The Lieschke group studies the haemopoietic system and leukocytes. The haemopoietic system is a collection of organs and tissues (bone marrow, spleen, lymph nodes etc.) responsible for the production of blood cells. Leukocytes (white blood cells) are the keys cells that defend the body against foreign substances. They also play a major role in determining whether tissue repairs and regenerates rather than scars after injury.

Research

Using the zebrafish as a model organism, the Lieschke group study blood cell development and function. They look at mutant zebrafish with faulty blood cell development to find insights into the genes that regulate the haemopoietic system. Mutant zebrafish also assist with understanding the role of leukocytes in inflammation and healing. Infection models that stimulate leukocytes in action are used to investigate the host-pathogen response.

Group Members

Research Themes

  • Discovery of genes critical for white blood cell development
  • How the inflammatory response is regulated
  • How modulating the inflammatory white blood cells might tip the outcome to favour regeneration rather than scarring
  • Investigating how white blood cells keep out and contain micro-organisms.

Featured Publications

Authors Title Published In
Payne JAE, Tailhades J, Ellett F, Kostoulias X, Fulcher AJ, Fu T, Leung R, Louch S, Tran A, Weber SA, Schittenhelm RB, Lieschke GJ, Qin CH, Irima D, Peleg AY, Cryle MJ.

Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus.

Nat Commun. 2021 Oct 25;12(1):6157. doi: 10.1038/s41467-021-26244-5. PMID: 34697316; PMCID: PMC8546149.

Isiaku AI, Zhang Z, Pazhakh V, Manley HR, Thompson ER, Fox LC, Yerneni S, Blombery P, Lieschke GJ.

Transient, flexible gene editing in zebrafish neutrophils and macrophages for determination of cell-autonomous functions.

Dis Model Mech. 2021 Jul 1;14(7):dmm047431. doi: 10.1242/dmm.047431. Epub 2021 Jul 23. PMID: 34296745; PMCID: PMC8319549.

Ratnayake D, Nguyen PD, Rossello FJ, Wimmer VC, Tan JL, Galvis LA, Julier Z, Wood AJ, Boudier T, Isiaku AI, Berger S, Oorschot V, Sonntag C, Rogers KL, Marcelle C, Lieschke GJ, Martino MM, Bakkers J, Currie PD.

Macrophages provide a transient muscle stem cell niche via NAMPT secretion.

Nature. 2021 Mar;591(7849):281-287. doi: 10.1038/s41586-021-03199-7. Epub 2021 Feb 10. PMID: 33568815.

Manley HR, Potter DL, Heddleston JM, Chew TL, Keightley MC, Lieschke GJ.

Frontline Science: Dynamic cellular and subcellular features of migrating leukocytes revealed by in vivo lattice lightsheet microscopy.

J Leukoc Biol. 2020 Aug;108(2):455-468. doi: 10.1002/JLB.3HI0120-589R. Epub 2020 Apr 23. PMID: 32323898.

Isles HM, Loynes CA, Alasmari S, Kon FC, Henry KM, Kadochnikova A, Hales J, Muir CF, Keightley MC, Kadirkamanathan V, Hamilton N, Lieschke GJ, Renshaw SA, Elks PH.

Pioneer neutrophils release chromatin within in vivo swarms.

Elife. 2021 Jul 21;10:e68755.

More Publications

Authors Title Published In

Jiang JH, Bhuiyan MS, Shen HH, Cameron DR, Rupasinghe TWT, Wu CM, Le Brun AP, Kostoulias X, Domene C, Fulcher AJ, McConville MJ, Howden BP, Lieschke GJ, Peleg AY.

Antibiotic resistance and host immune evasion in Staphylococcus aureus mediated by a metabolic adaptation.

Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3722-3727. doi: 10.1073/pnas.1812066116. Epub 2019 Feb 11.

Manley HR, Keightley MC, Lieschke GJ.

The Neutrophil Nucleus: An Important Influence on Neutrophil Migration and Function.

Front Immunol. 2018 Dec 4;9:2867. doi: 10.3389/fimmu.2018.02867. PMID: 30564248; PMCID: PMC6288403.

Ellett F, Pazhakh V, Pase L, Benard EL, Weerasinghe H, Azabdaftari D, Alasmari S, Andrianopoulos A, Lieschke GJ.

Macrophages protect Talaromyces marneffei conidia from myeloperoxidase-dependent neutrophil fungicidal activity during infection establishment in vivo.

PLoS Pathog. 2018 Jun 8;14(6):e1007063. doi: 10.1371/journal.ppat.1007063. eCollection 2018 Jun.

Pazhakh V, Ellett F, Croker BA, O’Donnell JA, Pase L, Schulze KE, Greulich RS, Gupta A, Reyes-Aldasoro CC, Andrianopoulos A, Lieschke GJ.

β-glucan-dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment.

PLoS Biol. 2019 Sep 4;17(9):e3000113. doi: 10.1371/journal.pbio.3000113. eCollection 2019 Sep.

Schmitz U, Pinello N, Jia F, Alasmari S, Ritchie W, Keightley MC, Shini S, Lieschke GJ, Wong JJ, Rasko JEJ.

Intron retention enhances gene regulatory complexity in vertebrates.

Genome Biol. 2017 Nov 16;18(1):216. doi: 10.1186/s13059-017-1339-3.

