Research Interests
Microbial Molecular Evolution and Ecology
I have a broad set of research interests that range from studies of experimental
evolution of microbes to developing novel antimicrobials and redefining
the microbial species concept. What unites this disparate set of topics
is the use of molecular and experimental methods to study the processes
and patterns of microbial ecology and evolution.
Gene Trees, Genomics and a Microbial Species Concept.
The goal of this
work is to evaluate the core genome hypothesis, which posits that there
is a core set of shared genes that define a microbial species. Although
it is clear that mechanisms exist for abundant and widespread genetic
transfer between microbial lineages, the observation of phenotypic clustering
argues for genomic stability and cohesion. To evaluate the importance
of genomic and evolutionary stability versus genomic flux, we employ population
and comparative genomic methods. The following questions are addressed
by these data:
- Is there a shared, core genome that defines a bacterial species?
- What fraction of the genome is core versus auxiliary?
- How are core and auxiliary genes distributed along the chromosome?
- Do core genes experience elevated levels of divergence compared to
auxiliary genes, as predicted by the core genome hypothesis?
- Do taxa cluster based on genome-level information in the same manner
as they do based on phenotype?
Evolution of Antibiotic Resistance
What we know about the origin and
evolution of antibiotic resistance has been learned almost exclusively from studies of
clinical isolates of human pathogens. Little attention has been paid to the immense reservoirs
of resistance genes segregating in natural populations. Our studies focus on determining the
origin and evolution of resistance mechanisms in natural isolates of bacteria obtained from
wild mammals and environmental settings, assess the fitness of "natural" versus "clinical"
resistance mechanisms and incorporate these data into existing epidemiological models that
dictate therapeutic treatments. Such data are critical to our efforts to design more
"resistible" antibiotics and to predict future pathways of resistance evolution.
Evolution of Microbial Defense Systems
The goal of this work is to explore issues regarding the origin and evolutionary
diversification of microbial defense systems (such as antibiotics, bacteriocins, etc.)
in bacterial populations and communities, as well as the evolutionary response to their
presence, both in terms of the evolution of resistance and the further diversification of
bacteriocins (the evolutionary arms-race). We employ methods of molecular phylogenetics,
population genetics and experimental evolution to evaluate the patterns and process of
bacteriocin evolution across the diversity of microbes.
Molecular Ecology of Bacteriocins
We have developed in silico, in vitro and in vivo experimental models that permit us to
explore the ecological role of microbial defense systems under a variety of environmental
settings. Recent work has focused on establishing a mouse model to permit examination of
the role of bacteriocins in mediating the dynamics of bacterial interactions in a more natural
setting, the mouse colon. These studies have revealed that microbial defense systems may
play an important role in the generation and maintenance of biological diversity.
Molecular Evolution of Experimental Populations
Dr. Richard Lenski and his colleagues at MSU have evolved replicate populations of E. coli
for over 20,000 generations in their laboratory. These lineages have allowed a detailed
investigation into the dynamics of phenotypic evolution, including changes in ecological
competitiveness, morphology and physiology. We are working, in collaboration with the Lenski
lab, to extend these investigations to the molecular level. The following questions are
addressed by our molecular analysis:
- What is the actual rate of DNA sequence evolution when the time of divergence is known exactly?
- What are the relative proportions of the various classes of mutations?
- How concordant are rates of molecular and phenotypic evolution?
- Do we observe parallel molecular evolution in replicate lines?
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