The Mizrahi group seeks to understand the evolutionary forces that act on microbial genomes, as well as the ecological forces that shape their interaction with their environment. Evolution and genome plasticity are tightly linked to the ecology of a specific organism; therefore, the group studies these specific forces as they occur in nature, with an emphasis on gut environments.
For this purpose, the group uses state of the art tools such as deep sequencing, big data analysis, metabolomics, fluorescence-activated cell sorting (FACS), high-performance microscopy, and classical aerobic and anaerobic microbiology approaches. This knowledge is used, in turn, to understand and influence the role of microbial communities in health and diseases, as well as in agricultural systems. Hence, it is expected to have implications for future developments in food sustainability, renewable energy, and medicine.
Two major directions of research are pursued:
The community assembly dynamics of the microbiome in high temporal and genetic resolution are studied, and they enable the group’s researchers to identify the potential of alternative community states to assemble in gut communities, and thus address basic ecological concepts. As demonstrated in a case in which a certain species preconditions future states of the community as a result of ecological interactions, thereby stimulating the growth of a specific subset of species and inhibiting others. The Mizrahi group maps and studies the microbiome compositional variations that are driven by basic ecological concepts and result in changes in ecosystem function, namely the metabolic efficiency of the microbiome.
Horizontal gene transfer (HGT)
Gut bacterial communities are extremely diverse, complex, and dense, with intricate relationships between the communities and their mammalian host. As such, the immediate proximity and wide range of neighboring cells create a favorable environment for HGT. Plasmids are major mediators of HGT, contributing to genome evolution and the emergence of genetic novelty. Pathogenicity factors, as well as antibiotic-resistance genes, are frequently transferred on plasmids, enabling their rapid spread within a population. Prof. Mizrahi’s fascination with this topic, together with a lack of tools for its study, led the group to develop a metagenomic plasmid isolation and characterization procedure. This pioneering approach provides an overall view of plasmids – their identity, traits, and the phylogenetic diversity of their microbial hosts. They study the importance of HGT in the mammalian gut and the mechanisms by which it occurs, and develop methods for its study. Understanding the role of plasmids as vehicles of genetic information is crucial to our understanding of microbial ecology and evolution.
The aforementioned research directions are studied in real, natural animal and human gut environments; one of the group’s most studied gut ecosystem is the rumen microbiome. A ruminant’s resident microbiome is responsible for most of the food’s digestion and absorption. These microbial communities degrade and ferment the plant fibers, initiating a cascade of fermentation reactions carried out by complex networks of interacting microbial species. By-products of fermentation can be absorbed as nutrients by the animal or be further oxidized by microbes that maximize energy extraction out of them, ultimately leading to the production of carbon dioxide and methane, potent greenhouse gases which dissipate into the atmosphere. There is considerable variation across individual hosts in the way energy flows through the microbiome by alternative pathways for energy conversion involving different species’ composition and metabolic functions; in some cases, as the researchers have recently discovered, these pathways favor or disfavor animal feeding efficiency over methane production. The Mizrahi group brings together microbial genomics, anaerobic microbiology, and microbial community ecology to learn how cooperative or antagonistic ecological interactions between the microbial species that reside in the rumen control the establishment of alternative microbiomes with different functional efficiencies.