The Ramaciotti Immunization Genomics Laboratory was established in 2008 through a Major Initiative Award from the Clive and Vera Ramaciotti Foundation to Associate Professor Anselm Enders and Professor Chris Goodnow. By analysing mice after random ENU mutagenesis we aim to elucidate new genes and mechanisms controlling the development and function of the immune system.
Since then, the main focus of the lab has been the investigation of novel pathways regulating B cell development and function. This work has lead to the discovery of many strains of mice with a defect in either the development or function of B cells and other lymphocytes subsets. Detailed analysis of these mice has led to the discovery of functions for previously uncharacterized genes or to the description of specific and previously unknown functions to otherwise well-studied genes.
Key outcomes from this approach were the discovery that flipping of phospholipids across the cell membrane is essential for normal development of B cells in the bone marrow (Yabas et al, Nature Immunology 12:441-449, 2011) and an essential role for the intramembrane endopeptidase SPPL2A for survival and function of mature B cells and CD8- dendritic cells (Bergmann et al, The Journal of experimental medicine 210:31-40, 2013).
As part of the Centre for Personalized Immunology (CPI), an NHMRC funded Center for Research Excellence, my group is investigating the pathogenesis of novel primary immunodeficiencies. In cooperation with clinicians and researchers from Australia and Germany, we are sequencing the genome from patients with unexplained primary immunodeficiencies. This work has led to the discovery of likely causal mutations in genes not previously associated with immune defects. To follow up on these mutations we are now generating matching mouse models and will analyze these to better understand the disease pathogenesis in the patients.
Research support officer
- Yabas, M, Coupland, LA, Cromer, D, Winterberg, M, Teoh, NC, D'Rozario, J, Kirk, K, Bröer, S, Parish, CR and Enders, A., 2014, Mice deficient in the putative phospholipid flippase ATP11C exhibit altered erythrocyte shape, anemia, and reduced erythrocyte life span. Journal of Biological Chemistry 289(28):19531–7.
- Enders, A, Short, A, Miosge, LA, Bergmann, H, Sontani, Y, Bertram, EM, Whittle, B, Balakishnan, B, Yoshida, K, Sjollema, G, Field, MA, Andrews, TD, Hagiwara, H and Goodnow, CC., 2014, Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes. Proc Natl Acad Sci USA 111(12):4513-4518.
- Crawford, G*, Enders, A*, Gileadi, U* (*Equal contribution), Stankovic, S, Zhang, Q, Lambe, T, Crockford, TL, Lockstone, HE, Freeman, A, Arkwright, PD, Smart, JM, Ma, CS, Tangye, SG, Goodnow, CC, Cerundolo, V, Godfrey, DI, Su, HC, Randall, KL and Cornall, RJ., 2013, DOCK8 is critical for the survival and function of NKT cells. Blood 122(12):2052–61. r 10.
- Teh, CE, Horikawa, K, Arnold, CN, Beutler, B, Kucharska, EM, Vinuesa, CG, Bertram, EM, Goodnow, CC and Enders, A., 2013, Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation. Genes and Immunity 14:223-33.
- Stepensky, P, Keller, B, Buchta, M, Kienzler, AK, Elpeleg, O, Somech, R, Cohen, S, Shachar, I, Miosge, LA, Schlesier, M, Fuchs, I, Enders, A, Eibel, H, Grimbacher, B and Warnatz, K., 2013, Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. The Journal of allergy and clinical immunology 131:477-485.
- Bergmann, H, Yabas, M, Short, A, Miosge, L, Barthel, N, Teh, CE, Roots, CM, Bull, KR, Jeelall, Y, Horikawa, K, Whittle, B, Balakishnan, B, Sjollema, G, Bertram, EM, Mackay, F, Rimmer, AJ, Cornall, RJ, Field, MA, Andrews, TD, Goodnow, CC and Enders, A., 2013, B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8- dendritic cells require the intramembrane endopeptidase SPPL2A. The Journal of experimental medicine 210:31-40.
- Enders, A, Stankovic, S, Teh, C, Uldrich, AP, Yabas, M, Juelich, T, Altin, JA, Frankenreiter, S, Bergmann, H, Roots, CM, Kyparissoudis, K, Goodnow, CC and Godfrey, DI., 2012, ZBTB7B (Th-POK) regulates the development of IL-17-producing CD1d-restricted mouse NKT cells. Journal of immunology 189:5240-9.
- Yabas, M, Teh, CE, Frankenreiter, S, Lal, D, Roots, CM, Whittle, B, Andrews, DT, Zhang, Y, Teoh, NC, Sprent, J, Tze, LE, Kucharska, EM, Kofler, J, Farell, GC, Bröer, S, Goodnow, CC and Enders, A., 2011, ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes. Nature Immunology 12:441-449.
- Teh, CE, Daley, SR, Enders, A* and Goodnow, CC* (* Equal contribution)., 2010, T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency. Proceedings of the National Academy of Sciences of the United States of America.