School of Life Sciences
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Utilising state-of-the-art technology such as genome editing and high throughput sequencing, research within our theme addresses the fundamental principles of cell biology, including:

  • genome biology
  • cell functions
  • signal transduction
  • stem cell specification
  • molecular mechanisms of diseases

Our research is supported through grants from the Wellcome Trust, MRC, BBSRC, EPSRC, BHF, EU, Royal Society, Charities and Industry.

Molecular-Cell-Biology-and-Development-466px

Molecular Cell Biology
and Development

 
 

Specific areas of interest

  • Genome biology including DNA repair and transposition, chromosome dynamics and organisation of the oocyte nucleus

  • Cell morphology, motor proteins and cytoskeletal dynamics

  • Signal transduction pathways regulating cellular responses

  • Gene regulatory networks determining cell fate

  • Evolution of pluripotency and primordial germ cell specification

  • Specification of embryonic and adult blood stem cells

  • Signal transduction pathways that modulate malaria parasite development and parasite-host interaction

  • Molecular mechanisms regulating heart formation and vascular biology

  • Molecular mechanisms underlying cardiovascular, bone, skeletal muscle and neurodegenerative diseases

  • Developmental biology utilising drosophila, zebrafish, xenopus, axolotl, chick and mouse model systems

 

Principal investigators

Dr Lynn Bedford

26S proteasome function in neurodegenerative diseases

Dr Ed Bolt

Chromosone dynamics and DNA repair

Professor Ronald Chalmers

Molecular mechanisms and biological consequences of DNA transposition

Dr Marios Georgiou

Cell morphogenesis

Dr Martin Gering

Haematopoietic stem cells

Professor Andrew Johnson

Germ cell specification

Dr Rob Layfield

Dysfunction of ubiquitin-mediated processes

Dr Lopa Leach

Vascular Biology

Dr Matt Loose

Gene regulatory networks

Dr Siobhan Loughna

Formation of the heart and vascular systems

Dr Andrew Renault

Development of the embryonic gonad and airway (tracheal) system in drosophila

Professor Fred Sablitzky
(Academic Lead)

Cell fate determination

Professor Peter Shaw

Elk-1 and STAT3 function in cell proliferation and cancer

Professor Rita Tewari

Signalling pathways modulating malaria parasite development

Dr Sally Wheatley

Cytoskeleton and cell morphology

 

Publications

2016
  • Alves E, Maluf FV, Bueno VB, Guido RV, Oliva G, Singh M, Scarpelli P, Costa F, Sartorello R, Catalani LH, Brady D, Tewari R, Garcia CR. Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2α) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum.
    Sci Rep. 2016, 6:22093. DOI: 10.1038/srep22093.

  • Brown LE, Middleton AM, King JR, Loose M.Multicellular Mathematical Modelling of Mesendoderm Formation in Amphibians.
    Bull Math Biol. 2016. DOI:10.1007/s11538-016-0150-8. PMID:26934886.

  • England J, Pang KL, Parnall M, Haig MI, Loughna S. Cardiac troponin T is necessary for normal development in the embryonic chick heart. Journal of Anatomy. 2016, (in press).

  • Majsec K, Bolt EL, Ivančić-Baće I.Cas3 is a limiting factor for CRISPR-Cas immunity in Escherichia coli cells lacking H-NS.
    BMC Microbiol. 2016, 16(1):28. DOI: 10.1186/s12866-016-0643-5. PMID:26956996.

  • Pakkiriswami S, Couto A, Nagarajan U, Georgiou M.Glycosylated Notch and Cancer.
    Front Oncol. 2016, 18;6:37. DOI: 10.3389/fonc.2016.00037. PMID:26925390.

  • Saxton J, Ferjentsik Z, Ducker C, Johnson AD, Shaw PE.Stepwise evolution of Elk-1 in early deuterostomes.
    FEBS J. 2016, 283(6):1025-38. DOI: 10.1111/febs.13607. PMID: 26613204.

  • Scott D, Garner TP, Long J, Strachan J, Mistry SC, Bottrill AR, Tooth DJ, Searle MS, Oldham NJ, Layfield R.Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin.
    Proteomics. 2016. DOI: 10.1002/pmic.201600067. PMID:27037516.

