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School of Life Sciences
 

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Bill Wickstead

Associate Professor, Faculty of Medicine & Health Sciences

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Research Summary

My research interests include genome architecture, chromosome segregation, molecular motor function and multigene-family evolution. The uniting factor behind these topics is the importance they have… read more

Recent Publications

  • AWUAH-MENSAH, GEORGINA, MCDONALD, JENNIFER, STEKETEE, PIETER C, AUTHEMAN, DELPHINE, WHIPPLE, SARAH, D'ARCHIVIO, SIMON, BRANDT, CORDELIA, CLARE, SIMON, HARCOURT, KATHERINE, WRIGHT, GAVIN J, MORRISON, LIAM J, GADELHA, CATARINA and WICKSTEAD, BILL, 2021. PLoS Pathog. 17(1), e1009224
  • BRUSINI, LORENZO, D'ARCHIVIO, SIMON, MCDONALD, JENNIFER and WICKSTEAD, BILL, 2021. Frontiers in Cellular and Infection Microbiology. 11, 641174
  • DAVIES, CARYS, OOI, CHER-PHENG, SIOUTAS, GEORGIOS, HALL, BELINDA S, SIDHU, HANEESH, BUTTER, FALK, ALSFORD, SAM, WICKSTEAD, BILL and RUDENKO, GLORIA, 2021. Nucleic Acids Res. 49, 3242-3262
  • LEONARD, GUY, LABARRE, AUR锟絃IE, MILNER, DAVID S, MONIER, ADAM, SOANES, DARREN, WIDEMAN, JEREMY G, MAGUIRE, FINLAY, STEVENS, SAM, SAIN, DIVYA, GRAU-BOV锟�, XAVIER, SEB锟�-PEDR锟絊, ARNAU, STAJICH, JASON E, PASZKIEWICZ, KONRAD, BROWN, MATTHEW W, HALL, NEIL, WICKSTEAD, BILL and RICHARDS, THOMAS A, 2018. Open Biol. 8(1), 170184

Current Research

My research interests include genome architecture, chromosome segregation, molecular motor function and multigene-family evolution. The uniting factor behind these topics is the importance they have to understanding the biology of the parasite Trypanosoma brucei. Much of the research in the lab also integrates bioinformatic and mathematical tools with wet-bench work. The use of these tools - particularly in an age where so much genomic information is becoming available - can greatly speed-up biological research and help us to ask the right questions of the systems we study.

More information regarding the lab's research can be found at: .

African trypanosomes and antigenic variation

Trypanosoma brucei is a single-celled parasite of the blood which causes the disease "sleeping sickness" in humans. The disease kills ~50 000 annually in sub-Saharan regions and has been identified by the World Health Organisation as a neglected tropical disease. A related disease of cattle, n'gana, also has a major detrimental economic impact in some of Africa's poorest regions. The parasite is transmitted by the bite of the tsetse fly, and is unusual in parasitizing the bloodstream in an exclusively extracellular form - effectively in full view of the immune system. This feat is achieved by the parasite expressing a series of immunologically-distinct cell surface coats - a process known as antigenic variation. Trypanosome antigenic variation is an extreme version of a strategy of immune evasion used by a great number of parasites and pathogens (including malaria parasites, Giardia, Borrelia, Neisseria, and HIV), and understanding how trypanosomes achieve it is relevant to understanding other diseases as well as sleeping sickness itself.

Trypanosome antigenic variation

Genome architecture and segregation

The genome of T. brucei is highly adapted to the organism's lifestyle; around 20% of the entire genome sequence is dedicated to the process of antigenic variation. This includes a large number (~100) of linear minichromosomes, which serve as a reservoir for genes encoding cell surface proteins. At cell division, all of these chromosomes are segregated by the mitotic spindle with great fidelity. However, the chromosomes far out-number the spindle microtubules and the molecular details of this segregation mechanism are almost entirely unknown. The lab is currently working to discover the components of the mitotic machinery in trypanosomes and what features of the small chromosomes enable them to interact with the spindle. This will reveal how an essential part of the trypanosome cell functions and will also tell us about the evolution of mitosis in other organisms.

