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Viral Evolution

 

 

 

 

 

 

 

 

 

 

Viruses that infect bacteria ("bacteriophages" or "phages") are easily and safely manipulated in lab, and evolve extraordinarily quickly. Moreover, their entire genomes can be sequenced. They are thus excellent model systems for resolving evolutionary questions, especially those posed by viral pathogens. Students in the Viral Evolution stream experience evolution not as an abstract historical idea, but as a concrete, measurable process that will take place on their lab benches over the course of days or weeks. They use a variety of common molecular and microbiological techniques while learning evolutionary concepts that will be important to careers in biology and/or public health.

The stream ties together a variety of studies which use mostly similar techniques but answer very different sorts of questions. These studies involve a high degree of both collaboration and independent thought, and can be extended in various directions depending on the interests and input of students. Students learn how to grow bacteria and phage populations, perform PCR, run and visualize gels, clean and precipitate DNA, sequence, perform basic statistical analyses, and use a variety of other methods depending on their projects. They get frequent intermediate results that help them determine how well their project and methods are working, and learn to flexibly optimize protocols and revise hypotheses in response to these results.

The Viral Evolution stream applies the Bull lab’s extensive background in experimental viral evolution. In some cases the proposed studies break entirely new ground, while in other cases they replicate previously completed studies in different systems or different conditions. In all cases, however, they are intended to yield publishable studies that will be of interest to evolutionary biologists, epidemiologists, and/or microbiologists.

Students are working on five different projects. Many of the projects can be extended indefinitely or will open up further questions to be answered. These projects are directly within the Bull lab’s core competencies and interests. In fact, some were originally planned as projects for the Bull lab proper.


Host Adaptation. How much specialization occurs during adaptation of T7 virus to new hosts or hosts in different physiological states? This is relevant to understanding the limits of adaptation and how quickly viruses (such as bird flu) will adapt to new hosts.

Mutation-prone virus. Mutations provide variation needed for evolution, but most are harmful. We are adapting T7 with a partially deleted DNA polymerase that makes many mistakes to determine if the high mutation rate decreases and/or how the virus evolves to deal with the excess mutations.

Messy protein synthesis. A particular DNA sequence generally results in a particular protein. However, with an error-prone RNA polymerase, many proteins may contain mistakes that cause misfolding or loss of function. We are adapting a T7 under these conditions to determine if this selects for changes in gene expression, or proteins that are more stable when mutated.

Genomic Interactions. We are adapting a T7 line in which one gene is replaced by a gene from a different virus. We will then see how the virus compensates to recover from this perturbation. This has implications for engineering genomes for industry.

Testing optimality model predictions.
Evolutionary theory predicts how organisms “should” evolve to maximize reproduction, but these predictions may be wrong due to unanticipated constraints. Students are testing if SP6 virus (related to T7) evolves according to the predictions of a model similar to one used to predict the evolution of virulence in human viruses.

 

Stream Faculty:
• Dr. James Bull


Research Educator:
• Dr. Rick Heineman
(heineman@mail.utexas.edu)

School of Biological Sciences Website:http://www.biosci.utexas.edu/

Spring: Gives BIO 205L or CH 204 Credit.
Fall: Gives BIO 377 or CH 369K Credit.

 

Figure 1. T7 bacteriophage, my primary model system.: (T7 Bacteriophage DNA and Protein Imaging.  Tara Spires and R. Malcolm Brown, Jr. Department of Botany, The University of Texas at Austin, Austin, Tx., 78713)Figure 1. T7 bacteriophage, my primary model system.: (T7 Bacteriophage DNA and Protein Imaging. Tara Spires and R. Malcolm Brown, Jr. Department of Botany, The University of Texas at Austin, Austin, Tx., 78713)

 

Figure 2.  Darth Phager.: Artist's conception of a phage, drawn by student Justin Hsu.Figure 2. Darth Phager.: Artist's conception of a phage, drawn by student Justin Hsu.