 
2015
  • Aljaberi AM, Webster JR, Wheatley SP.Mitotic activity of survivin is regulated by acetylation at K129.
    Cell Cycle. 2015, 14(11):1738-47. DOI: 10.1080/15384101.2015.1033597.
  • Andreadaki M, Mollenkopf HJ, Nika F, Brady D, Tewari R, Matuschewski K, Siden-Kiamos I.Global expression profiling reveals shared and distinct transcript signatures in arrested act2(-) and CDPK4(-) Plasmodium berghei gametocytes.
    Mol Biochem Parasitol. 2015, 201(2):100-7. DOI: 10.1016/j.molbiopara.2015.07.001. PMID:26222913.
  • Bolt EL, Jenkins T, Russo VM, Ahmed S, Cavey J, Cass SD.Identification of Escherichia coli ygaQ and rpmG as novel mitomycin C resistance factors implicated in DNA repair.
    Biosci Rep. 2015, 36(1). pii: e00290. DOI: 10.1042/BSR20150249. PMID:26704888.
  • Carter WG, Vigneswara V, Newlaczyl A, Wayne D, Ahmed B, Saddington S, Brewer C, Raut N, Gerdes HK, Erdozain AM, Tooth D, Bolt EL, Osna NA, Tuma DJ, Kharbanda KK.Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury.
    Biochem Biophys Res Commun. 2015, 458(3):626-31. DOI: 10.1016/j.bbrc.2015.01.158. PMID:25684186.
  • Cass SD, Haas KA, Stoll B, Alkhnbashi OS, Sharma K, Urlaub H, Backofen R, Marchfelder A, Bolt EL.The role of Cas8 in type I CRISPR interference.
    Biosci Rep. 2015, 35(3). pii: e00197. DOI: 10.1042/BSR20150043. PMID:26182359.
  • Ebrahim N, Leach L. Temporal studies into attachment, VE-cadherin perturbation and paracellular migration of human umbilical mesenchymal stem cells across umbilical vein endothelial monolayers.
    Stem Cells Dev. 2015, 24(4):426-36.
  • Eleftheriou M, Pascual AJ, Wheldon LM, Perry C, Abakir A, Arora A, Johnson AD, Auer DT, Ellis IO, Madhusudan S, Ruzov A.5-Carboxylcytosine levels are elevated in human breast cancers and gliomas.
    Clin Epigenetics. 2015, 7(1):88. DOI: 10.1186/s13148-015-0117-x. PMID:26300993.
  • Evans T, Loose M.AlignWise: a tool for identifying protein-coding sequence and correcting frame-shifts.
    BMC Bioinformatics. 2015,16:376. DOI: 10.1186/s12859-015-0813-8. PMID:26553107.
  • Goode A, Long JE, Shaw B, Ralston SH, Visconti MR, Gianfrancesco F, Esposito T, Gennari L, Merlotti D, Rendina D, Rea SL, Sultana M, Searle MS, Layfield R.Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function.
    Biochim Biophys Acta. 2014, 1842(7):992-1000. DOI: 10.1016/j.bbadis.2014.03.006. PMID:24642144.
  • Guttery DS, Roques M, Holder AA, Tewari R.Commit and Transmit: Molecular Players in Plasmodium Sexual Development and Zygote Differentiation.
    Trends Parasitol. 2015, 31(12):676-85. DOI: 10.1016/j.pt.2015.08.002. PMID:26440790.
  • Ip CL, Loose M, Tyson JR, de Cesare M, Brown BL, Jain M, Leggett RM, Eccles DA, Zalunin V, Urban JM, Piazza P, Bowden RJ, Paten B, Mwaigwisya S, Batty EM, Simpson JT, Snutch TP, Birney E, Buck D, Goodwin S, Jansen HJ, O'Grady J, Olsen HE; MinION Analysis and Reference Consortium. MinION Analysis and Reference Consortium: Phase 1 data release and analysis.
    F1000Res. 2015, 4:1075. DOI: 10.12688/f1000research.7201.1. PMID:26834992.
  • Ivančić-Baće I, Cass SD, Wearne SJ, Bolt EL.Different genome stability proteins underpin primed and naïve adaptation in E. coli CRISPR-Cas immunity.
    Nucleic Acids Res. 2015, 43(22):10821-30. DOI: 10.1093/nar/gkv1213. PMID: 26578567.