T.brucei karyotype

Molecular motors

The mitotic spindle is a specific part of the wider cytoskeleton - a system of filaments and molecular motors that is crucial for cell shape, division, movement and growth. There are three major classes of motor protein that move on the cytoskeleton of eukaryotes (that is, more complex non-bacterial organisms) - myosins, kinesins and dyneins. Only kinesins have thus-far been seen to be ubiquitously present in all eukaryotes, with losses of either all myosins or all dyneins from particular branches of the eukaryotic tree. All three motor classes are superfamilies of proteins encompassing multiple types with specific functions. The lab has worked extensively to characterize the types of motor found in cells and in this way has discovered "new" families of motors for which little functional data are available. Work in the lab is characterizing these families and also testing the function of unclassified motors in trypanosome growth and division.

Kinesin13 localisation

Evolution of the cell

Trypanosomes are unlike model organisms like yeast in several key ways. However, trypanosomes share a common ancestor with all other eukaryotes and the features of this lineage evolved from the same ancestral cell. With the advent of genome sequencing for increasing numbers of eukaryotes, it is becoming possible to compare the complete content of multiple organisms. In this way, we can make predictions about the functions performed by a specific organism, even when that function has not been directly observed. Moreover, by inferring the genomic content of the ancestors to particular lineages, it is possible to look back in time to "observe" long extinct cells in terms of their encoded biology. The lab is using these comparative genomic methods to reconstruct the evolution of key features of eukaryotic cells.

