PhD Projects » ESR 13: Functional inferences from colinear crAssphage genomes

Host institution:Utrecht University (UU), the Netherlands
Local supervisor: Dr. Bas E. Dutilh (UU, Metagenomics and Genomics)
Local co-supervisor: Dr. Pieter-Jan Haas (University Medical Center Utrecht, Synthetic Microbiology)
Project partner: ESR 11

Viruses related to crAssphage, a bacteriophage discovered by us in 2014,34 are abundant in the intestinal tract of humans around the world. We computationally predicted that crAss-like phages infect Bacteroidetes hosts and this was confirmed when the virus was recently cultured.35 Strikingly, amplification of the virus did not impair the host, but the molecular mechanisms involved remain unknown because the proteins involved in host interaction remain unknown. ESR 13 will focus on identifying host-interaction proteins in crAssphage. We recently discovered that crAss-like phages have been genomically co-linear for millions of years yet encode different proteins in similar genomic contexts.

Based on this collinearity, ESR 13 will

  • extract crAssphage genomes from >10k crAss-positive metagenomic datasets and supplement those with >700 crAssphage genomes from different genera that are already available in our group;
  • measure functional proxies for proteins encoded in a similar genomic context (remote homology, protein folds/sequence motifs, secondary structures, amino acid content, positive and negative selection, phylogenetic profile, gain/loss rates);
  • link the proxies to hosts by assessing functional descriptions of host-interaction proteins in ViralZone phages (ESR 7); and
  • identify strongly supported host-interaction proteins in crAss-like phages.

Significant host-association proteins will be validated at the KU Leuven viromics group by exploiting available human and insect-associated viromes (ESR 11). Thus, we will exploit signals from fundamental processes in genome evolution to predict host-interaction proteins and further our understanding of virus-host interactions.