  • Johnson AD, Alberio R.Primordial germ cells: the first cell lineage or the last cells standing?
    Development. 2015, 15;142(16):2730-9. DOI: 10.1242/dev.113993. PMID: 26286941.
  • Khan GH, Galazis N, Docheva N, Layfield R, Atiomo W.Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration.
    Hum Reprod. 2015, 30(1):133-48. DOI: 10.1093/humrep/deu268. PMID:25351721.
  • Loman N, Goodwin S, Jansen H, Loose M.A disruptive sequencer meets disruptive publishing.
    F1000Res. 2015, 4:1074. DOI: 10.12688/f1000research.7229.1. PMID:26998227.
  • Loreto A, Di Stefano M, Gering M, Conforti L.Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca(2+) Influx but Only Modestly Influenced by Mitochondria.
    Cell Rep. 2015, 13(11):2539-52. DOI: 10.1016/j.celrep.2015.11.032. PMID: 26686637.
  • Majcher V, Goode A, James V, Layfield R.Autophagy receptor defects and ALS-FTLD.
    Mol Cell Neurosci. 2015, 66(Pt A):43-52. DOI: 10.1016/j.mcn.2015.01.002. PMID:25683489.
  • Rollie C, Schneider S, Brinkmann AS, Bolt EL, White MF.Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition.
    Elife. 2015, 18;4. DOI: 10.7554/eLife.08716. PMID: 26284603.
  • Roques M, Wall RJ, Douglass AP, Ramaprasad A, Ferguson DJ, Kaindama ML, Brusini L, Joshi N, Rchiad Z, Brady D, Guttery DS, Wheatley SP, Yamano H, Holder AA, Pain A, Wickstead B, Tewari R.Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.
    PLoS Pathog. 2015, 11(11):e1005273. DOI: 10.1371/journal.ppat.1005273. PMID: 26565797.
  • Safeukui I, Gomez ND, Adelani AA, Burte F, Afolabi NK, Akondy R, Velazquez P, Holder A, Tewari R, Buffet P, Brown BJ, Shokunbi WA, Olaleye D, Sodeinde O, Kazura J, Ahmed R, Mohandas N, Fernandez-Reyes D, Haldar K.Malaria induces anemia through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen.
    MBio. 2015, 6(1). pii: e02493-14. DOI: 10.1128/mBio.02493-14. PMID:25604792.
  • Scott D, Layfield R, Oldham NJ.Structural insights into interactions between ubiquitin specific protease 5 and its polyubiquitin substrates by mass spectrometry and ion mobility spectrometry.
    Protein Sci. 2015, 24(8):1257-63. DOI: 10.1002/pro.2692. PMID:25970461.
  • Scott D, Layfield R, Oldham NJ.Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5.
    Proteomics. 2015, 15(16):2835-41. DOI: 10.1002/pmic.201400457. PMID:25641936.
  • Scott D, Oldham NJ, Strachan J, Searle MS, Layfield R.Ubiquitin-binding domains: mechanisms of ubiquitin recognition and use as tools to investigate ubiquitin-modified proteomes.
    Proteomics. 2015,15(5-6):844-61, DOI: 10.1002/pmic.201400341. PMID:25327553.
  • Tellier, M., Claeys Bouuaert, C. & Chalmers, R. Mariner and the ITm family of transposons.
    Microbiology Spectrum. 2015, DOI: 10.1128/microbiolspec. MDNA3-0033-2014. PMID: 26104691
  • Wheatley SP.The functional repertoire of survivin's tails.
    Cell Cycle. 2015, 14(2):261-8. DOI: 10.4161/15384101.2014.979680. PMID:25607650.
  • Yusuf NA, Green JL, Wall RJ, Knuepfer E, Moon RW, Schulte-Huxel C, Stanway RR, Martin SR, Howell SA, Douse CH, Cota E, Tate EW, Tewari R, Holder AA.The Plasmodium Class XIV Myosin, MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain.
    J Biol Chem. 2015, 290(19):12147-64. DOI: 10.1074/jbc.M115.637694. PMID:25802338.
 
