Sabine Totemeyer

Contact

• workRoom C19 Veterinary Academic Building
  Sutton Bonington Campus
  Sutton Bonington
  Leicestershire
  LE12 5RD
  UK
• work0115 951 6454
• fax0115 951 6440
• sabine.totemeyer@nottingham.ac.uk

Biography

Sabine Tötemeyer obtained a Diplom in Biology (roughly equivalent to MSc) in Microbiology, Biochemistry and Plant Physiology from the University of Osnabrück in Germany. She obtained a PhD from the University of Aberdeen in 1997. She then spent two years as a postdoctoral research associate at the Christian de Duve Institute for Medical Sciences, Université Catholique de Louvain, Brussels, Belgium. This was followed by six years of research in the Cell Biology of Infection Group at the Centre for Veterinary Science, Cambridge Veterinary School, University of Cambridge. She joined the newly formed School of Veterinary Medicien and Science in 2006. She is invovled in module convenign of the Lymphoreticular Cell Biology (LCB) module in Year 1 & 4 and areas of teachign include cell biology, microbiology, host pathogen interactions, innate immunity, antibody based and molecular disgnostics ass well as Personal and Professional Skills (PPS) and communicaitons skills. her research interst include the Role of Toll-like receptors (TLRs) in host-bacteria interactionsand the development of complex epithelial tissue culture models. She also has an iterest in educational research with an emphasis on (1) assessment and feedback, 1st year experience ( and student selection/admission.

Expertise Summary

Sabine Tötemeyer is a Lecturer in Cellular Microbiology, a co-convener for the year 1 module D11LCB and convener for the year 4 module D14LCB. She is also involved in the oragnisation of departmental Research Seminars.

Teaching Summary

I am involved in convening the Lymphoreticular Cell Biology (LCB) modules in year 1 and 4 (D11LCB & D14LCB) covering cell biology, immunology and heammatology. I contribute to other modules… read more

Research Summary

My main interest is in the host-bacterial interactions and the development of complex in vitro tissue culture systems

• Role of Toll-like receptors (TLRs) in host-bacteria interactions

The innate immune system is of crucial importance for achieving homeostasis in the intestinal environment and the host response to pathogens. Toll-like receptors (TLRs) are a family of membrane receptors that recognize a wide range of pathogen associated molecular patterns (PAMPs). We are studying the modulation of TLR expression and cytokine production due to interactions with probiotics and/or pathogens. 1. Interactions of epithelial intestinal cells with commensals and pathogens (incl Clostridium difficile, Salmonella, Vibrio etc) 2. Interaction of bovine caruncular epithelia cells with abortifacient pathogens Leptospira and Listeria, 3. Effect of probiotics on weaning stress in pigs 4. Host pathogen interactions in multi-bacterial infections such as footrot in sheep

• Development of complex epithelial tissue culture models

In research, due to increasing ethical awareness and technical developments, there is an increased need for models that mimic organs and tissues. To achieve better likeness to in vivo situation for the study of disease processes and host we are using and developing complex tissue culture systems 1. bacterial interactions in the intestinal tract, we are developing 3D tissue culture using rotary systems and reduced oxygen concentration. 2. Air interface culture systems 3. Organoid models using feeder cells to sustain tissue biopsies/necropsies

• Educational Research

My areas of interest include 1. Assessment and feedback 2. First year experience (graduate students, international students) 3. Student selection/admission

Recent Publications

• SHERWOOD V, KING E, TÖTEMEYER S, CONNERTON I and MELLITS KH, 2012. Interferon Treatment Suppresses Enteric Adenovirus Infection In A Model Gastrointestinal Cell Culture System. The Journal Of General Virology. 93(3), 618-623
• TARLINTON, RE, YON, L, KLISCH, K, TOTEMEYER, S and GOUGH, KC, 2011. Confidence As A Barrier To The Use Of Problem-Based Learning In Veterinary Undergraduate Students Journal Of Veterinary Medical Education. 38(3), 305-310
• LE BON, M, DAVIES, HE, GLYNN, C, THOMPSON, C, MADDEN, M, WISEMAN, J, DODD, CER, HURDIDGE, L, PAYNE, G, LE TREUT, Y and CRAIGON, J, TÖTEMEYER, S. AND MELLITS, KH, 2010. Influence of probiotics on gut health in the weaned pig Lifestock Science. 133, 179-181
• WRIGHT, J.A.*, TÖTEMEYER, S.*, HAUTEFORT, I, APPIA-AYME, C, ALSTON, M, DANINO, V, PATERSON, G.K, MASTROENI, P, MÉNAGER, N, ROLFE, M, THOMPSON, A, UGRINOVIC, S, SAIT, L, HUMPREY, T, NORTHEN, H, PETERS, S.E, MASKELL, D.J and HINTON, J.C. AND BRYANT,C.E, 2009. Multiple redundant stress resistance mechanisms are induced in Salmonella enterica serovar Typhimurium in response to alteration of the intracellular environment via TLR4 signalling. Microbiology. 155, 472-83

• View all publications

I am involved in convening the Lymphoreticular Cell Biology (LCB) modules in year 1 and 4 (D11LCB & D14LCB) covering cell biology, immunology and heammatology. I contribute to other modules teaching various aspets of cell biology, host pathogen interactions, antibody based diagnostic tests and molecular biology. I am also involved in teaching PPS and communication skills in years 1-3.

