We study the experimental evolution of viruses.
Our leading system is Bacteriophage λ, which infects Escherichia coli, however we also study other microbial species. The two-part question that drives the majority of our research is: What mutations cause viruses to gain new functions, such as infecting novel host species. And, what ecological and epidemiological processes promote their evolution.
Our work provides insight into the drivers of emerging diseases, as well as adds to a fundamental understanding of biological evolution. Additionally, our findings are critical for biotechnology that uses viruses to deliver genes or manipulate the microbiome. By knowing how to edit viral genomes to target new or specific cell types, biologists can more precisely make the modifications they intend.
During a typical study we employ a wide range of techniques:
- Experimental microbial evolution
- Genome re-sequencing
- Multiplexed Automated Genome Engineering (MAGE)
Examples of our research
The metaphor of a fitness landscape, where the contours of terrain represent changes in Darwinian fitness, has long been used to visualize evolution by natural selection. Until recently, fitness landscapes were merely metaphors and could not be studied directly. We developed a new, high-throughput method to measure them by combining two technologies, Multiplexed Automated Genome Engineering (MAGE) with next generation sequencing. So far we’ve studied the landscape of the virus λ evolving to exploit a novel receptor, OmpF. With this we can predict the evolution of λ and answer questions about how viruses evolve new functions.
Recently we have become interested in finding genomic signatures of disease emergence. We’d like to know if there are molecular tells for whether or not a viral population is about to switch hosts. Knowing these will provide key insight into viral evolution and provide tools to survey problematic viral populations. To do this we intend on running hundreds of viral evolution experiments that we will analyze with genome re-sequencing and bioinformatics.
We have teamed up with William Cramer’s group at Purdue University to study the physics of λ binding to a new receptor, OmpF. Cramer's group is able to track the dynamics of single molecule interactions between the phage and its receptor. This investigation will reveal the mechanism by which viruses target new receptors, and more generally it will help us understand the evolutionary steps required for novel protein interactions to evolve.
As we have become more adept at using synthetic biology technology to perform evolution experiments (see section on fitness landscapes), we’ve developed a side interest in improving this technology. We are now taking an orthogonal approach, instead of using synthetic biology to study evolution, we’re using principals of evolution to improve the technology.
Evolutionary and synthetic biology have very different origins, and are often housed in separate academic departments, however as we move between the two its become obvious that they have significant conceptual and practical overlap. Each is concerned with editing genomes, one governed by the invisible hand of natural selection, and the second by the gloved hand of researchers. This connection creates a powerful synergy.