2014
  • Aljaberi AM, Webster JR, Wheatley SP.Analysis of the functional repertoire of a mutant form of survivin, K129E, which has been linked to lung cancer.
    Cancer Cell Int. 2014, 14:78. DOI: 10.1186/s12935-014-0078-8. PMID:25788861.
  • Bouuaert CC, Tellier M, Chalmers R.One to rule them all: A highly conserved motif in mariner transposase controls multiple steps of transposition.
    Mob Genet Elements. 2014, 4(1):e28807. PMID:24812590.
  • Brown LE, King JR, Loose M.Two different network topologies yield bistability in models of mesoderm and anterior mesendoderm specification in amphibians.
    J Theor Biol. 2014, 353:67-77. DOI: 10.1016/j.jtbi.2014.03.015. PMID:24650939.
  • Brown WR, Thomas G, Lee NC, Blythe M, Liti G, Warringer J, Loose MW.Kinetochore assembly and heterochromatin formation occur autonomously in Schizosaccharomyces pombe.
    Proc Natl Acad Sci U S A. 2014, 111(5):1903-8. DOI: 10.1073/pnas.1216934111. PMID:24449889.
  • Chatfield J, O'reilly M, Bachvarova RF, Ferjentsik Z, Redwood C, Walmsley M, Patient R, Loose M and Johnson AD. Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos.
    Development. 2014, 141(12), 2429-40. DOI: 10.1242/dev.105346.
  • Chen WC, Pauls S, Bacha J, Elgar G, Loose M, Shimeld SM.Dissection of a Ciona regulatory element reveals complexity of cross-species enhancer activity.
    Dev Biol. 2014, 390(2):261-72. DOI: 10.1016/j.ydbio.2014.03.013. PMID:24680932.
  • Claeys Bouuaert, C., Walker, N., Liu, D. & Chalmers, R. Crosstalk between transposase subunits during cleavage of the mariner transposon.
    Nucleic Acids Res. 2014, 42, 5799-5808. DOI: 10.1093/nar/gku172. PMID: 24623810.
  • Erdozain AM, Morentin B, Bedford L, King E, Tooth D, Brewer C, Wayne D, Johnson L, Gerdes HK, Wigmore P, Callado LF, Carter WG.Alcohol-related brain damage in humans.
    PLoS One. 2014 Apr 3;9(4):e93586. DOI: 10.1371/journal.pone.0093586. PMID:24699688.
  • Evans T, Wade CM, Chapman FA, Johnson AD, Loose M. Acquisition of germ plasm accelerates vertebrate evolution.
    Science. 2014, 344(6180):200-3. DOI: 10.1126/science.1249325. PMID: 24723612.
  • Ferguson DJ, Balaban AE, Patzewitz EM, Wall RJ, Hopp CS, Poulin B, Mohmmed A, Malhotra P, Coppi A, Sinnis P, Tewari R.The repeat region of the circumsporozoite protein is critical for sporozoite formation and maturation in Plasmodium.
    PLoS One. 2014, 9(12):e113923. DOI: 10.1371/journal.pone.0113923. PMID:25438048.
  • Frankenberg SR, Frank D, Harland R, Johnson AD, Nichols J, Niwa H, Schöler HR, Tanaka E, Wylie C, Brickman JM.The POU-er of gene nomenclature.
    Development. 2014, 141(15):2921-3. DOI: 10.1242/dev.108407. PMID:25053425.
  • Gong B, Shin M, Sun J, Jung CH, Bolt EL, van der Oost J, Kim JS.Molecular insights into DNA interference by CRISPR-associated nuclease-helicase Cas3.
    Proc Natl Acad Sci U S A. 2014, 111(46):16359-64. DOI: 10.1073/pnas.1410806111. PMID: 25368186.
  • Guttery DS, Poulin B, Ramaprasad A, Wall RJ, Ferguson DJ, Brady D, Patzewitz EM, Whipple S, Straschil U, Wright MH, Mohamed AM, Radhakrishnan A, Arold ST, Tate EW, Holder AA, Wickstead B, Pain A, Tewari R.Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.
    Cell Host Microbe. 2014, 16(1):128-40. DOI: 10.1016/j.chom.2014.05.020. PMID: 25011111.
  • Haack T, Schneider M, Schwendele B, Renault AD.Drosophila heart cell movement to the midline occurs through both cell autonomous migration and dorsal closure.