Past Research

(1) Role of Toll like receptors in Salmonella infection

My work involves the analysis of bacterial growth and the host immune response mediated by toll like receptors (TLRs) during Salmonella infection in vivo (mouse typhoid model) and in vitro (bone marrow derived macrophages (BMDM) & cell lines). I have investigated the mRNA expression of TLR2, TLR4, and MD2 in spleens and livers of C3H/HeN mice (carrying wild-type TLR4) and C3H/HeJ mice (carrying mutated TLR4) in response to Salmonella infection. During Salmonella infections, TLR4 is activated, leading to increased TLR2 and decreased TLR4 expression (Tötemeyer et al., 2003). I also characterized the expression of a wide range of TLRs, TLR associated molecules and inflammatory mediators in C57/BL6 mice (Tötemeyer et al., 2005). In BMDM in response to Salmonella infection, production of nitric oxide (NO) is fully dependent on the activation of TLR4, while the production of TNFS is only partially TLR4 dependent (Royle et al., 2003). TLR4 plays an important role in SipB independent Salmonella induced cell death via the adapter molecules Trif and Tram (Cook, Tötemeyer et al. 2007). Stimulation of bone marrow derived macrophages with IFNg results in the production of NO in response to the bacterial cell wall component peptidoglycan in a TLR independent, Nod dependent way (Tötemeyer et al 2006).

(2) Adaptation of bacteria to intracellular environment

Array technology was used to investigating how Salmonella adapts to the intracellular macrophage environment. Infection of BMDMs from phox^-/- and TLR4^-/- mice followed by isolation of bacterial RNA allowed to determine the changes occurring in Salmonella gene expression using microarrays. I identified known genes required for the adaptation to an environment containing reactive oxygen species as well as genes of unknown function that might also be critical for S. typhimurium survival within macrophages (Wright, Tötemeyer et al, in preparation).

