Dr. Top's lab is a member of both,
Initiative for Bioinformatics and Evolutionary Studies (IBEST) and Bioinformatics & Computational Biology (BCB).
She also serves as the Director of Graduate Program for BCB.
My research is currently focused on the diversity, evolution and ecology of plasmids that transfer to and replicate in a broad range of bacteria, so-called broad-host-range plasmids. Plasmids are mobile genetic elements found in most bacteria. Because they readily transfer between different types of bacteria under natural conditions, they play an important role in rapid bacterial adaptation to changing environments. A good example is the current epidemic of multiple antibiotic resistance in human pathogens, which is in part due to the spread of multi-drug resistance plasmids. Although plasmid-mediated gene transfer is now recognized as a key mechanism in the alarming rise of antibiotic resistance, little is known about their host range, their ability to invade bacterial populations, and their genetic diversity. The research can be divided up in three main projects.
Plasmid-Host Interaction and Evolution of Plasmid Host-Range
The first one is a collaboration with Dr. Zaid Abdo of the Departments of Mathematics and Statistics, and was recently funded by the National Institutes of Health. Even though rapid plasmid-mediated spread of multi-drug resistance to human pathogens is threatening our ability to fight against infectious diseases, little is known about what determines the range of hosts in which a plasmid can be maintained. Moreover we do not know if and how, and at what tempo that host range can expand, contract or shift over time. Since bacteria evolve very rapidly their drug resistance plasmids can also quickly adapt to novel hosts by reducing their cost and becoming more stable even in the absence of the drugs. The new project aims at discerning patterns of plasmid host range evolution in bacteria through (i) experimental evolution studies followed by (ii) molecular and biochemical analysis of evolved plasmids, and (iii) mathematical and statistical modeling of the evolutionary processes. For example, we found that the stability of a drug resistance plasmid in a novel host can rapidly improve in bacterial populations through mutations in the plasmid alone, the host chromosome alone, or both, and that a single mutation in a plasmid can have a dramatic effect on its host range.
Modeling the Spatial Dynamics of Plasmid Transfer
The goal of the second project is to understand the population dynamics of plasmids in spatially structured bacterial populations. Even though most bacteria in natural and clinical settings form biofilms attached to surfaces such as medical implants and the walls of intestines, little is known about the effect of spatial population structure on the fate of plasmids. We monitor the spread of drug resistance plasmids in biofilms, and collaborator Stephen Krone, Professor of Mathematics, develops mathematical models to predict the spatial dynamics of the transfer and persistence of drug resistance plasmids. This project is funded by the National Institutes of Health.
The Genetic Diversity of Broad-host-Range Plasmids in Bacteria
The third project aims at enhancing our understanding of the diversity and evolutionary history of the extant pool of BHR plasmids. This is done by comparative genomic and phylogenetic analysis of the complete genome sequences of almost 100 plasmids. This project was funded by the National Science Foundation, and the DNA sequencing service has been provided by Department of Energy Joint Genome Institute. Co-investigators are Professors Celeste Brown, Jack Sullivan, and Larry Forney. Future research will focus on the evolutionary history of plasmids: What are the current plasmids' long-term host reservoirs, and do plasmids evolve mostly by vertical descent or through lateral exchange of core genes between plasmids?
A little more,
Views from around the Lab
The research team and their activities in Dr. Top's lab allows University of Idaho undergraduate, graduate students and postdoctoral scientists pursue plasmid research in a professional laboratory environment. Undergraduate students gain experience in a professional laboratory working with other experienced researchers. For more information about the people of Top lab visit the lab members section of this site. a few images from Dr. Top's lab...
Interested in working with us?
Postdoctoral researchers and graduate students who are interested in working on our projects may contact Dr. Top by email. Undergraduates researchers interested in a laboratory internship can also email Dr. Top.
Ready to Apply to Graduate School?
Please go to the UI Department of Biological Sciences Graduate Program page for graduate student application instructions.