    Dev Biol. 2014, 396(2):169-82. DOI: 10.1016/j.ydbio.2014.08.033. 
  • Haoula Z, Shaw B, Daykin C, Hodgman C, Layfield R, Atiomo W.Validation of proteomic biomarkers previously found to be differentially expressed in women with polycystic ovary syndrome: a cross-sectional study.
    Gynecol Endocrinol. 2014, 30(3):213-6. DOI: 10.3109/09513590.2013.871520. PMID:24397393.
  • Kageyama S, Sou YS, Uemura T, Kametaka S, Saito T, Ishimura R, Kouno T, Bedford L, Mayer RJ, Lee MS, Yamamoto M, Waguri S, Tanaka K, Komatsu M. Proteasome dysfunction activates autophagy and the keap1-nrf2 pathway.
    J Biol Chem. 2014, 289(36):24944-55. DOI: 10.1074/jbc.M114.580357. PMID: 25049227.
  • Liu, D. & Chalmers, R. Hyper-active mariner transposons are created by mutations that disrupt allosterism and increase the rate of transposon end synapsis.
    Nucleic Acids Res. 2014, 42, 2637 – 2645. DOI:10.1093/nar/gkt1218. PMID: 24319144.
  • Liu YR, Laghari ZA, Novoa CA, Hughes J, Webster JR, Goodwin PE, Wheatley SP, Scotting PJ.Sox2 acts as a transcriptional repressor in neural stem cells.
    BMC Neurosci. 2014,15:95. DOI: 10.1186/1471-2202-15-95. PMID:25103589.
  • Mack NA, Georgiou M.The interdependence of the Rho GTPases and apicobasal cell polarity.
    Small GTPases. 2014, 5(2):10. DOI: 10.4161/21541248.2014.973768. PMID: 25469537.
  • Rea SL, Majcher V, Searle MS, Layfield R.SQSTM1 mutations--bridging Paget disease of bone and ALS/FTLD.
    Exp Cell Res. 2014, 325(1):27-37. DOI: 10.1016/j.yexcr.2014.01.020. PMID:24486447.
  • Shapiro IM, Layfield R, Lotz M, Settembre C, Whitehouse C.Boning up on autophagy: the role of autophagy in skeletal biology.
    Autophagy. 2014, 10(1):7-19. DOI: 10.4161/auto.26679. PMID:24225636.
  • Tewari R, Patzewitz EM, Poulin B, Stewart L, Baker DA.Development of a transgenic Plasmodium berghei line (Pb pfpkg) expressing the P. falciparum cGMP-dependent protein kinase, a novel antimalarial drug target.
    PLoS One. 2014, 9(5):e96923. DOI: 10.1371/journal.pone.0096923. PMID:24805991.
  • Tooth D, Garsed K, Singh G, Marciani L, Lam C, Fordham I, Fields A, Banwait R, Lingaya M, Layfield R, Hastings M, Whorwell P, Spiller R.Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit.
    Gut. 2014, 63(5):753-60. DOI: 10.1136/gutjnl-2012-304042. PMID:23911555.
  • Tripathy R, Kunwar PS, Sano H, Renault AD.Transcriptional regulation of Drosophila gonad formation.
    Dev Biol. 2014, 392(2):193-208. DOI: 10.1016/j.ydbio.2014.05.026. PMID:24927896.
  • Wheldon LM, Abakir A, Ferjentsik Z, Dudnakova T, Strohbuecker S, Christie D, Dai N, Guan S, Foster JM, Corrêa IR Jr, Loose M, Dixon JE, Sottile V, Johnson AD, Ruzov A.Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells.
    Cell Rep. 2014, 7(5):1353-61. DOI: 10.1016/j.celrep.2014.05.003. PMID:24882006.
  • Wright MH, Clough B, Rackham MD, Rangachari K, Brannigan JA, Grainger M, Moss DK, Bottrill AR, Heal WP, Broncel M, Serwa RA, Brady D, Mann DJ, Leatherbarrow RJ, Tewari R, Wilkinson AJ, Holder AA, Tate EW.Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.
    Nat Chem. 2014, 6(2):112-21. DOI: 10.1038/nchem.1830. PMID:24451586.
 

 

 

School of Life Sciences

University of Nottingham
Medical School
Queen's Medical Centre
Nottingham NG7 2UH

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