E: Aude.Fahrer@anu.edu.au
T: (+61 2) 6125 4942
F: (+61 2) 6125 0313

BIOL3141: Infection and Immunity (Convenor)
BIOL3144: Molecular Immunology
BIOL1008: Human Biology

Katharine Gosling- PhD student
Angelo Theodoratos- PhD student
Lydia Makaroff- PhD student

Identification of novel genes important in the immune system.
Now that the human and mouse genomes have been sequenced, the next major challenge is to determine the function of each of the genes. One of the most efficient ways of identifying novel genes in the immune response is through phenomics. Random mutations are introduced into the DNA of mice, and the mice are screened for immunological abnormalities. Interesting mice are bred to establish a new strain, carrying the mutation of interest. The mouse strain is studied to identify the mutated gene, and to determine how the mutated gene interferes with the immune response. In this way, novel genes can be identified, and their function determined.

The lab works on two mouse strains with immunological phenotypes; "Nessy" and "Jasmine". Both strains were developed in the Medical Genome Centre, JCSMR, ANU. The Nessy mouse strain has been shown to have defects in thymic T cell development. Thymocyte are partially blocked at the early, CD4-CD8- stage of maturation. Nessy mice have much smaller thymuses than normal mice. Their peripheral T cells show abnormal patterns of cell surface activation markers. These defects are caused by a mutation in a novel gene. Work in the lab is centred on precisely characterising the immunological defects in this mouse strain, and understanding the biochemical pathways affected by the mutated gene.

Katharine M Gosling, Christopher C. Goodnow, Naresh K. Verma, Aude M. Fahrer. Defective T cell function leading to reduced antibody production in a kleisin-b mutant mouse (2008) Immunology

Gosling KM, Makaroff LE, Theodoratos A, Kim YH, Whittle B, Rui L, Wu H, Hong NA, Kennedy GC, Fritz JA, Yates AL, Goodnow CC, & Fahrer AM. A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development. PNAS 2007 104 (30):12445-12450

Liston, A., Lesage, S., Gray, D.H., O'Reilly, L.A., Strasser, A., Fahrer, A.M., Boyd, R.L., Wilson, J., Baxter, A.G., Gallo, E.M., Crabtree, G.R., Peng, K., Wilson, S.R. and Goodnow, C.C. (2004) Generalized resistance to thymic deletion in the NOD mouse; a polygenic trait characterized by defective induction of Bim. Immunity, Dec;21 (6): 817-30.

Fahrer, A.M., Bazan, J.F., Papathanasiou, P., Nelms, K.A. and Goodnow, C.C. (2001)
A genomic view of immunology. Nature 409, 836-838.

Fahrer, A.M., Konigshofer, Y., Kerr, E.M., Ghandour, G., Mack, D.H., Davis, M.M. and Chien, Y.H.(2001) Attributes of gd intraepithelial lymphocytes as suggested by their transcriptional profile PNAS 98, 10261-10266.

Crowley, M.P., Fahrer, A.M., Baumgarth, N., Hampl, J., Gutgemann, I., Teyton, L. and Chien, Y. (2000) A population of murine gamma delta T cells that recognize an inducible MHC class Ib molecule. Science 287, 314-6.

Gütgemann, I., Fahrer, A.M., Altman, J.D., Davis, M.M. and Chien, Y-h. (1998) Induction of rapid T cell activation and tolerance by systemic presentation of an orally administered antigen. Immunity 8, 667-673.

Fahrer, A.M., Geysen, H.M., White, D.O., Jackson, D.C. and Brown, L.E. (1995) Analysis of the requirements for class II-restrictedT-cell recognition of a single determinant reveals considerable diversity in the T-cell response and degeneracy of peptide binding to I-Ed. J Immunol 155, 2849-57.