Research

Mobile genetic elements (MGEs) are frequently exchanged between the bacteria in our gut.  We study the molecular mechanisms of horizontal gene flow in the gut Bacteroidales: 

• The phenotypes it mediates

• How the newly acquired gene repertoire incorporates into the recipient cell’s physiology

• How the dynamics of gene exchange can be a driver of the ecology and evolution of the intestinal community

• How these interactions lead to ecosystem properties relevant to human health. 

One of our model systems is a large conjugative plasmid that mediates multi-species biofilm formation in the intestinal community.

Projects:

Plasmid encoded biofilm formation and its importance in community ecology and resilience

While most mobile genetic elements (MGEs) are highly variable, we recently showed that certain conserved MGEs spread through multiple species within individual gut microbiomes. We discovered a large plasmid that enables multi-species biofilm formation in the gut. This plasmid is extraordinary because it has recently spread to people across the globe, becoming ubiquitous, suggesting that it plays a significant role in the gut community and likely human health. We use genetics, bioinformatics, microscopy and experimental evolution to understand how this plasmid shapes our intestinal community.

Identification of bacteriophages that interact with specific MGEs and evaluation of their impact on their cognate MGE’s physiology, ecological and evolutionary dynamics

Bacteriophages (bacterial viruses) are extremely diverse, abundant, ubiquitous, and fast-evolving. Their surface receptors can be encoded within MGEs and they often target surface appendages like those encoded in many MGEs. Bacteria-phage pairs usually engage in antagonistic coevolution where the bacteria evolve resistance (usually at a trade-off), while the phage evolves to overcome these resistance mechanisms. This phenomenon can lead to various dynamics (arms race, continuous fluctuation, bet-hedging), which can significantly impact the gene content, physiological relevance, abundance, ecological and evolutionary dynamics of any prevalent MGE as it spreads. Our current understanding of bacteria-phage dynamics in the intestinal community is primarily derived from computational analyses of metagenomic datasets, with little mechanistic insights. We track experimentally the antagonistic coevolution between phages and this biofilm-formation plasmid, through a molecular and evolutionary lens, to understand its impact on intestinal community ecology.

Analysis of genomic factors that preserve genome integrity to mobile DNA

Gut bacteria must navigate the dangerous minefield of accessing a valuable MGE repertoire while preserving genome integrity. The discovery of CRISPR generated great interest in understanding how bacteria protect themselves from harmful foreign DNA. The Bacteroidales are likely to carry a different and potentially equally rich repertoire of DNA-exclusion systems. Moreover, most of the attention has been devoted to phage exclusion, whereas regulating the acquisition of other sources of foreign DNA probably plays an equally important role in gut bacterial ecology and evolution. We study the genomic determinants of host range and transfer frequency for specific MGEs.  We use high-throughput screening to identify factors that inhibit or increase the frequency of MGE acquisition, as well as mutual exclusion between MGEs.