LECA

  • AWUAH-MENSAH, GEORGINA, MCDONALD, JENNIFER, STEKETEE, PIETER C, AUTHEMAN, DELPHINE, WHIPPLE, SARAH, D'ARCHIVIO, SIMON, BRANDT, CORDELIA, CLARE, SIMON, HARCOURT, KATHERINE, WRIGHT, GAVIN J, MORRISON, LIAM J, GADELHA, CATARINA and WICKSTEAD, BILL, 2021. PLoS Pathog. 17(1), e1009224
  • BRUSINI, LORENZO, D'ARCHIVIO, SIMON, MCDONALD, JENNIFER and WICKSTEAD, BILL, 2021. Frontiers in Cellular and Infection Microbiology. 11, 641174
  • DAVIES, CARYS, OOI, CHER-PHENG, SIOUTAS, GEORGIOS, HALL, BELINDA S, SIDHU, HANEESH, BUTTER, FALK, ALSFORD, SAM, WICKSTEAD, BILL and RUDENKO, GLORIA, 2021. Nucleic Acids Res. 49, 3242-3262
  • LEONARD, GUY, LABARRE, AUR锟絃IE, MILNER, DAVID S, MONIER, ADAM, SOANES, DARREN, WIDEMAN, JEREMY G, MAGUIRE, FINLAY, STEVENS, SAM, SAIN, DIVYA, GRAU-BOV锟�, XAVIER, SEB锟�-PEDR锟絊, ARNAU, STAJICH, JASON E, PASZKIEWICZ, KONRAD, BROWN, MATTHEW W, HALL, NEIL, WICKSTEAD, BILL and RICHARDS, THOMAS A, 2018. Open Biol. 8(1), 170184
  • ABBAS, ALI HADI, PEREIRA, SARA SILVA, D'ARCHIVIO, SIMON, WICKSTEAD, BILL, MORRISON, LIAM J., HALL, NEIL, HERTZ-FOWLER, CHRISTIANE, DARBY, ALISTAIR C. and JACKSON, ANDREW P., 2018. The Structure of a Conserved Telomeric Region Associated with Variant Antigen Loci in the Blood Parasite Trypanosoma congolense GENOME BIOLOGY AND EVOLUTION. 10(9), 2458-2473
  • PATEL JT, BELSHAM HR, RATHBONE AJ, WICKSTEAD B, GELL C and FRIEL CT, 2016. Open biology. 6(10),
  • D'ARCHIVIO S and WICKSTEAD B, 2016. The Journal of cell biology.
  • RACHEL, R.A., YAMAMOTO, E.A., DEWANJEE, M.K., MAY-SIMERA, H.L., SERGEEV, Y.V., HACKETT, A.N., POHIDA, K., MUNASINGHE, J., GOTOH, N., WICKSTEAD, B., FARISS, R.N., DONG, L., LI, T. and SWAROOP, A., 2015. Hum Mol Genet. 24(13), 3775-3791
  • ROQUES, M., WALL, R.J., DOUGLASS, A.P., RAMAPRASAD, A., FERGUSON, D.J., KAINDAMA, M.L., BRUSINI, L., JOSHI, N., RCHIAD, Z., BRADY, D., GUTTERY, D.S., WHEATLEY, S.P., YAMANO, H., HOLDER, A.A., PAIN, A., WICKSTEAD, B. and TEWARI, R., 2015. PLoS Pathog. 11(11), e1005273
  • GADELHA, C., ZHANG, W., CHAMBERLAIN, J.W., CHAIT, B.T., WICKSTEAD, B. and FIELD, M.C., 2015. Mol Cell Proteomics. 14(7), 1911-1926
  • GADELHA C, ZHANG W, CHAMBERLAIN JW, CHAIT BT, WICKSTEAD B and FIELD MC, 2015. Molecular & cellular proteomics : MCP. 14(7), 1911-26
  • STANNE TM, NARAYANAN MS, RIDEWOOD S, LING A, WITMER K, KUSHWAHA M, WIESLER S, WICKSTEAD B, WOOD J and RUDENKO G, 2015. The Journal of biological chemistry. 290(45), 26954-67
  • GUTTERY DS, POULIN B, RAMAPRASAD A, WALL RJ, FERGUSON DJP, BRADY D, PATZEWITZ E, WHIPPLE S, STRASCHIL U, WRIGHT MH, MOHAMED AMAH, RADHAKRISHNAN A, AROLD ST, TATE EW, HOLDER AA, WICKSTEAD B, PAIN A and TEWARI R, 2014. Cell host & microbe. 16(1), 128-40
  • CROSS GAM, KIM H and WICKSTEAD B, 2014. Molecular and biochemical parasitology. 195(1), 59-73
  • POULIN B, PATZEWITZ E, BRADY D, SILVIE O, WRIGHT MH, FERGUSON DJP, WALL RJ, WHIPPLE S, GUTTERY DS, TATE EW, WICKSTEAD B, HOLDER AA and TEWARI R, 2013. Biology open. 2(11), 1160-70
  • WHEELER RJ, SCHEUMANN N, WICKSTEAD B, GULL K and VAUGHAN S, 2013. Molecular microbiology. 90(6), 1339-55
  • DE LEON JC, SCHEUMANN N, BEATTY W, BECK JR, TRAN JQ, YAU C, BRADLEY PJ, GULL K, WICKSTEAD B and MORRISSETTE NS, 2013. Eukaryotic cell. 12(7), 1009-19
