Research Overview

For more information about our research, check out Cheryl's 2019 Perspective article in mSystems:

Clonal yet Different: Understanding the Causes of Genomic Heterogeneity in Microbial Species and Impacts on Public Health

mSystems 7;4(3):e00097-19

doi: 10.1128/mSystems.00097-19

We are conceptually-driven rather than taxonomically-driven. Hence, we study a range of bacterial species from different hosts (humans, animals) and environments. If you are interested in any of these research projects, feel free to contact us.

 

Bacteria may be clonal, but strains of the same species are not identical. Strains differ in both allelic and gene content composition. We ask the questions:

  • What makes them different?

  • To what extent are these differences clinically relevant?

• Disease outbreaks

• Disease transmission

• Antibiotic resistance

We use concepts, principles and methods in microbial population genomics, evolutionary biology and bioinformatics to answer these questions.

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Figure credit: Josh Smith

Genomic epidemiology of infectious diseases 

We study the population structure and  dynamics of bacterial pathogens. We use whole genome sequencing to elucidate disease outbreaks, transmission, virulence and the evolution of antimicrobial resistance. Currently, a major project is Staphylococcus aureus that causes bloodstream infections in collaboration with Dr. Isabella Martin (Dartmouth-Hitchcock Medical Center). We also collaborate with the New Hampshire Dept. of Health and Human Services to carry out genomic surveillance of bacterial pathogens that cause food-borne infections (E. coli, Salmonella, Listeria, Campylobacter).

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Staphylococcus on blood agar plates

Horizontal gene transfer and recombination

We study the causes, mechanisms and consequences of gene sharing within and between species.

 

Genetic recombination allows a bacterial cell to rapidly acquire novel traits through incorporation of DNA fragments from other strains or species into its own genome. It can result to either (1) allelic replacements that preserve the size and functionality of the recombined sequence (i.e., similar to “gene conversion” in sexually reproducing organisms) or (2) the addition of new DNA segments when two flanking regions of high DNA similarity initiate the recombination process and mediate successful horizontal gene transfer.

 

The consequences of recombination are vast. It is known to influence a myriad of evolutionary and population processes, including levels of standing diversity, niche expansion, spread of resistance and virulence determinants, and rapid adaptive changes in response to new or fluctuating environmental conditions. It can generate vaccine escape variants and the rapid diversification of surface antigens, allowing immune evasion. Recombination of large DNA segments can also result to the emergence of novel genetic variants or hybrids with unique phenotypes such as multidrug resistance, hyper-virulence and increased transmissibility.

Genomics of host adaptation

In collaboration with the New Hampshire Veterinary Diagnostic Lab, we have collected >1,100 clinical isolates of >20 species of Staphylococcus from >15 wild and domestic animals. Little is known of the evolutionary history of these rare species of Staphylococcus

We also collaborate with Dr. Diana Northup (Univ. of New Mexico) to study Streptomyces bacteria from multiple species of bats.

Streptomyces are prolific producers of bioactive specialized metabolites that have adaptive functions in nature and have found extensive utility in human medicine. They are known as the major source of naturally-derived antibiotics and many pharmaceutically relevant compounds (e.g., antifungals, antitumor, antihelminths, antiprotozoans, immunosuppressants) that we use today.

For both genera, we study their population genome structure and elucidate how  the distribution of their core alleles, accessory genes and mobile genetic elements contribute to their ability to colonize different animal hosts.