Into the Vast Unknown: Structure-Function Relationships in Uncharacterized Bacteriophage Proteins

With an estimated global population of 10³¹ particles, bacteriophages (viruses that infect bacterial hosts) are Earth’s most abundant biological entities. Billions of years of evolution have granted phages unparalleled genetic diversity and given rise to a vast collection of genes. We have sequenced and analyzed the genomes of over 3,000 phages and sorted their hundreds of thousands of encoded proteins into phamilies. The functions of over 70% of these protein phamilies are unknown, with a complete dearth of functionally informative sequence-based homology for guidance. We hypothesize that these hypothetical phage proteins represent an unexplored reservoir of genetic, functional, and possibly structural novelty. To address this, we have developed a research pipeline to structurally and functionally characterize subsets of phage-encoded proteins. We have successfully advanced a number of proteins through various stages of this pipeline, which combines bioinformatics, molecular biology, biochemistry and biophysical approaches. This presentation will address our progress on elucidating structure-function relationships in these bacteriophage proteins.