About Dr Chris Jolly

I aim to understand how antibody hypermutation (the process by which lymphoid B cells evolve the antibodies they produce in response to infection from low affinity into high affinity in just a few days) is regulated, and how off-target hypermutation induces B cell cancers.

Using the enzyme AID, immune B cells mutate their antibody genes at extremely high rates during infections, to produce, then select antibodies best able to neutralise the infecting pathogen. This process is essentially Darwinian evolution of somatic B cells in extreme fast motion. Unfortunately, mutation of "off-target" genes by AID induces B cell cancers. My group seeks to understand why AID-induced DNA damage leads to mutation and cancer, when similar DNA damage is generally repaired faithfully. We use unique transgenic mouse models to dissect the DNA repair pathways involved in antibody hypermutation, and to dissect the role of the cell cycle in the process.

After a productive period of PhD studies in Sydney characterising novel proteins responsible for both innate immunity in wheat grains ("defensins", related to vertebrate chemokines) and for wheat grain commercial quality (>250 citations), I changed my research focus to mechanisms of oncogenesis in lymphocytes. I studied the role of retroviruses in T cell leukemias with Dr Helen O’Neill at the John Curtin School of Medical Research (ANU). In 1994, I was offered a position as a postdoctoral fellow at the MRC Laboratory of Molecular Biology, in Cambridge, UK, working with Michael Neuberger on antibody hypermutation, the mechanism of which was then completely unknown. In 1998, I returned to Sydney, joining the Centenary Institute at the University of Sydney to start the DNA Repair research group. The DNA Repair Group has published in very high impact journals such as Immunity and J Exp Med, as well as in respected specialist journals such as Nucleic Acids Res and J Immunol (>500 citations), maintaining continuous NHMRC funding since 2001.

Selected publications

Selected Publications
Chan, T.D., K. Wood, J.R. Hermes, D. Butt, C.J. Jolly, A. Basten, and R. Brink. 2012. Elimination of germinal center-derived self-reactive B cells is governed by the location and level of self-antigen. Immunity 37:893-904. 

Sharbeen, G., C.W. Yee, A.L. Smith, and C.J. Jolly. 2012. Ectopic restriction of DNA repair reveals that UNG2 excises AID-induced uracils predominantly or exclusively during G1 phase. J. Exp. Med. 209:965-974.

Sharbeen, G., A.J. Cook, K.K. Lau, J. Raftery, C.W. Yee, and C.J. Jolly. 2010. Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo. Nucleic Acids Res. 38:8120-8130.

Jolly, C.J., A.J. Cook, and J.P. Manis. 2008. Fixing DNA breaks during class switch recombination. J Exp Med. 205:509-513.

Cook, A.J., J.M. Raftery, K.K. Lau, A. Jessup, R.S. Harris, S. Takeda, and C.J. Jolly. 2007. DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion. PLoS Biol. 5:792-799.

Cook, A.J.L., L. Oganesian, P. Harumal, A. Basten, R. Brink, and C.J. Jolly. 2003. Reduced Switching in SCID B Cells Is Associated with Altered Somatic Mutation of Recombined S Regions. J Immunol. 171:6556-6564.

Jolly, C.J., and M.S. Neuberger. 2001. Somatic hypermutation of immunoglobulin kappa transgenes: association of mutability with demethylation. Immunol. Cell Biol. 79:18-22.

Williams*, G.T., C.J. Jolly*, J. Kohler, and M.S. Neuberger. 2000. The contribution of somatic hypermutation to the diversity of serum immunoglobulin: dramatic increase with age. Immunity. 13:409-417. IF2010=21.637 *joint first authors

Klix, N., C.J. Jolly, S.L. Davies, M. Bruggemann, G.T. Williams, and M.S. Neuberger. 1998. Multiple sequences from downstream of the J kappa cluster can combine to recruit somatic hypermutation to a heterologous, upstream mutation domain. Eur. J. Immunol. 28:317-326.

Jolly, C.J., N. Klix, and M.S. Neuberger. 1997. Rapid methods for the analysis of immunoglobulin gene hypermutation: application to transgenic and gene targeted mice. Nucleic Acids Res. 25:1913-1919.

Jolly C.J., Wagner S, Rada C, Klix N, Milstein C, and Neuberger, MS (1996) The targeting of somatic hypermutation. Semin Immunol 8: 159-168. 

Jolly CJ, Glenn GM, Rahman S (1996) GSP-1 genes are linked to the grain hardness locus (H alpha) on wheat chromosome 5D. Proc Nat Acad Sci USA 93: 2408-2413.