Immunology and Diabetes - Immunogenetics Laboratory headed by Dr Tom Brodnicki

Immunogenetics Laboratory headed by Dr Tom Brodnicki

Research Overview

One of the key challenges in medical research is to elucidate the factors that increase an individual’s risk for developing disease. The focus of my group is identifying how sequence variation for certain genes affects the immune system and increases susceptibility to autoimmune and infectious diseases. It is estimated that autoimmune diseases, such as type 1 diabetes, affect ~4% of the population. During the course of evolution it might be assumed that genetic variation conferring susceptibility for autoimmune disease would undergo negative selection. However, genome-wide association studies and the relatively high prevalence of autoimmune disease suggest that susceptibility alleles are common within the human population. One explanation is that these susceptibility alleles are maintained because they provide resistance to infectious disease. Nevertheless, studying this dichotomy in humans is difficult due to genetic heterogeneity and tissue availability. Instead, mouse models have been widely used to better understand the genetics and disease pathology of infection and autoimmunity. Our principal research strategy is to use the parallel characterization of type 1 diabetes and bacterial infection in mice to facilitate the identification of disease-related genes, as well as determine if bacterial infection can modulate the immune system and potentially prevent autoimmune disease.

Research Themes

How does bacterial infection affect type 1 diabetes susceptibility?

Accelerating disease gene discovery:  Transposon mutagenesis in mice

Genomic and functional analyses of a type 1 diabetes gene

Staff

Dr Tom Brodnicki
Dr Colleen Elso
Leanne Mackin
Michelle Ashton
Nancy Wang
Edward Chu
May Abdulaziz Alsayb
Karolina Novak

Publication Highlights

    1.  J Liu, MP Ashton, H Sumer, MK O’Bryan, TC Brodnicki, PJ Verma (2011) Generation of stable pluripotent stem cells from non-obese diabetic (NOD) mouse tail-tip fibroblasts.  Diabetes  60: 1393-1398

    2.  N Wang, L Mackin, RA Strugnell, O Wijburg, TC Brodnicki (2011) Measuring bacterial load and immune cells in mice infected with Listeria monocytogenes.  Journal of Visual Experiments 54 (http://www.jove.com/details.php?id=3076  doi: 10.3791/3076)

    3.  KLI Tan, L Mackin, N Wang, AT Papenfuss, C Elso, M Ashton, F Quirk, B Phipson, M Bahlo, TP Speed, G Smyth, G Morahan, TC Brodnicki (2010) A recombination hotspot leads to sequence variability within a novel gene (AK005651) and contributes to type 1 diabetes susceptibility.  Genome Research 20: 1629-1638

    4.  Burt RA, L Walkins, IKL Tan, N Wang, L Mackin, F Quirk, P Morgn, J-G Zang, G Morahan, SP Berzins, TC Brodnicki (2010) An NZW-derived interval on chromosome 7 moderates sialadenitis, but not insulitis in NOD mice.  Journal of Immunology 184: 859-868

    5.  MC Jawahar*, TC Brodnicki*, F Quirk, YM Wilson, M Murphy (2008) Behavioural analysis of congenic mouse strains confirms stress-responsive loci on chromosomes 1 and 12.  Behavior Genetics 38:407-416 (*MC Jawahar and TC Brodnicki are co-first authors)

    TC Brodnicki  (2007) Somatic Mutation and Autoimmunity.  Cell 131: 1220-1221

    6.  DKY Ang*, TC Brodnicki*, WE Wilson, P Silveira, BL Gliddon, MA Jordan, AG Baxter, IR van Driel  (2007) Two Genetic Loci Independently Confer Susceptibility to Autoimmune Gastritis.  International Immunology 19: 1135-1144.  (*DKY Ang and TC Brodnicki are co-first authors)

    7.  N Armstrong, TC Brodnicki, TP Speed (2006) Mind the Gap:  Analysis of Marker-Assisted Breeding Strategies for Inbred Mouse Strains.  Mammalian Genome 17: 273-287

    8.  TC Brodnicki, K O’Donnell, F Quirk, DM Tarlinton (2006) Congenic NOD Mouse Strains Fail to Confirm Linkage of a Marginal Zone B Lymphocyte Phenotype to the Idd11 Locus on Chromosome 4.  Journal of Immunology 176: 701-702

    9.  M O’Keeffe, TC Brodnicki, B Fanke, D Vremec, G Morahan, E Maraskovsky, R Steptoe, LC Harrison, K Shortman  (2005) Flt-3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development.  International Immunology 17: 307-314

    10.  TC Brodnicki, F Quirk, G Morahan  (2003) A susceptibility allele from a non-diabetes prone mouse strain accelerates diabetes in NOD congenic mice.  Diabetes 52: 218-222