Type I interferon as a novel endogenous trigger of trained immunity

Research Opportunity: PhD students
Department / Centre: Baker Department of Cardiometabolic Health
Location: Baker Heart and Diabetes Institute

Primary Supervisor	Email	Number	Webpage
Dr Andrew Fleetwood	andrew.fleetwood@unimelb.edu.au		Personal web page

Co-supervisor	Email	Number	Webpage
A/Professor Andrew Murphy			Personal web page

Summary Trained immunity is a form of innate immune memory resulting in a “high-alert” immune state. We will explore whether type I interferon can build immunological memory in vivo and whether this exerts harmful effects in the setting of chronic inflammation, such as atherosclerosis.

Project Details

Immune memory is a defining feature of the adaptive immune system, but activation of the innate immune system can also result in heightened responses to re-challenge. This adaptation has been termed "trained immunity", a de facto form of innate immune memory. Studies over the past few years have pointed to the broad benefits of trained immunity for host defence but have also suggested detrimental outcomes in chronic inflammatory disease, such as atherosclerosis.

By inducing metabolic and epigenetic changes in hematopoietic stem cells (HSCs), trained immunity drives myeloid cell expansion and the sustained generation of monocytes with a “proinflammatory” phenotype.

We have identified type I interferon as a novel endogenous signal of trained immunity in vitro. This proposal will extend these studies and explore whether type I interferon drives trained immunity in vivo, and whether this effect promotes detrimental outcomes in chronic inflammatory conditions, such as cardiovascular disease. This project aims to identify, characterize and manipulate the metabolic, epigenetic and transcriptional pathways responsible for type I interferon training in myeloid cells and their precursors. Furthermore, this project aims to determine whether type I interferon training exerts helpful or harmful effects in different disease settings. Identifying and characterizing a new endogenous trigger of trained immunity will greatly strengthen our capacity to develop novel strategies to target this complex immune phenomenon.

Techniques: You will acquire a wide-range of skills in animal models, cell biology and molecular biology including primary human and mouse macrophage culture, ELISA assays, metabolic readouts, enzymatic assays, flow cytometry, Western blotting, Real‐Time PCR.

Faculty Research Themes

School Research Themes

Cardiometabolic

Research Opportunities

PhD students
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre

Baker Department of Cardiometabolic Health

Research Node

Baker Heart and Diabetes Institute

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