Martin Turner (scientist)

Martin Turner
NationalityBritish
Alma mater
Scientific career
Fieldsimmunology, molecular biology
Institutions
Thesis Regulation of cytokine gene expression  (1990)
Websitewww.babraham.ac.uk/our-research/lymphocyte/martin-turner

Martin Turner is a molecular biologist and Immunologist and Head of the Immunology Programme at the Babraham Institute. His work has helped identify key molecular processes involved in the development of the immune system and its response to pathogens. His work has included research the fundamental mechanisms regulating gene expression by cells of the immune system.

Career

Turner graduated in Biochemistry from University College London and went on to complete a PhD with Professor Sir Marc Feldmann studying the regulation of cytokine gene expression. Subsequently, he joined the MRC National Institute for Medical Research, working with Victor Tybulewicz before joining the Babraham Institute in 1997. Turner became Head of the Lymphocyte Signalling & Development Programme at the Institute in 2005. In 2021 this became the Immunology Programme.

Research

During his PhD, Turner contributed to fundamental research that led to the identification of TNF as a potential drug target for the treatment of rheumatoid arthritis.[1][2][3][4][5]

He went on to work on identifying elements of signal transduction pathways that are needed inside cells to promote proper development of lymphocytes.[6][7][8][9] His work has continued to focus in this area and has included identifying roles for phosphoinositide-3-kinase (PI3K) in lymphocyte development and activation.[10][11][12][13][14][15][16][17][18] This work has helped to underpin the development of PI3K delta inhibitors in treating human cancers.

Recent work by his group seeks to understand how RNA-processing mechanisms control the development and function of B and T lymphocytes.[19][20][21] In particular, Turner is interested in RNA-binding proteins[22][23][24][25][26][27][28][29][30][31][32] and microRNAs (particularly miR-155[33][34][35][36][37] and how these function within signal transduction networks to control cell differentiation and immunity.