• SHERWOOD V, KING E, TÖTEMEYER S, CONNERTON I and MELLITS KH, 2012. Interferon Treatment Suppresses Enteric Adenovirus Infection In A Model Gastrointestinal Cell Culture System. The Journal Of General Virology. 93(3), 618-623
• TARLINTON, RE, YON, L, KLISCH, K, TOTEMEYER, S and GOUGH, KC, 2011. Confidence As A Barrier To The Use Of Problem-Based Learning In Veterinary Undergraduate Students Journal Of Veterinary Medical Education. 38(3), 305-310
• LE BON, M, DAVIES, HE, GLYNN, C, THOMPSON, C, MADDEN, M, WISEMAN, J, DODD, CER, HURDIDGE, L, PAYNE, G, LE TREUT, Y and CRAIGON, J, TÖTEMEYER, S. AND MELLITS, KH, 2010. Influence of probiotics on gut health in the weaned pig Lifestock Science. 133, 179-181
• WRIGHT, J.A.*, TÖTEMEYER, S.*, HAUTEFORT, I, APPIA-AYME, C, ALSTON, M, DANINO, V, PATERSON, G.K, MASTROENI, P, MÉNAGER, N, ROLFE, M, THOMPSON, A, UGRINOVIC, S, SAIT, L, HUMPREY, T, NORTHEN, H, PETERS, S.E, MASKELL, D.J and HINTON, J.C. AND BRYANT,C.E, 2009. Multiple redundant stress resistance mechanisms are induced in Salmonella enterica serovar Typhimurium in response to alteration of the intracellular environment via TLR4 signalling. Microbiology. 155, 472-83
• TALBOT, SUZANNE, TÖTEMEYER, SABINE, YAMAMOTO, MASAHIRO, AKIRA, SHIZUO, HUGHES, KATHERINE, GRAY, DAVID, BARR, TOM, MASTROENI, PIETRO, MASKELL, DUNCAN J and BRYANT, CLARE E, 2009. Toll-like receptor 4 signalling through MyD88 is essential to control Salmonella enterica serovar typhimurium infection, but not for the initiation of bacterial clearance. Immunology. 128(4), 472-83
• SMYTH, TOMOKO, TÖTEMEYER, SABINE, HAUGLAND, SEAN, WILLERS, CHRISSIE, PETERS, SARAH, MASKELL, DUNCAN and BRYANT, CLARE, 2008. Dexamethasone modulates Salmonella enterica serovar Typhimurium infection in vivo independently of the glucocorticoid-inducible protein annexin-A1. FEMS Immunology and Medical Microbiology. 54(3), 339-48
• COOK,, TÖTEMEYER,, STEVENSON,, FITZGERALD,, YAMAMOTO,, AKIRA,, MASKELL, and BRYANT,, 2007. Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif. Immunology. 122(2), 222-9
• TÖTEMEYER, S., SHEPPARD, M., LLOYD, A., ROPER, D., DOWSON, C., UNDERHILL, D., MURRAY, P., MASKELL, D. and BRYANT, C., 2006. IFN-γ enhances production of nitric oxide from macrophages via a mechanism that depends on nucleotide oligomerization domain-2 Journal of Immunology. 176(8), 4804-4810
• SMYTH, TOMOKO, HARRIS, HAYLEY J, BROWN, ANDREW, TÖTEMEYER, SABINE, FARNFIELD, BELINDA A, MASKELL, DUNCAN J, MATSUMOTO, MAKOTO, PLEVIN, ROBIN, ALLDRIDGE, LOUISE C and BRYANT, CLARE E, 2006. Differential modulatory effects of annexin 1 on nitric oxide synthase induction by lipopolysaccharide in macrophages. Immunology. 117(3), 340-9
• TÖTEMEYER, S., KAISER, P., MASKELL, D.J. and BRYANT, C.E., 2005. Sublethal infection of C57BL/6 mice with <i>Salmonella enterica</i> serovar Typhimurium leads to an increase in levels of Toll-like receptor 1 (TLR1), TLR2, and TLR9 mRNA as well as a decrease in levels of TLR6 mRNA in infected organs. Infection and immunity. 73(3), 1873-1878
• JONES, M.A., TÖTEMEYER, S., MASKELL, D.J., BRYANT, C.E. and BARROW, P.A., 2003. Induction of proinflammatory responses in the human monocytic cell line THP-1 by<i> Campylobacter jejuni</i> Infection and Immunity. 71(5), 2626-2633
• TOTEMEYER, S., FOSTER, N., KAISER, P., MASKELL, D. J. and BRYANT, C. E., 2003. Toll-Like Receptor Expression in C3H/HeN and C3H/HeJ Mice during <i>Salmonella enterica</i> Serovar Typhimurium Infection Infection and Immunity. VOL 71(PART 11), 6653-6657
• ROYLE, M.C J., TÖTEMEYER, S., ALLDRIDGE, L.C, MASKELL, D.J and BRYANT, C.E., 2003. Stimulation of Toll-like receptor 4 by lipopolysaccharide during cellular invasion by live <i>Salmonella typhimurium</i> is a critical but not exclusive event leading to macrophage responses. Journal of Immunology (Baltimore, Md. : 1950). 170(11), 5445-54
• DENECKER, GEERTRUI, TÖTEMEYER, SABINE, MOTA, LUÍS J, TROISFONTAINES, PAUL, LAMBERMONT, ISABELLE, YOUTA, CARINE, STAINIER, ISABELLE, ACKERMANN, MARTIN and CORNELIS, GUY R, 2002. Effect of low- and high-virulence Yersinia enterocolitica strains on the inflammatory response of human umbilical vein endothelial cells. Infection and immunity. 70(7), 3510-20
• TOTEMEYER, S. and CORNELIS, G. R., 2002. Transport and Intracellular Movement-Protein Translocation via Dedicated Secretion Systems METHODS IN MICROBIOLOGY. ISSU 31, 263-276
• STAINIER, I, BLEVES, S, JOSENHANS, C, KARMANI, L, KERBOURCH, C, LAMBERMONT, I, TÖTEMEYER, S, BOYD, A and CORNELIS, G R, 2000. YscP, a Yersinia protein required for Yop secretion that is surface exposed, and released in low Ca2+. Molecular microbiology. 37(5), 1005-18
• BOYD, A P, GROSDENT, N, TÖTEMEYER, S, GEUIJEN, C, BLEVES, S, IRIARTE, M, LAMBERMONT, I, OCTAVE, J N and CORNELIS, G R, 2000. Yersinia enterocolitica can deliver Yop proteins into a wide range of cell types: development of a delivery system for heterologous proteins. European journal of cell biology. 79(10), 659-71
• LEVINA, N, TÖTEMEYER, S, STOKES, N R, LOUIS, P, JONES, M A and BOOTH, I R, 1999. Protection of Escherichia coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity. The EMBO journal. 18(7), 1730-7
• FERGUSON, G P, TÖTEMEYER, S, MACLEAN, M J and BOOTH, I R, 1998. Methylglyoxal production in bacteria: suicide or survival? Archives of microbiology. 170(4), 209-18
• TÖTEMEYER, S, BOOTH, N A, NICHOLS, W W, DUNBAR, B and BOOTH, I R, 1998. From famine to feast: the role of methylglyoxal production in Escherichia coli. Molecular microbiology. 27(3), 553-62