Co-supervised by Dr April Kartikasari - plus for specific sub-projects collaboration with Prof Arnan Mitchel and Dr Cesar Huertas (Micro Nano Research Platform) for downstream Lab-on-a-chip practical biomarker detection at home.
Previously, we and others have observed reduced vaccine efficacy in the elderly as well as increased susceptibility to infections and cancers [1]. While age-related immune dysfunction has been extensively studied, underpinning the molecular changes that drive the age-related functional decline of immune cells has proven difficult. Many studies including ours have shown that epigenetic marks including DNA methylation and histone modifications play a fundamental role in determining cell function and identity. These marks are actively modulated by different conditions including stress, lifestyle, sex and age or vaccination [2-3].
This project will systematically map epigenetic changes that promote age-related immune dysfunction, in the context of human vaccination trials, as well as cancer human clinical trials. Specifically, as part of human clinical trial projects, this study will underpin molecular epigenetic mechanisms of immunosenescence that involved in cancer and suboptimal responses to vaccination in the edlerly, and may provide leads for novel therapeutic strategies.
Aims: This project is designed to understand cellular and molecular epigenetic mechanisms involved in both innate and adaptive immunosenescence that cause the decline of immune function. Specifically, this study will uncover age-dependent alterations in epigenetic marks that cause increased incidence of cancer and infections as a consequence of age, utilizing in vitro models, animal models and human clinical trials available in the lab.
Hypotheses:
- Epigenetic mark alterations due to aging promote dysregulation of immune cell function and may contribute to the increased incidence of cancer and infections in old people
- Identification of the changes of epigenetic marks that contribute to the decline of immune function will provide new means of disease prevention and treatment.
Methods: The laboratory uses world-class big-data omics analysis of immune cells, including RNAseq, genome-wide epigenetics, multicolour flowcytometry, cell sorting, multiplex cytokine analysis, as well as classical immunological techniques, e.g. ELISA, ELISPOT, immunohistology, proliferation and functional immune-cell assays.
The PhD candidate: The preferred PhD candidate will have done an Honours or Masters in immunology, vaccines, microbiology, bioinformatics, biostatistics, molecular biology or a related discipline.
References: [1]. Flanagan KL et al. Annu Rev Cell Dev Biol. (2017) 33:577 [2]. Noho-Konteh F et al. Clin Infect Dis. 63 (2016):1213 [3]. Kartikasari et al., EMBO J. 32 (2013): 1393