References

  1. ^ Gray, P.W., Barrett, K., Chantry, D., Turner, M., and Feldmann, M. (1990). “Cloning of human tumour necrosis factor receptor cDNA and expression of recombinant soluble TNF binding protein.” Proc. Natl. Acad. Sci. USA 87:7380-7384.
  2. ^ Turner, M., Chantry, D., Buchan, G., Barrett, K., and Feldmann, M. (1989). “Regulation of expression of human interleukin 1 alpha and beta genes.” J. Immunol. 143:3556-3561.
  3. ^ Hirano, T., Matsuda, T., Turner, M., Noboyuki, M., Buchan, G., Tang, B., Sato, K., Shimzu, M., Maini, R.N., Feldmann, M., and Kishimoto, T. (1988). “Excessive production of interleukin 6 (BSF-2) in rheumatoid arthritis.” Eur. J. Immunol. 18:1797-1801.
  4. ^ Buchan, G., Barrett, K., Turner, M., Chantry, D., Maini, R. N., and Feldmann, M. (1988). “Interleukin 1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1alpha.” Clin. Exp. Immunol. 73:443-449.
  5. ^ Turner, M., Londei, M., and Feldmann, M. (1987). “Human T cells from normal and autoimmune individuals can produce Tumour Necrosis Factor.” Eur. J. Immunol. 17:1807-1814.
  6. ^ Turner, M., Gulbranson-Judge, A., Quinn, M., Walters, A. E., MacLennan, I. C. M. and Tybulewicz, V. L. J. (1997). “Syk tyrosine kinase is required for the positive selection of immature B cells into the recirculating pool”. J. Exp. Med. 186: 2013-2021.
  7. ^ Turner, M., Mee, P. J., Walters A. E., Quinn, M. E., Mellor, A. L., Zamoyska, R. and Tybulewicz, V. L. J. (1997). “A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of T lymphocytes”. Immunity. 7: 451-460.
  8. ^ Turner, M., Mee, P. J., Costello, P. S., Williams, O., Price, A. A., Duddy, L. P., Furlong, M. T., Geahlen, R. L. and Tybulewicz, V. L. J. “Perinatal lethality and blocked B cell development in mice lacking the tyrosine kinase Syk”. (1995). Nature. 378: 298-302.
  9. ^ Tarakhovsky, A$., Turner,M$., Schall, S., Mee, P.J., Duddy, L. P., Rajewsky, K., and Tybulewicz, V. L. J. (1995). “Defective antigen receptor mediated proliferation of B and T cells in the absence of Vav.” Nature. 374: 467-470. $ joint first authorship.
  10. ^ Janas M.L., and Turner M. (2011) PreTCR dependent proliferation requires CXCR4 activation of p110gamma by a Ras dependent mechanism. J. Immunol. 187:4667-75. PMID 21930962
  11. ^ Rolf J, Bell S.E., Kovesdi D., Janas M.L., Soond D.R., Webb L.M., Santinelli S., Saunders T., Hebeis B., Killeen N., Okkenhaug K, and Turner M. (2010). Phosphoinositide 3-Kinase Activity in T Cells Regulates the Magnitude of the Germinal Center Reaction. J. Immunol. 185: 4042-4052 PMID 20826752. Selected as a highlight paper
  12. ^ Janas, M. L., Varano, G., Gudmundsson, K., Noda, M., Nagasawa, T., Turner, M. (2010) Thymic development beyond β-selection requires phosphatidylinositol 3-kinase activation by CXCR4. J. Exp. Med. 207:247-61. PMID 20038597
  13. ^ Janas, M. L., Hodson, D., Stamataki, Z., Hill, S., Welch, K., Gambardella, L., Trotman, L., Pandolfi, P-P., Vigorito, E., and Turner, M (2008). The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells. J. Immunol. 180:739-46. PMID 18178811
  14. ^ Llorian M., Stamataki, Z., Hill, S., Turner, M. and Martensson I-L. (2007) “Cutting Edge: P110delta is required for down-regulation of RAG expression in immature B cells.” J. Immunol. 178:1981-1985.
  15. ^ McKenzie G, Ward G, Stallwood Y, Briend E, Papadia S, Lennard A, Turner M, Champion B and Hardingham GE. (2006). “Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals”. BMC Cell Biol. 7:10.
  16. ^ Webb, L., Vigorito, E., Wymann, M.P,. Hirsch, E and Turner M. (2005) “Cutting Edge: T Cell Development Requires the Combined Activities of the p110gamma and p110delta Catayltic Isoforms of PI3K”. J Immunol. 175: 2783-2787.
  17. ^ Vigorito, E., Bardi, G., Glassford, J., Lam Eric E. W.-F., Clayton, E., and Turner, M. (2004). “Vav-dependent and Vav-independent PI3K activation in murine B cells determined by the nature of the stimulus”. J. Immunol. 173:3209-3214.
  18. ^ Clayton, E., Bardi, G., Bell, S. E., Chantry, D., Downes, C. P., Gray, A., Humphries, L. A., Rawlings, D., Reynolds, H., Vigorito, E. and Turner, M. (2002). A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J. Exp. Med. 196 753-763.
  19. ^ Turner M, and Díaz-Muñoz MD. (2018) “RNA-binding proteins control gene expression and cell fate in the immune system.” Nature Immunology 19(2):120-129. Review. PMID 29348497
  20. ^ Galloway A, and Turner M. (2017) Cell cycle RNA regulons coordinating early lymphocyte development. Wiley Interdiscip. Rev. RNA. Feb 23. doi: 10.1002/wrna.1419. Review. PMID 28231639.
  21. ^ Turner M, Galloway A and Vigorito E (2014) “Non-coding RNA and its Associated Proteins as Regulatory Elements of the immune system” Nature Immunology 15:484-91. Review. PMID 24840979.
