Many insects have more consequential associations with bacteria than we have with the human microbiome. We create genetic tools to study these bacterial symbionts and engineer their interactions with insects. We also use experimental evolution to examine how new symbionts arise and how interactions within a microbiome and between microbes and their hosts can change. These projects are highly collaborative and have involved researchers from the Moran Lab, the Davies Lab, the Ellington Lab and other research groups.

Current Funding: ARO MURI, NSF EDGE, USDA NIFA
Past Funding: DARPA BRICS, DARPA Insect Allies, ERDC

Overview Publication

• Elston et al. (2022) Trends in Microbiology PMID: 34103228

Honey Bees: Functional Genomics and Protecting Pollinator Health

Aphids: Understanding the Evolution of Endosymbionts and Pest Control

Improving the Reliability of Synthetic Biology

Synthetic biology applies engineering principles to create living systems with predictable and useful behaviors from collections of standardized genetic parts. However, living systems – unlike mechanical devices – inevitably evolve when their DNA sequences accumulate copying errors, often resulting in "broken" cells that no longer function as they were programmed. We are addressing this challenge by better characterizing how engineered cells evolve and using this information to design DNA sequences and host cells that are more robust against unwanted evolution. Also, precisely defining the function, extent, and provenance of genetic parts can be complicated because variation in these parts can arise from engineering or intentional evolution. This work includes: (1) developing "negative design" software to alert researchers to genetically unstable and unintentionally burdensome DNA designs; (2) using experimental evolution and engineering to create "antimutator" variants of host organisms that have lower-than-natural mutation rates; and (3) developing databases and software tools for improved annotation of engineered DNA sequences and common variants of those sequences.

Current Researchers: Dennis Mishler, Cameron Roots

Representative Publications

• Radde et al. (2024) Nature Communications PMID: 39048554
• Roots & Barrick (2024) Synthetic Biology PMID: 39722801
• McGuffie & Barrick (2021) Nucleic Acids Research PMID: 34019636
• Deatherage et al. (2018) Nucleic Acids Research PMID: 30137492
• Jack et al. (2015) ACS Synthetic Biology PMID:26096262

Current Funding: NIH R01;     Past Funding: NSF CAREER, DARPA BRICS, DARPA Insect Allies

Dynamics of Microbial Genome Evolution

The E. coli Long-Term Evolution Experiment (LTEE)

We develop the breseq computational pipeline for identifying mutations in laboratory-evolved microbial genomes from next-generation sequencing data. We have used this tool to extensively study rates of genome evolution in the >35-year Lenski long-term evolution experiment (LTEE) with E. coli. We continue to develop breseq and related computational pipelines so that it can be used for more additional applications related to strain engineering and medicine. For example, we are interested in how tracking rare variants within populations of microorganisms can anticipate further evolutionary trajectories and how this information might be used to better diagnose and treat disease. We also have other ongoing projects related to understanding the mechanisms and dynamics of bacterial evolution and ecology in the LTEE using other high-throughput and systems biology approaches.

Current Researchers: Alexa Morton, Pranesh Rao, Ira Zibbu

News: Legendary bacterial evolution experiment enters new era

Representative Publications

• Deatherage & Barrick et al. (2021) Cell Systems PMID: 34536379
• Zhang et al. (2019) Nature Communications PMID: 31863068
• Deatherage et al. (2017) PNAS PMID: 28202733
• Deatherage and Barrick (2014) Methods Mol in Molecular Biology PMID:24838886
• Barrick and Lenski (2013) Nature Reviews Genetics. PMID:24166031

Funding: NSF LTREB, UT-CNS SPARK, NSF EEID, NASA     Past Funding: NSF K99/R00

Evolution and Engineering of Naturally Transformable Bacteria

Naturally competent bacteria have expanded evolutionary potential because they can readily acquire new DNA from their environment. We are using experimental evolution of the model organism Acinetobacter baylyi ADP1 to understand how horizontally acquired genes and mobile genetic elements become domesticated after their incorporation into a new genome and the broader effects of gene acquisition on the rest of the genome. We are also studying the role of chemical specificity in determining the fate of acquired DNA as either nutrition or genetic information. These bacteria also provide an improved platform for studying microbial genome engineering due to the ease of reconstructing mutations and introducing new genes. We are investigating sources of genetic instability in ADP1 and engineering a clean genome version of this strain by deleting transposable elements and prophages. This will promote the use of ADP1 in synthetic biology by reducing rates of mutations that lead to inactivation of introduced genes. Further, we are using ADP1 as a platform to understand the limits to streamlining bacterial genomes and identifying adaptations to overcome the fitness costs of reduced genomes.

Current Researchers: Isaac Gifford, Meghna Vergis

Representative Publications

• Gifford et al. (2020) PLoS Genetics PMID:32232367
• Suárez et al. (2020) Nucleic Acids Research PMID:32232367
• Suárez et al. (2017) Applied and Environmental Microbiology PMID:28667117
• Renda et al. (2015) Journal of Bacteriology PMID:25512307

Funding: NSF, UT-CNS SPARK     Past Funding: Welch Foundation, NSF CAREER

Evolution and Ecology of Bartonella Parasites in the Negev Desert

Bartonella are diverse blood-borne parasites that can cause zoonotic infections of humans. The Hawlena Lab studies Bartonella species that circulate in gerbil populations in the Negev Desert in southwestern Israel. In these natural wildlife communities, multiple species of Bartonella infect and co-infect multiple host species, making it a dynamic system for studying host-parasite interactions. Our laboratory collaborates on projects characterizing how the genomes of these Bartonella evolve within and over multiple infection cycles in wild and lab-reared rodents. Our lab is particularly interested in mechanisms for genome evolvability utilized by these bacteria to escape host immune responses, including simple-sequence repeat contingency loci, gene accordions, and recombination during co-infections.

Current Researchers: Isaac Gifford

Representative Publications

• Rodríguez‑Pastor et al. (2024) PLoS Pathogens PMID: 39348417
• Rodríguez‑Pastor et al. (2022) Molecular Ecology Resources PMID:35599628

Funding: BSF     Past Funding: NSF EEID