanying Search Box, each data visualization can be searched using multiple selectable criteria, including either proteins/genes of interest, GO terms, subunits of specific protein complexes or relation to functional pathways. Identified components can be readily highlighted and the resulting annoted visualization also downloaded and saved as an editable .svg file. For more detailed descriptions of the functionality and use of the EPD, see Brenes et al., 2017.

In our recent studies we have used combined proteomics, cell biology, microscopy and biochemical approaches in projects including, (i) to characterize the regulation of gene expression during physiological cell cycle progression (ii) to characterize human iPS cells and study genetic variation in the human population, (iii) to study proteome remodeling when healthy human cells are transformed into cancer cells by oncogene activation and (iv) we have used nematodes to study how gene and protein expression responds to acute starvation. In addition, we have studied biochemical mechanisms involved in pre-mRNA processing and alternative RNA splicing and have identified novel small molecule modulators of alternative splicing. For further information on these studies see; www.LamondLab.com

Publications

 “The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells” Endo, A., Ly, T., Pippa, R., Bensaddek, D., Nicolas, A. and Lamond A.I. J Biol Chem. (2017) 292(1):172-184.  doi: 10.1074/jbc.M116.751024.  PMID: 27872192 / PMCID: PMC5217677 view paper

“Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation” Hiraga, S.I., Ly, T., Hořejší, Z., Ohkubo, Y.N., Endo, A., Obuse, C., Boulton, S.J., Lamond, A.I. and Donaldson, A.D. EMBO Rep. (2017) pii: e201641983. doi: 10.15252/embr.201641983. PMID: 28077461 /  PMCID:PMC5331243 view paper

“Common genetic variation drives molecular heterogeneity in human iPSCs”  Kilpinen, H., Goncalves, A., Leha, A., Afzal, V., Alasoo, K., Ashford, S., Bala, S., Bensaddek, D., Casale, F.P., Culley, O.J., Danecek, P., Faulconbridge, A., Harrison, P.W., Kathuria, A., McCarthy, D., McCarthy,S.A., Meleckyte, R., Memari, Y., Moens, N., Soares, F., Mann, A., Streeter, I., Agu, C.A., Alderton, A., Nelson, R., Harper, S., Patel, M., White, A., Patel, S.R., Clarke, L., Halai, R., Kirton, C.M., Kolb-Kokocinski, A., Beales, P., Birney, E., Danovi, D., Lamond, A.I., Ouwehand, W.H., Vallier, L., Watt, F.M., Durbin, R., Stegle, O. and Gaffney, D.J.  Nature (2017) 546(7658):370-375 doi: 10.1038/nature22403. PMID: 28489815 / PMCID: PMC5524171 view paper

“Brd4-Brd2 isoform switching co-ordinates pluripotent exit with Smad2-dependent lineage specification” Fernandez-Alonso, R., Davidson, L., Hukelmann, J., Zengerle, M., Prescott, A.R., Lamond, A., Ciulli, A., Sapkota, G.P. and Findlay, G.M.  EMBO reports (2017) 18(7):1108-1122 doi: 10.15252/embr.201643534. PMID:28588073 / PMCID:PMC5494510 view paper

“Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans”; Harvald, E.B., Sprenger, R.R., Brændgaard Dall, K., Ejsing, C.S., Nielson, R., Mandrup, S., Brenes Murillo, A., Larance, M., Gartner, A., Lamond, A.I. and Faergeman, N.J. Cell Systems. (2017) 5(1):38-52.e4. doi: 10.1016/j.cels.2017.06.004. PMID:28734827

“The Helicase Aquarius/EMB-4 is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription”; Akay, A., Di Domenico, T., Suen, K.M., Nabih, A., Parada, G.E., Larance, M., Medhi, R., Berkyurek, A.C., Zhang, X., Wedeles, C.J., Rudolph, K.L.M., Engelhardt, J., Hemberg, M., Ma, P., Lamond, A.I., Claycomb, J.M. and Miska, E.A. Dev Cell. (2017)  42(3):241-255.e6. doi 10.1016/j.devcel.2017.07.002.  PMID:28787591 / PMCID:PMC5554785 view paper

“New Apex in Proteome Analysis”; Ly, T. and Lamond, A.I. Cell Systems (2017) 4(6):581-582. doi 10.1016/j.cels.2017.06.009. PMID:28662382

“Comparative genetic, proteomic and phosphoproteomic analysis of C.elegans embryos with a focus on ham-1/STOX and pig-1/MELK in dopaminergic neuron development”; Offenburger, S.L., Bensaddek, D., Murillo, A.B., Lamond, A.I. and Gartner, A. Sci Rep. (2017) 7(1):4314. doi 10.1038/s41598—017-04375-4. PMID:28659600 / PMCID:PMC5489525 view paper

“Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs”; Kilpinen, H., Goncalves, A., Leha, A., Afzal, V., Alasoo, K., Ashford, S., Bala, S., Bensaddek, D., Casale, F.P., Culley, O.J., Danecek, P., Faulconbridge, A., Harrison, P.W., Kathuria, A., McCarthy, D., McCarthy, S.A., Meleckyte, R., Memari, Y., Moens, N., Soares, F., Mann, A., Streeter, I., Agu, C.A., Alderton, A., Nelson, R., Harper, S., Patel, M., White, A., Patel, S.R., Clarke, L., Halai, R., Kirton, C.M., Kolb-Kokocinski, A., Beales, P., Birney, E., Danovi, D., Lamond, A.I., Ouwehand, W.H., Vallier, L., Watt, F.M., Durbin, R., Stegle, O. and Gaffney, D.J. Nature (2017) doi 10.1038/nature23012. PMID:28614302 view paper

