Trained immunity in the early life programming of complex disease
Epigenetics Research, Murdoch Children’s Research Institute, and Department of Paediatrics, University of Melbourne, Parkville, Australia
We apply a range of epigenetic and other molecular and cellular techniques to a unique collection of longitudinal human birth cohorts and clinical trials in order to understand the relationship between genetics, epigenetic (and other) molecular mediators and environmental exposures in modifying the risk of non-communicable disease.
Trained immunity in early life and complex human disease
We recently discovered that monocytes of food allergic children show a hyper-inflammatory phenotype at birth and 12 months of age. We also found inherent functional deficits in naive T-cells in food allergic children. We are currently investigating the epigenetic processes underlying food allergy in human monocytes and T-cells from the HealthNuts and VITALITY cohort studies. We are also examining the role of TRIM in other complex conditions, such as Gestational Diabetes Mellitus (GDM) and obesity, using a range of Australian-based cohorts, including the Barwon Infant Study, PETS and PIES.
Epigenetics in vaccine induced trained immunity
Epidemiological evidence suggests that the beneficial non-specific effects of the BCG (Bcil) vaccine last at least 5 years, which implies the role of long term epigenetic memory. One explanation for the heterologoues effects of BCG vaccine is through the induction of TRIM, which has been demonstrated in human monocytes in vivo and ex vivo, as well as bone marrow progenitors in mice. In collaboration with Professor Nigel Curtis, Katie Flanagan and Mihai Netea we are performing the first EWAS (Epigenome-Wide Association Study) of TRIM, using samples from the MIS-BAIR clinical trial.
· Richard Saffery, PhD, Professor and Epigenetics Group Leader
· Boris Novakovic, PhD, Senior Research Fellow and Team Leader
· Line Hjort, PhD, Postdoctoral Fellow
· Melanie Neeland, PhD, Postdoctoral Fellow
· Samira Imran, PhD student
· Toby Mansell, PhD student
· Rebecca Shepherd, Masters student
· Sachintha Wijegunasekara, Honours Student
· Bowon Kim, Research Assistant
· Anna Czajko, Lab Manager
· Novakovic et al. (2016) Cell. PMID: 27863248
· Arts et al. (2016) Cell Metabolism. PMID: 27866838
· Bekkering et al. (2018) Cell. PMID: 29328908
· Dominguez-Andres et al. (2018) Cell Metabolism. PMID: 30293776
· Novakovic et al. (2019) Nature Communications.
· Hjort et al. (2019) Lancet Diabetes and Endocrinology. PMID: 31128973
· Arts et al. (2018) Cell Host Microbe. PMID: 29324233
· Neeland et al. (2018) Journal of Allergy and Clinical Immunology. PMID: 29154959
· Martino et al. (2018) Nature Communications. PMID: 30120223
· Zhang et al. (2016) Science Translational Medicine. PMID: 26764159