Rejuvenating immune function through plasmalogen supplementation

Co-supervisors: Dr Sudip Paul and Prof Peter Meikle

Ageing is associated with a progressive decline in immune function, resulting in weaker responses to vaccination, reduced generation of protective immune memory, and increased susceptibility to infection. Changes in cellular lipid metabolism are increasingly recognised as an important feature of immune ageing. Plasmalogens are a major class of ether phospholipids with important roles in membrane organisation, signalling, metabolism, and protection against oxidative stress. Plasmalogen levels decline with age in multiple tissues, raising the possibility that loss of these lipids contributes to impaired immune-cell function. However, whether restoring plasmalogen availability can improve vaccine responses during ageing remains poorly understood.

Testing plasmalogen supplementation as a strategy to improve immune responses during ageing

Our research aims to determine whether dietary plasmalogen precursor supplementation can rejuvenate immune function in aged mice. Using a vaccination model together with state-of-the-art flow cytometry, lipidomics, immunological assays, and molecular approaches, this project will examine how increasing plasmalogen availability influences T- and B-cell responses, antibody production, and immune-cell stress resilience. The study will provide mechanistic insight into the relationship between lipid metabolism and immune ageing and evaluate a potential nutritional strategy for improving vaccine responsiveness in later life.

Research objectives

1. Determine whether plasmalogen supplementation improves vaccine responses in aged mice
   • Compare immune responses following vaccination in aged mice receiving control or plasmalogen precursor-supplemented diets.
   • Assess vaccine-induced antibody responses and determine whether supplementation improves the magnitude and quality of the humoral immune response.
2. Define how plasmalogen supplementation alters cellular immune responses
   • Characterise T-cell and B-cell activation, differentiation, and memory responses in lymphoid tissues following vaccination.
   • Assess key vaccine-responsive populations, including T follicular helper cells, germinal-centre B cells, antibody-secreting cells, and activated T-cell populations.
3. Investigate mechanisms linking plasmalogens to improved immune function
   • Use lipidomics to determine how ageing and supplementation alter plasmalogen and broader lipid profiles in immune cells and tissues.
   • Use proteomics to identify changes in protein expression and biological pathways associated with plasmalogen supplementation and improved immune responses.
   • Integrate lipidomic and proteomic data to identify molecular pathways linking plasmalogen restoration with improved vaccine responses.
   • Investigate whether plasmalogen supplementation improves immune-cell resilience to oxidative stress and lipid peroxidation, and determine how these changes relate to immune activation and vaccine responsiveness.

Your role and opportunities

You will contribute to a translational research program investigating whether lipid supplementation can improve immune function during ageing. Throughout the project, you will:

• Assist with an aged-mouse dietary supplementation and vaccination study.
• Perform immune phenotyping of blood and lymphoid tissues using multicolour flow cytometry.
• Measure vaccine-specific antibody responses and investigate T-cell and B-cell function using immunological assays.
• Learn advanced techniques including lipidomics, proteomics, flow cytometry, ELISA, cell culture, molecular biology, and functional immune assays.
• Analyse immunological, lipidomic and proteomics datasets using statistical and bioinformatic approaches and contribute to scientific publications and conference presentations.