Associate Professor Robyn Slattery

Current Position:
Associate Professor

Phone:
+ 61 3 9903 0075

Facsimile:
+ 61 3 9903 0018

Email:
robyn.slattery@med.monash.edu.au

Office:
2U27, Department of Immunology
Level 2, Monash University Building, AMREP
Commercial Road
Melbourne 3004

Laboratory:
2U25, Department of Immunology
Level 2, Monash University Building, AMREP
Commercial Road
Melbourne 3004

Biosketch:
Dr. Robyn Slattery completed a PhD with Prof JFAP Miller at the Walter & Eliza Hall Institute (WEHI) in 1991 on "The role of MHC in type 1 Diabetes". She then spent one year as a post doctoral fellow at WEHI, followed by 2 years as a post doctoral fellow at DNAX Research Institute in Palo Alto, California working in the field of tissue specific genetic engineering. In 1994 she returned to Australia to run her own laboratory, utilizing novel genetic engineering techniques to investigate the role of susceptibility genes in Type 1 Diabetes (T1D), at the John Curtin School of Medical Research, Australian National University, Canberra. In 2004 she relocated to Melbourne to accept a position as Associate Professor in the Department of Immunology, where she continues to study the immunogenetics of T1D. She has a major involvement in the teaching of immunology to undergraduate, honours & postgraduate students.

Current Research Focus:
Type 1 diabetes (T1D) in both humans and NOD mice results from T cell mediated autoimmune destruction of insulin producing pancreatic ß cells. Linkage studies have shown that T1D in NOD mice is a polygenic disease involving more than 19 chromosomal susceptibility regions. Our research group is interested in studying three of these susceptibility regions Idd1 (the MHC) Idd2 (the insulin promoter) and Idd13 (recently identified by our group as ß2M).

Idd1 Our group utilizes the cre/lox recombination system in NOD mice to understand the role of the MHC genes in diabetes. This system allows us to remove MHC genes from specific tissues while leaving these genes expressed normally in other tissues. We have thus far created a panel of cre NOD mice that allow us to delete MHC expression from either the target beta cells, or different subpopulations of the immune system.

Idd2 Recently our group identified some unique mutations in the human insulin promoter that control the expression of insulin to different cell types. This is being investigated for its role in predisposing to type 1 diabetes.

Idd13 Despite extensive investigation, the identification of individual susceptibility genes either within or outside the major histocompatibility (MHC) region has proven problematic due to the limitations of linkage analysis. We recently provided the first unequivocal identification of a single diabetes susceptibility gene, which lies outside the MHC region. Using allelic reconstitution by transgenic rescue we showed that NOD mice expressing the ß2Ma allele developed diabetes whereas NOD mice expressing the ß2Mb allele were protected. The murine ß2Ma allele differs from the ß2Mb allele only at a single amino acid. The mechanism of susceptibility and resistance conferred by ß2M has not been elucidated. In particular, it is not known how such a small change in ß2M could confer such a dramatic alteration in the immune response to islet tissue. It is not known which cell types impart ß2M mediated resistance and susceptibility to T1D. Utilizing the ß2Ma (susceptible) and ß2Mb (resistant) transgenic mice it will be possible to dissect out the role of different cell populations in the thymus, and in the periphery, which confer ß2M isoform mediated protection and susceptibility. Likewise, utilizing the tissue specific knock-out NOD mice which have specific deletions of ß2M in both the insulin producing beta cells (HIPcre) and in the antigen presenting cells of the thymus and the periphery (PIEcre) it will be possible to assess the role of tissue specific expression of ß2M in conferring susceptibility. Relevance to type 1 diabetics: Our understanding of the role of ß2M and MHC in directing the autoimmune response is crucial to an understanding of how to regulate the disease in predisposed individuals. Early identification of patients, through genetic markers such as those we have identified in Idd2, , will give us a therapeutic window before the onset of diabetes in which to immunomodulate at-risk individuals.

Selected Publications:
S L Snelgrove, J de Jersey, SE. Palmer, S Teteris, A Mullbacher3 JFAP Miller4 and Slattery RM. Beta cells cannot directly prime diabetogenic CD8 T cells in non-obese diabetic mice. Proc Natl Acad Sci. Proc Natl Acad Sci U S A. 2007;104(4):1295-300

Serreze DV, Holl TM, Marron MP, Graser RT, Johnson EA, Choisy-Rossi C, Slattery RM, Lieberman SM, DiLorenzo TP. MHC class II molecules play a role in the selection of autoreactive class I-restricted CD8 T cells that are essential contributors to type 1 diabetes development in nonobese diabetic mice. J Immunol. 2004 Jan 15;172(2):871-9.

Hamilton-Williams EE, Palmer SE, Charlton B, Slattery RM (2003). Beta cell MHC class I is a late requirement for diabetes. Proc Natl Acad Sci USA 100, 6688-6693.

Silva D, Petrovsky N, Socha L, Slattery R, Gatenby P, Charlton B (2003).Mechanisms of accelerated immune-mediated diabetes resulting from islet beta-cell expression of a FAS ligand transgene. J Immunol. 170, 4996-5002

Petrovsky N, Silva D, Socha L, Slattery R, Charlton B. The role of Fas ligand in beta cell destruction in autoimmune diabetes of NOD mice. Ann N Y Acad Sci. 2002 Apr;958:204-8.

Hamilton-Williams EE, Serreze DV, Charlton B, Johnson EA, Marron MP, Mullbacher A, Slattery RM. (2001). Beta2-microglobulin identified as a diabetes susceptibility gene in NOD mice. Proc. Natl. Acad. Sci. USA 98, 11533-11538.

Charlton B, Zhang MD, Slattery RM. B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice. Immunol Cell Biol. 2001 Dec;79(6):597-601.

Charlton B, Fathman CG, Slattery RM ( 1998). Th1 unresponsiveness can be infectious for unrelated antigens. Immunol Cell Biol 76 (2),173-178

Hogan SP, Foster PS, Charlton B, Slattery RM. (1998). Prevention of Th2-mediated murine allergic airways disease by soluble antigen administration in the neonate Proc Natl.Acad. Sci.USA 95 (5), 2441-2445

Pritchard CA, Bolin L, Slattery R, et al.( 1996). Post-natal lethality and neurological and gastrointestinal defects in mice with targeted disruption of the A-Raf protein kinase gene. Curr. Biol 6 (5): 614-617