  22. ^ Monzón-Casanova E., Screen M., Coulson, R.M.R., Diaz-Munoz M.D., Bell S.E., Lamers G., Solimena M., Smith C. and Turner M. (2018) “The RNA binding protein PTBP1 is necessary for B cell selection in germinal centres.” Nature Immunology 19 (3) March 267-278. PMID 29358707
  23. ^ Rebecca Newman, Helena Ahlfors, Alexander Saveliev, Alison Galloway, Charlotte Cook, Daniel J Hodson, Robert Williams, Adam Cunningham, Sarah E Bell and Martin Turner. “Maintenance of the marginal zone B cell compartment specifically requires the RNA binding protein ZFP36l1” Nature Immunology June 2017. 18(6):683-693. PMID 28394372
  24. ^ Galloway, A., Saveliev, A., Łukasiak, S., Hodson, D.J., Bolland, D., Balmanno, K., Ahlfors, H., Monzón-Casanova, E., Ciullini-Mannurita, S., Bell, L.S., Andrews, S. R., Díaz-Muñoz, M.D., Cook, S. J., Corcoran, A. and Turner M. “RNA binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence". Science 352:453 PMID 27102483
  25. ^ Vogel, K. U., Bell, L. S., Galloway, A., Ahlfors, H., and Turner, M. (2016) "The RNA-binding proteins Zfp36l1 and Zfp36l2 enforce the thymic β-selection checkpoint by limiting DNA damage response signaling and cell cycle progression" J. Immunol. 197(7):2673-85. PMID 27566829
  26. ^ Diaz-Muñoz,. M. D., Bell, S.E., Fairfax, K., Monzon-Casanova, E., Cunningham, A.F. Gonzalez-Porta, M., Andrews, S.R., Bunik, V. I., Zarnack, K., Curk, T., Ward A. Heggermont, W.A., Heymans, S., Gibson, G.E., Kontoyiannis, D. L., Ule, J., and Turner M. (2015) HuR-dependent regulation of mRNA splicing is essential for the B cell antibody response. Nature Immunology (4):415-25. PMID 25706746
  27. ^ Hodson, D. J., Janas, M. L., Galloway, A. Bell, S.E., Andrews, S., Li, C.M., Pannell, R. Siebel, C.W., MacDonald, H. R., De Keersmaecker, K., Ferrando, A.A., Grutz, G., and Turner, M. (2010). Deletion of the RNA-binding proteins zfp36L1 and zfp36L2 leads to perturbed thymic development and T-lymphoblastic leukaemia. Nat. Immunol. 11(8):717-724. PMID 20622884.
  28. ^ Turner, D. J., Saveliev, A., Salerno, F., Matheson, L. S., Screen, M., Lawson, H., Wotherspoon, D., Kranc, K. R., and Turner, M. (2022). A functional screen of RNA binding proteins identifies genes that promote or limit the accumulation of CD138+ plasma cells. PMID 35451955.
  29. ^ D'Angeli, V., Monzón-Casanova, E., Matheson, L. S., Gizlenci, Ö., Petkau, G., Gooding, C., Berrens, R. V., Smith, C., and Turner, M. (2022). Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells. European Journal of Immunology.PMID 35460072.
  30. ^ Matheson, L. S., Petkau, G., Sáenz-Narciso, B., D'Angeli, V., McHugh, J., Newman, R., Munford, H., West, J., Chakraborty, K., Roberts, J., Łukasiak, S., Díaz-Muñoz, M. D., Bell, S. E., Dimeloe, S., and Turner, M. (2022). Multiomics analysis couples mRNA turnover and translational control of glutamine metabolism to the differentiation of the activated CD4+ T cell. Scientific reports, 12(1), 19657. PMID 36385275. PMID 35460072.
  31. ^ Petkau, G., Mitchell, T. J., Chakraborty, K., Bell, S. E., D’Angeli, V., Matheson, L., Turner, D. J., Saveliev, A., Gizlenci, O., Salerno, F., Katsikis, P. D., and Turner, M. (2022). The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins. Nature Communications, 13(1), 2274. PMID 35477960.
  32. ^ Salerno, F., Howden, A. J. M., Matheson, L. S., Gizlenci, Ö., Screen, M., Lingel, H., Brunner-Weinzierl, M. C., & Turner, M. (2023). An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells. Nature communications, 14(1), 5116. PMID 37612319.
  33. ^ Lu D., Nakagawa R., Lazzaro S., Staudacher P., Abreu-Goodger C., Henley T., Boiani S., Leyland R., Galloway A., Andrews S., Butcher G., Nutt S.L, Turner M*., Vigorito E*.. (2014) The miR-155/PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation. J. Exp. Med. 211:2183-98. PMID 25288398 (*co-corresponding authors).
  34. ^ Gracias DT, Stelekati E, Hope JL, Boesteanu AC, Fraietta JA, Doering T, Norton J, Mueller YM, Wherry EJ, Turner M*, Katsikis PD (2013) MicroRNA-155 controls CD8+ T cell responses by regulating interferon signaling. Nature Immunology 14:593-602. PMID 23603793 (*co-corresponding author).
  35. ^ Kohlhaas, S., Garden, O.A,, Scudamore, C., Turner, M., Okkenhaug, K., Vigorito, E. (2009). Cutting edge: The Foxp3 target miR-155 contributes to the development of regulatory T cells. J. Immunol. 182:2578-2582. PMID 19234151
  36. ^ Vigorito E, Kerry L Perks, Cei Abreu-Goodger, Sam Bunting, Zou Xiang, Susan Kohlhaas, Partha P. Das, Eric A. Miska, Antony Rodriguez, Allan Bradley, Kenneth G. C. Smith, Cristina Rada, Anton J. Enright, Kai-Michael Toellner, Ian C. MacLennan and Turner, M. (2007). MicroRNA-155 regulates the generation of Immunoglobulin class-switched plasma cells. Immunity 27:847-59.
  37. ^ Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M*, Bradley A*. (2007). Requirement of bic/microRNA-155 for normal immune function. Science. 316:608-11. * Corresponding Authors