  • GUTTERY, D.S., POULIN, B., FERGUSON, D.J.P., SZ脰艕R, B., WICKSTEAD, B., CARROLL, P.L., RAMAKRISHNAN, C., BRADY, D., PATZEWITZ, E.-M., STRASCHIL, U., SOLYAKOV, L., GREEN, J.L., SINDEN, R.E., TOBIN, A.B., HOLDER, A.A. and TEWARI, R., 2012. PLOS Pathogens. 8(9), e1002948
  • DANIELS, J.P., GULL, K. and WICKSTEAD, B., 2012. Eukaryot Cell. 11(5), 662-672
  • HODGES, M.E., WICKSTEAD, B., GULL, K. and LANGDALE, J.A., 2012. New Phytol. 195(3), 526-540
  • SUNTER, J., WICKSTEAD, B., GULL, K. and CARRINGTON, M., 2012. PLoS One. 7(4), e35167
  • KELLY, S., WICKSTEAD, B. and GULL, K., 2011. Proceedings of the Royal Society. B, Biological Sciences. 278(1708), 1009-1018
  • WICKSTEAD, B. and GULL, K., 2011. Journal of Cell Biology. 194(4), 513-525
  • WICKSTEAD, BILL and GULL, KEITH, 2011. The evolutionary biology of dyneins. In: KING, STEPHEN, ed., Dyneins: Structure, biology and disease Academic Press. 88-121
  • HODGES, MATTHEW E, WICKSTEAD, BILL, GULL, KEITH and LANGDALE, JANE A, 2011. BMC Plant Biol. 11(1), 185
  • WICKSTEAD, BILL, CARRINGTON, JAMIE T, GLUENZ, EVA and GULL, KEITH, 2010. PloS one. 5(11), e15020
  • WICKSTEAD, B, GULL, K. and RICHARDS, T.A., 2010. BMC Evolutionary Biology. 10, 110
  • HODGES, M.E., SCHEUMANN, N., WICKSTEAD, B., LANGDALE, J.A. and GULL, K., 2010. Journal of Cell Science. 123(9), 1407-1413
  • DANIELS, JAN-PETER, GULL, KEITH and WICKSTEAD, BILL, 2010. Microbiology and molecular biology reviews : MMBR. 74(4), 552-69
  • DANIELS, JAN-PETER, KELLY, STEVEN, WICKSTEAD, BILL and GULL, KEITH, 2009. Biology direct. 4, 24
  • BARKER, AMY R, WICKSTEAD, BILL, GLUENZ, EVA and GULL, KEITH, 2008. Molecular and biochemical parasitology. 162(2), 112-22
  • UZUREAU, PIERRICK, DANIELS, JAN-PETER, WALGRAFFE, DAVID, WICKSTEAD, BILL, PAYS, ETIENNE, GULL, KEITH and VANHAMME, LUC, 2008. Molecular microbiology. 69(5), 1121-36
  • WICKSTEAD, BILL and GULL, KEITH, 2007. Dyneins across eukaryotes: a comparative genomic analysis. Traffic (Copenhagen, Denmark). 8(12), 1708-21
  • DEVAUX, SARA, KELLY, STEVEN, LECORDIER, LAURENCE, WICKSTEAD, BILL, PEREZ-MORGA, DAVID, PAYS, ETIENNE, VANHAMME, LUC and GULL, KEITH, 2007. Molecular biology of the cell. 18(4), 1293-301
  • GADELHA, CATARINA, WICKSTEAD, BILL and GULL, KEITH, 2007. Cell motility and the cytoskeleton. 64(8), 629-43
  • KELLY, STEVEN, REED, JENNY, KRAMER, SUSANNE, ELLIS, LOUISE, WEBB, HELENA, SUNTER, JACK, SALJE, JEANNE, MARINSEK, NINA, GULL, KEITH, WICKSTEAD, BILL and CARRINGTON, MARK, 2007. Molecular and biochemical parasitology. 154(1), 103-9
  • HAMMARTON, TANSY C, WICKSTEAD, BILL and MCKEAN, PAUL G, 2007. Cell structure, cell division and the cell cycle. In: BARRY, JOHN D, MCCULLOCH, RICHARD, MOTTRAM, JEREMY C and ACOSTA-SERRANO, A, eds., Trypanosomes: After the Genome Horizon Bioscience. 239-280
  • KELLY, S, SINGLETON, W, WICKSTEAD, B, ERSFELD, K and GULL, K, 2006. Eukaryotic cell. 5(5), 876-9
  • WICKSTEAD, BILL and GULL, KEITH, 2006. A "holistic" kinesin phylogeny reveals new kinesin families and predicts protein functions. Molecular biology of the cell. 17(4), 1734-43
  • GADELHA, CATARINA, WICKSTEAD, BILL, MCKEAN, PAUL G and GULL, KEITH, 2006. Journal of cell science. 119(Pt 12), 2405-13
