Enigmatic bacterial sphingolipids; elucidating their biosynthesis, transport and function within the host. (360G-Wellcome-333774_Z_25_Z)

Sphingolipids (SLs) play essential roles in membrane structure, cell signalling, and disease pathogenesis in eukaryotic cells. Our understanding of the biosynthesis and function of these enigmatic lipids in higher organisms has been built on decades of research. It was assumed that SL producing bacteria are rare and found in unusual biological niches. However, we discovered that many diverse microbial species have the potential to make SLs. Despite their apparent ubiquity, our existing knowledge of the biosynthesis and function of bacterial SLs is in its infancy. Mounting evidence indicates that SLs are key players in bacterial adaptation and homeostasis within the microbiome. The precise details of the bacterial enzymes that regulate, make and transport SLs are unknown, since they share little homology with their eukaryotic counterparts. Knowledge of how SLs contribute to bacterial fitness and survival within their host is also lacking. Our team will use complementary expertise in structural biology, enzymology, genetics, lipidomics, and bacterial pathogenesis to address two overarching aims: (1) Understand the molecular details of how bacteria make and transport SLs. (2) Characterise what roles bacterial SLs play in host-microbe interactions. Our research will transform the fundamental understanding of bacterial SL biosynthesis and their functional roles in nature.