How the interactions between species influence each other's evolution

Studying evolution is notoriously difficult because it relies on multiple stochastic processes and the predictable process, natural selection, operates through a genotype to phenotype to fitness map that is riddled with nonadditive interactions like epistasis. An even more difficult challenge is studying coevolution because the evolution of multiple species has to be accounted for, and their evolution depends on one another creating a tangled bank of high order biological interactions. To untangle the bank, we have developed two multispecies laboratory systems that provide experimental control required to build a mechanistic understanding of coevolution.


We have published many papers on coevolution between bacteriophage lambda and its host, Escherichia coli. We are currently interested in using this model system to study how fitness landscapes are deformed during coevolution and how these deformations can set up evolutionary feedbacks that promote innovation.


Microbiome research has proliferated in the last decade. Our role in this area has been to develop a model experimental system to study interactions between metazoan hosts and their microbiomes. The host is a rotifer that has a number of characteristics amenable to microbiome evolution experiments; such as rapid generation time, ease of culturing large population sizes, and it has a rudimentary gut microbiome. We developed this system to learn how hosts coevolve with their microbiomes and to determine how microbiome effects extend beyond their host and into the broader ecosystem.

Viral Speciation

Viral Speciation

Viruses are the most genetically diverse group of organisms on Earth, yet we know little about the processes that drive their diversification. A handful of recent papers have shown that virus diversity can be classified by the Biological Species Concept’s criteria of reproductive isolation. In 2016 we published a paper showing that bacteriophage lambda speciates during the course of laboratory experiments by evolving mechanisms that interfere with strains ability to exchange DNA. We have a number of projects underway on speciation including using high throughput technologies to measure the fitness landscape of speciating bacteriophage lambda, and evolution experiments coupled with mathematical modeling to understand how competition, recombination, and genomic architecture impact speciation. We are also collaborating with Joseph Pogliano to identify traits that cause genetic barriers between viruses in order to understand how viruses in nature speciate.

Protein Evolution

Protein Novelty and Evolvability

In 2018 we published a paper on the molecular mechanism underlying the evolution of bacteriophage lambda to use a new receptor. The key step in lambda’s innovation is evolving a bistable host-recognition protein that folds into multiple conformations; some that use its native receptor and others that bind a new receptor. We are building on this research by 1) performing biochemical and biophysical assays to determine which protein properties cause bistability, 2) teaming up with researchers at UC Berkley and UCLA to test our model on more phages, and 3) analyzing published data to determine how common bistable viruses are. The model also makes predictions for the types of characteristics that promote viral host-rang evolvability that we are testing with evolutionary and synthetic biology experiments.

Phage Therapy

Phage Therapy

We are applying knowledge gained on phage-bacterial coevolution to develop more robust bacteriophage therapeutics. Currently we are designing and testing protocols for evolutionary training, where phages a pre-evolved with bacteria before using them as a therapeutic. This evolutionary training allows the phage to develop counter resistance in order to anticipate and prohibit bacterial evolution. We have shown that this protocol is effective at extending the efficacy of phage at suppressing bacterial populations.

We are also developing gene drives delivered by bacteriophage with the capacity to scrub away antibiotic resistance genes. This work is in collaboration with Ethan Bier and includes microbial experiments, synthetic biology, and mathematical modeling.