  • KELLY, S, WICKSTEAD, B and GULL, K, 2005. An in silico analysis of trypanosomatid RNA polymerases: insights into their unusual transcription. Biochemical Society transactions. 33(Pt 6), 1435-7
  • BERRIMAN, MATTHEW, GHEDIN, ELODIE, HERTZ-FOWLER, CHRISTIANE, BLANDIN, GA脣LLE, RENAULD, HUBERT, BARTHOLOMEU, DANIELLA C, LENNARD, NICOLA J, CALER, ELISABET, HAMLIN, NANCY E, HAAS, BRIAN and B脰HM, 2005. The genome of the African trypanosome Trypanosoma brucei. Science (New York, N.Y.). 309(5733), 416-22
  • GADELHA, CATARINA, WICKSTEAD, BILL, DE SOUZA, WANDERLEY, GULL, KEITH and CUNHA-E-SILVA, NARCISA, 2005. Cryptic paraflagellar rod in endosymbiont-containing kinetoplastid protozoa. Eukaryotic cell. 4(3), 516-25
  • EL-SAYED, NAJIB M, MYLER, PETER J, BARTHOLOMEU, DANIELLA C, NILSSON, DANIEL, AGGARWAL, GAUTAM, TRAN, ANH-NHI, GHEDIN, ELODIE, WORTHEY, ELIZABETH A, DELCHER, ARTHUR L, BLANDIN, GA脣LLE and WESTENBERGE, 2005. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science (New York, N.Y.). 309(5733), 409-15
  • WICKSTEAD, BILL, ERSFELD, KLAUS and GULL, KEITH, 2004. The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes. Genome research. 14(6), 1014-24
  • VAUGHAN, SUE, WICKSTEAD, BILL, GULL, KEITH and ADDINALL, STEPHEN G, 2004. Molecular evolution of FtsZ protein sequences encoded within the genomes of archaea, bacteria, and eukaryota. Journal of molecular evolution. 58(1), 19-29
  • BECKER, MARION, AITCHESON, NIALL, BYLES, ELAINE, WICKSTEAD, BILL, LOUIS, EDWARD and RUDENKO, GLORIA, 2004. Isolation of the repertoire of VSG expression site containing telomeres of Trypanosoma brucei 427 using transformation-associated recombination in yeast. Genome research. 14(11), 2319-29
  • BRIGGS, LAURA J, DAVIDGE, JACQUELINE A, WICKSTEAD, BILL, GINGER, MICHAEL L and GULL, KEITH, 2004. More than one way to build a flagellum: comparative genomics of parasitic protozoa. Current biology : CB. 14(15), R611-2
  • WICKSTEAD, BILL, ERSFELD, KLAUS and GULL, KEITH, 2003. The mitotic stability of the minichromosomes of Trypanosoma brucei. Molecular and biochemical parasitology. 132(2), 97-100
  • WICKSTEAD, BILL, ERSFELD, KLAUS and GULL, KEITH, 2003. Repetitive elements in genomes of parasitic protozoa. Microbiology and molecular biology reviews : MMBR. 67(3), 360-75, table of contents
  • WICKSTEAD, BILL, ERSFELD, KLAUS and GULL, KEITH, 2003. The frequency of gene targeting in Trypanosoma brucei is independent of target site copy number. Nucleic acids research. 31(14), 3993-4000
  • ALSFORD, S, WICKSTEAD, B, ERSFELD, K and GULL, K, 2001. Molecular and biochemical parasitology. 113(1), 79-88
  • WICKSTEAD, B, GRIEVE, S M and WIMPERIS, S, 1998. Biophysical chemistry. 73(1-2), 129-36
  • TAYLOR, R M, WICKSTEAD, B, CRONIN, S and CALDECOTT, K W, 1998. Current biology : CB. 8(15), 877-80
  • KOUMANDOU VL, WICKSTEAD B, GINGER ML, VAN DER GIEZEN M, DACKS JB and FIELD MC, 1. Critical reviews in biochemistry and molecular biology. 48(4), 373-96
  • WICKSTEAD, BILL, ERSFELD, KLAUS and GULL, KEITH, Targeting of a tetracycline-inducible expression system to the transcriptionally silent minichromosomes of Trypanosoma brucei. Molecular and biochemical parasitology. 125(1-2), 211-6

School of Life Sciences

糖心原创
Medical School
Queen's Medical Centre
Nottingham NG7 2UH

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