How Do Monocytes Remember? Characterisation Of The Early Life Exposures That Induce Innate Immune Memory
- Research Opportunity
- Royal Children’s Hospital/Murdoch Childrens Research Institute
|Mr Boris Novakovicemail@example.com|
|Professor Richard Safferyfirstname.lastname@example.org||+61383416341|
We all know that the adaptive immune system develops memory following specific antigen exposure, but is the same true for the innate immune system? An emerging field of research tells us exactly this, with epigenetic remodelling as the underlying mechanism. Innate immune cells, such as monocytes and macrophages, form this non-specific memory in response to a variety of exogenous signals. Exposure-induced epigenetic remodelling governs their future response to a range of pathogens. This process can be modelled in vitro, using both yeast and bacterial antigens and metabolites (Novakovic et al. Cell 2016), metabolites (Bekkering et al. Cell 2018), vaccines (Arts at el. Cell Host Microbe 2018) and a range of other stimuli.
During pregnancy, both maternal and foetal monocytes show attenuated pro-inflammatory responses correlated with pregnancy-associated hormones. Additionally, foetal monocytes are exposed to a range of environmental factors. We hypothesise that monocytes remodel their chromatin in response to early life environments, which explains their altered function during pregnancy. To test this hypothesis, we will isolate pure monocytes from human blood, and treat them with various stimuli in vitro. After treatment we will measure cytokine release, RNA expression and epigenetic (histone modification) changes. This project is appropriate for students with an interest in molecular biology and immunology and will utilise monocyte isolation and culture, ELISA, chromatin immune-precipitation (ChIP), DNA and RNA extraction and real-time PCR.
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Research NodeRoyal Children’s Hospital/Murdoch Childrens Research Institute
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