Co-supervised by Dr Kirsty Wilson and Professor Katie Flanagan (UTAS). The presence in sera of pro-inflammatory cytokines has emerged as an aetiological and perpetuating factor for major depression across the lifespan. The immune system of the elderly, and particularly females, displays heightened persistent chronic inflammation or ‘inflammaging’. Mechanistically, it may be caused by epigenetic re-programming of monocytes, resulting in an increased capacity to produce inflammatory factors in response to environmental stimuli, such as bacterial and viral toll-like receptor (TLR) ligands.
This re-programming is termed ‘innate immune training’. We propose that the propensity of immune cells to respond by high cytokine production to environmental challenges is mechanistically associated with mood and particularly depression. Recent human trials, including our own, show the immune system may be re-trained away from being prone to produce high levels of pro-inflammatory cytokines using practical interventions such as natural compounds and vaccinations. As an exciting new finding, our pilot studies also show that the diphtheria-tetanus-acellular pertussis (dTap) vaccine in humans induces immune cells capable of dampening inflammation. Aims In this cross-disciplinary study, we will correlate inflammatory status and epigenetic monocyte programming, with depression in young and elderly, and male and female volunteers.
With a view to potential future interventions, we will also test the ‘resilience’ of the innately trained monocytes in the elderly to be reprogrammed away from a pro-inflammatory profile.
Hypotheses:
- Immune biomarkers in blood are associated with subclinical and clinical depression, offering a novel diagnostic correlate, as well as pinpointing new relationships between the brain, the immune system and overall human health.
- Immune profiles and correlates will differ between younger adults and the elderly, and females compared to males. Methods: The laboratory uses world-class big-data ‘omics’ analysis of blood immune cells, including RNAseq, epigenetics, multicolour flowcytometry (up to 27 simultaneous markers on cells), cell sorting, multiplex cytokine analysis (Luminex) as well as classical immunological techniques, e.g. ELISA, ELISPOT, immunohistology, proliferation and functional T cell assays. The PhD candidate: The preferred PhD candidate will have done an Honours or Masters in either immunology, psychology, bioinformatics, biostatistics or a related discipline.
References: [1] Flanagan KL et al. Annu Rev Cell Dev Biol (2017) 33:577. [2] Meyrel M et al. Encephale (2018) 44(1): 67-74.
