Martin Turner (scientist)

Last updated

Martin Turner
Nationality British
Alma mater
Scientific career
Fields immunology, molecular biology
Institutions
Thesis Regulation of cytokine gene expression  (1990)
Website www.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.

Contents

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.

Related Research Articles

<span class="mw-page-title-main">Immunoglobulin D</span> Antibody isotype

Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM. IgD is also produced in a secreted form that is found in very small amounts in blood serum, representing 0.25% of immunoglobulins in serum. The relative molecular mass and half-life of secreted IgD is 185 kDa and 2.8 days, respectively. Secreted IgD is produced as a monomeric antibody with two heavy chains of the delta (δ) class, and two Ig light chains.

<span class="mw-page-title-main">Perforin-1</span> Mammalian protein found in Homo sapiens

Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxic protein housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Together, these cells are known as cytotoxic lymphocytes (CLs).

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

<span class="mw-page-title-main">Tyrosin-protein kinase Lck</span> Lymphocyte protein

Tyrosin-protein kinase Lck is a 56 kDa protein that is found inside lymphocytes and encoded in the human by the LCK gene. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">P110δ</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform also known as phosphoinositide 3-kinase (PI3K) delta isoform or p110δ is an enzyme that in humans is encoded by the PIK3CD gene.

<span class="mw-page-title-main">CD28</span> Mammalian protein found in humans

CD28 is a protein expressed on T cells that provides essential co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T-cell receptor (TCR), it enhances the production of various interleukins, particularly IL-6. CD28 serves as a receptor for CD80 (B7.1) and CD86 (B7.2), proteins found on antigen-presenting cells (APCs).

<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.

<span class="mw-page-title-main">Interleukin 15</span> Cytokine with structural similarity to Interleukin-2

Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.

<span class="mw-page-title-main">Interleukin 22</span> Protein, encoded in humans by IL22 gene

Interleukin-22 (IL-22) is a protein that in humans is encoded by the IL22 gene.

CD58, or lymphocyte function-associated antigen 3 (LFA-3), is a cell adhesion molecule expressed on Antigen Presenting Cells (APCs), particularly macrophages, and other tissue cells.

<span class="mw-page-title-main">PRKCQ</span> Protein-coding gene in the species Homo sapiens

Protein kinase C theta (PKC-θ) is an enzyme that in humans is encoded by the PRKCQ gene. PKC-θ, a member of serine/threonine kinases, is mainly expressed in hematopoietic cells with high levels in platelets and T lymphocytes, where plays a role in signal transduction. Different subpopulations of T cells vary in their requirements of PKC-θ, therefore PKC-θ is considered as a potential target for inhibitors in the context of immunotherapy.

<span class="mw-page-title-main">SEMA4D</span>

Semaphorin-4D (SEMA4D) also known as Cluster of Differentiation 100 (CD100), is a protein of the semaphorin family that in humans is encoded by the SEMA4D gene.

<span class="mw-page-title-main">LSP1</span> Protein-coding gene in the species Homo sapiens

Lymphocyte-specific protein 1 is a protein that in humans is encoded by the LSP1 gene.

<span class="mw-page-title-main">RFX5</span> Protein-coding gene in the species Homo sapiens

DNA-binding protein RFX5 is a protein that in humans is encoded by the RFX5 gene.

<span class="mw-page-title-main">CD6</span> Human protein

CD6 is a human protein encoded by the CD6 gene.

<span class="mw-page-title-main">ZFP36L1</span> Protein-coding gene in the species Homo sapiens

Butyrate response factor 1 is a protein that in humans is encoded by the ZFP36L1 gene.

<span class="mw-page-title-main">CD8A</span> Protein-coding gene in humans

T-cell surface glycoprotein CD8 alpha chain, is a protein encoded by CD8A gene.

miR-155 Non-coding RNA in the species Homo sapiens

MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases.

<span class="mw-page-title-main">NKG2D</span> Protein-coding gene in the species Homo sapiens

NKG2D is an activating receptor (transmembrane protein) belonging to the NKG2 family of C-type lectin-like receptors. NKG2D is encoded by KLRK1 (killer cell lectin like receptor K1) gene which is located in the NK-gene complex (NKC) situated on chromosome 6 in mice and chromosome 12 in humans. In mice, it is expressed by NK cells, NK1.1+ T cells, γδ T cells, activated CD8+ αβ T cells and activated macrophages. In humans, it is expressed by NK cells, γδ T cells and CD8+ αβ T cells. NKG2D recognizes induced-self proteins from MIC and RAET1/ULBP families which appear on the surface of stressed, malignant transformed, and infected cells.

CD94/NKG2 is a family of C-type lectin receptors which are expressed predominantly on the surface of NK cells and a subset of CD8+ T-lymphocyte. These receptors stimulate or inhibit cytotoxic activity of NK cells, therefore they are divided into activating and inhibitory receptors according to their function. CD94/NKG2 recognize nonclassical MHC glycoproteins class I (HLA-E in human and Qa-1 molecules in the mouse).

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
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