“The Encyclopedia of Proteome Dynamics: a big data ecosystem for (prote)omics”; Brenes, A., Afzal, V., Kent, R. and Lamond A.I.  Nucleic Acid Research. (2017) doi:10.1093/nar/gkx807. PMID:28981707 / PMCID: PMC5753345 view paper

“Characterisation of the biflavonoid hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP”; Pawellek, A., Ryder, U., Tammsalu, T., King, L.J., Kreinin, H., Ly, T., Hay, R.T., Hartley, R. and Lamond, A.I. eLife (2017) 6:e27402. doi: 10.7554/eLife.27402. PMID:28884683 / PMCID: PMC5619949 view paper

“Prediction of Protein Complexes in Trypanosoma brucei by Protein Correlation Profiling Mass Spectrometry and Machine Learning”; Crozier, T.W.M., Tinti, M., Larance, M., Lamond, A.I. and Ferguson, M.A.J. Mol Cell Proteomics (2017) 16(12):2254-2267. Doi:10.1074/mcp.0117.068122. PMID:29042480 / PMCID:PMC5724185 view paper

“A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis”; Mishra, A., Oulès, B., Pisco, A.O., Ly, T., Liakath-Ali, K., Walko, G., Viswanathan, P., Tihy, M., Nijjher, J., Dunn, S.J., Lamond, A.I. and Watt, F.M. eLife (2017) doi:10.7554/eLife.27356. PMID:29043977 / PMCID:PMC5667932 view paper

“Proteomic analysis of cell cycle progression in asynchronous cultures, including mitotic subphases, using PRIMMUS”; Ly, T., Whigham, A., Clarke, R., Brenes-Murillo, A.J., Estes, B., Madhessian, D., Lundberg, E., Wadsworth, P. and Lamond A.I. eLife (2017) doi:10.7554/eLife.27574. PMID:29052541 / PMCID:PMC5650473 view paper

“Self-oligomerization regulates stability of Survival Motor Neuron (SMN) protein isoforms by sequestering an SCFSlmb degron”; Gray, K.M., Kaifer, K.A., Baillat, D., Wen, Y., Bonacci, T.R., Ebert, A.D., Raimer, A.C., Spring, A.M., Have S.T., Glascock, J.J., Gupta, K., Van Duyne, G.D., Emanuele, M.J.,Lamond, A.I., Wagner, E.J., Lorson, C.L. and Matera, A.G. Mol Biol Cell (2017) doi:10.1091/mbc.E17-11-0627. PMID: 29167380 view paper

“The cytotoxic T cell proteome and its shaping by the kinase mTOR”  Hukelmann, J.L., Anderson, K.E., Sinclair, L.V., Katarzyna, M.G., Brenes Murillo, A., Hawkins, P.T., Stephens, L.R., Lamond, A.I. and Cantrell, D.A.  Nature Immunology (2016) 17(1):104-12. doi: 10.1038/ni.3314. PMID:26551880 / PMCID: PMC4685757  view paper

“CDK-dependent phosphorylation of PHD1 on serine 130 alters its substrate preference in cells” Ortmann, B., Bensaddek, D., Carvalhal, S., Moser, S.C., Mudie, S., Griffis, E.R., Swedlow, J.R., Lamond, A.I. and Rocha, S. Journal of Cell Science (2016) Jan 1;129(1):191-205. doi: 10.1242/jcs.179911. PMID:26644182 / PMCID:PMC4732302 view paper

“The histone chaperone Vps75 forms multiple oligomeric assemblies capable of mediating exchange between histone H3-H4 tetramers and Asf1-H3-H4 complexes” Hammond, C., Sundaramoorthy, R., Larance, M., Lamond, A., Stevens, M.A., El-Mkami, H., Norman, D.G. and Owen-Hughes, T. Nucleic Acids Research (2016) Apr 2016, 44(13):6157-6172] doi: 10.1093/nar/gkw209  PMID:27036862 / PMCID: PMC5291247 view paper

“Global Membrane Protein Interactome Analysis using In vivo Crosslinking and MS-based Protein Correlation Profiling” Larance, M., Kirkwood, K.J., Tinti, M., Brenes Murillo, A., Ferguson, M.A.J. and Lamond, A.I. Molecular and Cellular Proteomics (2016) 15(7):2476-90. doi: 10.1074/mcp.O115.055467. PMID:27114452 / PMCID:PMC4937518 view paper

"Enhanced snoMEN vectors facilitate establishment of GFP-HIF-1a protein replacement human cell lines"; Ono, M., Yamada, K., Bensaddek, D., Afzal, V., Biddlestone, J., Ortmann, B., Mudie, S., Boivin, V., Scott, M.S., Rocha, S. and Lamond A.I.  PLOS ONE (2016) Apr 29;11(4):e0154759. doi: 10.1371/journal.pone.0154759 PMID: 27128805 / PMCID: PMC4851398 view paper

“Deep proteome analysis identifies new age-related processes in C.elegans” Narayan, V., Ly, T., Pourkarimi, E., Murillo, A.B., Gartner, A., Lamond, A.I. and Kenyon, C.  Cell Systems (2016) 3(2):144-59. doi: 10.1016/j.cels.2016.06.011.  PMID 27453442 / PMCID:PMC5003814 view paper