UKRI/BBSRC-NSF/BIO: The evolutionary transition of host-microbe interactions from commensal symbionts to blood parasites.

Apicomplexans, which include the parasites that cause malaria, include the deadliest eukaryotic pathogens on the planet and have long been assumed to be a parasitic group of organisms that only live within host cells. The story has become more complex, however, with the discovery of apicomplexan lineages, Nephromycidae, which live inside their host without invading cells.

Despite their lifestyle, Nephromyces still features the typical apicomplexan cellular invasion machinery—the apical complex. Nephromyces, therefore, provides an opportunity to understand the ancestral state that served as a platform for the development of major blood pathogens of humans and animals. The research will use a combination of cutting-edge microscopy and genomics to compare the invasion machinery between related virulent pathogens and mutualistic members of Apicomplexa to identify critical elements of pathogen cell invasion.

Outreach to K-12 will be accomplished via a Research Experience for Teachers (RET) fellowship, that will build on previous success engaging high school marine biology teachers and students from inner city Providence. Public outreach will be through a partnership with Art League RI, in which will pair scientists and artists to create exhibits for a series of public engagement events.

How parasites evolve from free-living organisms can provide clues as to key features that can be targeted in therapeutics. Here, a strategy has been devised to characterize the apical complex of the extracellular Nephromyces using single-cell transcriptomics, immuno TEM, and expansion microscopy. These data will be used to perform comparative genomics to reconstruct ancestral features of the intracellular hematozoan cellular invasion and parasitic machineries.

Specifically, the investigators will identify the life cycle stage when the invasion machinery is expressed in Nephromyces extracellular symbionts and reconstruct how the different cell forms linked within its life cycle, determine the structural conservation of the apical complex in Nephromyces as compared to hematozoan blood parasites, and reconstruct the ancestral infection-like processes and other pre-adaptations for parasitism in the Hematozoa. The research will expand taxonomic expertise, through recruitment, retention and mentoring of undergraduate and graduate students, particularly those from underrepresented groups, who will be trained in both modern microscopy and genomic scale techniques.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.