NOSTER & Science Microbiome Prize winner illuminates how "silent flagellins" from commensal microbiota evade innate immunity

Sara Clasen is the 2023 winner of the NOSTER & Science Microbiome Prize for her work in illuminating how "silent flagellins" from commensal microbiota evade a host's innate immunity.

The NOSTER & Science Microbiome Prize aims to reward innovative research from young investigators working on the functional attributes of the microbiota of any organism that has potential to contribute to our understanding of health and disease, or to guide novel therapeutic interventions.

Strong adaptive immune responses require activation of innate immunity. To do this, innate immune receptors respond to conserved molecules, or ligands, produced by a pathogen. But these ligands are also produced by trillions of microbes that inhabit the gut microbiome – the vast majority of which are nonpathogenic and beneficial to human health. How innate immune receptors tolerate ligands from non-pathogens while recognizing those from pathogens remains poorly understood.

To address this question, Clasen, and her laboratory focused on the Toll-like receptor 5 (TLR5) and its ligand, flagellin. Both pathogenic and commensal bacteria produce flagellins – a crucial protein used to build the filaments used for microbial locomotion. When these filaments break down, they are recognized by TLR5, which binds flagellin and initiates a pro-inflammatory response.

Although this response is well characterized for pathogens like Salmonella, TLR5 response to commensal-derived flagellins remains poorly understood. Clasen identified and characterized the interactions between TLR5 and 40 flagellins that are abundant in the human microbiome and discovered so-called "silent flagellins," which strongly bind but weakly activate TLR5.

According to the findings, unlike pathogen-derived flagellins, these flagellins lack a secondary TLR5 binding site, which mediates their immune receptor response.

"Our discovery of silent flagellins illustrates one way by which innate immune receptors tolerate ligands from commensals," writes Clasen.

Clasen's prize-winning essay will be published in the July 7 issue of Science.

Finalists

Christopher Stewart is a finalist for his essay "Diet-microbe-host interaction in early life: breastmilk bioactives are important to infant microbiome," which focused on the impact of human milk oligosaccharides in maternal milk on the developing infant gut microbiome. Stewart receivedgraduate degrees and a Ph.D. from Northumbria University. After completing a postdoctoral fellowship at Baylor College of Medicine, Steward started his lab in the Translational and Clinical Research Institute at Newcastle University. His research is focused on microbial-host interaction in the gut of infants born premature.

Christoph Thaiss is a finalist for his essay "A microbiome exercise: gut-brain connections drive the motivation to work out," which focused on the microbiome's role in exercise performance and benefits. Thaiss received his undergraduate degrees from the University of Bonn, Y?ale University, and ETH Zürich, and a Ph.D. from the Weizmann Institute of Science. After completing his doctoral training, Thaiss founded his lab in the Microbiology Department of the Perelman School of Medicine at the Unviersity of Pennsylvania where his research focuses on the multifaceted interactions between environmental factors, the gut microbiome, the immune system, metabolism, and the brain.