Exploring the contribution of intrinsic lipids to immune cell development and function

Research Opportunity
PhD students, Honours students
Number of Honour Places Available
2
Department / Centre
Baker Department of Cardiometabolic Health
Location
Baker Heart and Diabetes Institute
Primary Supervisor Email Number Webpage
Professor Andrew Murphy andrew.murphy@baker.edu.au 02 8532 1292
Co-supervisor Email Number Webpage
Doctor Graeme Lancaster graeme.lancaster@baker.edu.au

Summary This project is focused on exploring how unique lipid signatures (lipidomes) of immune cells influence their function and/or development. The overarching goal is to identify ways to manipulate specific lipids to alter cell function in disease.

Project Details

Over the past few years we have generated a new and exciting data set profiling the lipid compositions (lipidome) of 16 different human immune cells and the major mouse immune cell equivalents. This revealed striking diversity between various immune cells, particularly between the innate and adaptive immune system.

We are now exploring two overall questions: 1. Do specific lipids drive immune cell function? 2. How do the lipidomes of immune cells form as they develop from stem cells.

The specific project can be focused on either of the two questions above.

Project 1: Exploring the contribution of lipids sensitive to peroxidation which confer susceptibility to a specific form of cell death known as ferroptosis.

Hypothesis: Immune cells enriched in lipids that are sensitive to peroxidation undergo ferroptosis when exposed to ferroptotic agonists, while immune cells devoid in these lipids will be resistant.

This project will involve manipulating human and mouse immune cells in culture. Techniques to explore this question will be cell death assays via flow cytometry and assessment of lipid peroxidation by mass spectrometry. Mouse models will also be used to test this hypothesis in vivo and depending on the applicant (hons/PhD) will use mouse models to genetically modify the lipid composition or ferroptotic pathway of specific immune cells.

Project 2: Determining the contribution of particular lipids to immune cell development.

Hypothesis: Specific lipids are critical to the development of immune cells

This project will determine the lipidomes of haematopoietic stem cells and how they change as these cells mature down specific lineages to form mature immune cells. Given we have identified a very unique signature in blood neutrophils (i.e. an enrichment in ether lipids), this project will first explore what happens when we delete an enzyme called glyceronephosphate O-acyltransferase (GNPAT – rate limiting enzyme for the production of ether lipids) specifically in stem cells and explore the neutrophil maturation pathway in the bone marrow and blood. We will also explore some functional properties of neutrophils such as inflammatory signalling in response to bacterial stimuli and phagocytosis. These experiments will be conducted in mice using flow cytometry to quantify cell population and examine the functional readouts.



Faculty Research Themes

School Research Themes

Cardiometabolic



Research Opportunities

PhD students, Honours 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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