Probing immune sex differences through transcriptomics and epigenetics
With sex differences widely documented to play a significant role in the immune response, we are looking to further investigate the poorly understood impact of sex differences on the developing immune system through a close collaboration with Alex Shalek at MIT, being the first group to bring their portable low cost single-cell RNA-seq Seq-well platform to the UK. This work, led by Nicholas Lim, looks to analyse single-cell transcriptomic profiles of cord blood mononuclear cells from HIV-unexposed and HIV-exposed sex-discordant twins to elucidate the contribution of biological sex to the neonatal immune response in the presence of HIV at an unprecedented resolution.
To explore the impact of epigenetics on differential immune gene expression we are collaborating with Veron Ramsuran at the University of KwaZulu-Natal to compare the methylation patterns of immune genes in mononuclear cord blood cells from sex-discordant twins, Previous studies have shown that males have five-fold more methylated autosomal CpG sites than females, the majority of which are acquired in-utero and maintained long-term. We are currently exploring the role of androgens in mediating these striking epigenetic differences. The main sex hormone difference between male and female foetuses is greater androgen synthesis in males, and previous studies suggest that androgens are likely to contribute to the substantial sex differences observed in autosomal DNA methylation in early life.