Witzel M, Petersheim D, Fan Y, Bahrami E, Racek T, Rohlfs M, Puchalka J, Mertes C, Gagneur J, Ziegenheim C, Enard W, Stray-Pederson A, Arkwright P, Abboud M, Pazhakh V, Lieschke GJ, Mundlos S, Krawitz, Dahlhoff M, Schneider M, Wolf E, Horny H-P, Schmidt H, Schaffer A, Klein C.

Chromatin remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.

Nat Genet. 2017 May;49(5):742-752. doi: 10.1038/ng.3833. Epub 2017 Apr 3.

Keightley MC, Carradice DP, Layton JE, Pase L, Bertrand JY, Wittig JG, Dakic A, Badrock AP, Cole NJ, Traver D, Nutt SL, McCoey J, Buckle AM, Heath JK, Lieschke GJ

The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger.

Nat Commun. 2017 Apr 6;8:14911. doi: 10.1038/ncomms14911.

Pazhakh V, Clark S, Keightley MC, Lieschke GJ.

A GCSFR/CSF3R zebrafish mutant models the persistent basal neutrophil deficiency of severe congenital neutropenia.

Sci Rep. 2017 Mar 10;7:44455. doi: 10.1038/srep44455.

Bhuiyan MS, Ellett F, Murray GL, Kostoulias X, Cerqueira GM, Schulze KE, Mahamad Maifiah MH, Li J, Creek DJ, Lieschke GJ, Peleg AY.

Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9599-604. doi: 10.1073/pnas.1523116113. Epub 2016 Aug 9.

Keightley MC, Markmiller S, Love CG, Rasko JE, Lieschke GJ, Heath JK.

Experimental approaches to studying the nature and impact of splicing variation in zebrafish.

Methods Cell Biol. 2016;135:259-88. doi: 10.1016/bs.mcb.2016.02.006. Epub 2016 Mar 9.

Nguyen PD, Hollway GE, Sonntag C, Miles LB, Hall TE, Berger S, Fernandez KJ, Gurevich DB, Cole NJ, Alaei S, Ramialison M, Sutherland RL, Polo JM, Lieschke GJ, Currie PD.

Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1.

Nature. 2014 Aug 21;512(7514):314-8. doi: 10.1038/nature13678. Epub 2014 Aug 13.

Markmiller S, Cloonan N, Lardelli RM, Doggett K, Keightley MC, Boglev Y, Trotter AJ, Ng AY, Wilkins SJ, Verkade H, Ober EA, Field HA, Grimmond SA, Lieschke GJ, Stainier DYR, Heath JK.

Minor class splicing shapes the zebrafish transcriptome during development.

PNAS February 25, 2014 111 (8) 3062-3067. doi: 10.1073/pnas.1305536111. Epub 2014 Feb 10, 2014.

Palha N, Guivel-Benhassine F, Briolat V, Lutfalla G, Sourisseau M, Ellett F, Wang C.-H, Lieschke GJ, Herbomel P, Schwartz O, Levraud J-P.

Real-time visualization of Chikungunya virus infection and host interferon response in zebrafish.

PLoS Pathog. 2013;9(9):e1003619. doi: 10.1371/journal.ppat.1003619. Epub 2013 Sep 5.

Hall CJ, Boyle RH, Astin JW, Flores MV, Oehlers SH, Sanderson LE, Ellett F, Lieschke GJ, Crosier KE, Crosier PS.

Immunoresponsive gene 1 augments bactericidal activity of macrophage-lineage cells by regulating -oxidation-dependent mitochondrial ROS production.

Cell Metab. 2013 Aug 6;18(2):265-78. doi: 10.1016/j.cmet.2013.06.018.

Keightley MC, Crowhurst MO, Layton JE, Beilharz T, Markmiller S, Varma S, Hogan BM, de Jong-Curtain TA, Heath JK, Lieschke GJ.

In vivo mutation of pre-mRNA processing factor 8 (Prpf8) affects transcript splicing, cell survival and myeloid differentiation.

FEBS Lett. 2013 Jul 11;587(14):2150-7. doi: 10.1016/j.febslet.2013.05.030. Epub 2013 May 25.

Lieschke GJ, Oates AC, Kawakami K (eds).

Zebrafish: Methods and Protocols.

Humana Press, Totowa NJ USA, 2009.

Pase L, Layton JE, Kloosterman WP, Carradice D, Waterhouse PM, Lieschke GJ.

miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2.

Blood. 2009 Feb 19;113(8):1794-804. doi: 10.1182/blood-2008-05-155812. Epub 2008 Oct 10.

Lieschke GJ, Currie PD.

Animal models of human disease – zebrafish swim into view.

Nat Rev Genet. 2007 May;8(5):353-67. doi: 10.1038/nrg2091.

Keightley MC, Wang C-H, Pazhakh V, Lieschke GJ.

Delineating the roles of neutrophils and macrophages in zebrafish regeneration models.

Int J Biochem Cell Biol. 2014 Nov;56:92-106. doi: 10.1016/j.biocel.2014.07.010. Epub 2014 Jul 21.

Ellett F, Pase L, Hayman JW, Andrianopoulos A, Lieschke GJ.

mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish.

Blood. 2011 Jan 27;117(4):e49-56. doi: 10.1182/blood-2010-10-314120. Epub 2010 Nov 17. PMID: 21084707; PMCID: PMC3056479.