Barrick Lab :: Research

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---+!! Barrick Lab :: Research

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#EngineeringInsectSymbionts
---++ Engineering Insect Symbionts

Many insects have more consequential associations with bacteria than we have with the human microbiome. Recently, we have begun to genetically engineer these bacteria to study these symbioses and to affect their insect hosts. These projects are highly collaborative and have also involved researchers from the [[http://web.biosci.utexas.edu/moran/][Moran Lab]], the [[https://ellingtonlab.org/][Ellington Lab]], and other labs.

*Funding:* DARPA BRICS, DARPA Insect Allies, ARO MURI

---+++ Honey Bees: Protecting Pollinator Health
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<center><img src="%ATTACHURLPATH%/Leonard_2020_Science.png" width='400' /> %BR%
*Engineered symbionts kill bee parasites* </center>
</div>Bees are ecologically and economically important pollinators. We created a bee microbiome toolkit (BTK) for engineering bacteria that colonize the guts of honey bees (_Apis mellifera_) and bumble bees (_Bombus species_). We showed that we can engineer the bacterium _Snodgrassella alvi_ to implement effective symbiont-mediated RNAi. This system can be used for the targeted knockdown of bee genes to study their functions. For example, we have used it to alter honey bee feeding behavior. We have also shown that these engineered symbionts can be used to protect honey bees from viral pathogens and arthropod parasites that imperil the health of hives.

*Researchers:* [[LabPersonnel#SLeonard][Sean Leonard]], [[LabPersonnel#PengGeng][Peng Geng]]

*Representative Publications*
   * Leonard et al. (2020) _Science_  [[https://www.ncbi.nlm.nih.gov/pubmed/32001655][PMID: 32001655]]
   * Leonard et al. (2018) _ACS Synthetic Biol._ [[https://www.ncbi.nlm.nih.gov/pubmed/29608282][PMID: 29608282]]
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---+++ Aphids: Understanding the Evolution of an Endosymbiont
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<center><img src="%ATTACHURLPATH%/website_fig_aphid.png" alt="website_fig_aphid.png" width='400'  /> %BR% *GFP-tagged symbiont colonizes the aphid gut* </center>
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Aphids are plant pests and model systems for studying symbioses. We have developed tools for engineering strains of _Serratia symbiotica_ that colonize the aphid gut. We are now using these tools to unravel how these strains, which can be pathogenic to their hosts, are related to strains of _S. symbiotica_ that live within insect cells, are inherited across aphid generations, and can benefit their aphid hosts. We have showed that cultured _S. symbiotica_ strains are capable of maternal transmission within aphids, suggesting that they possess a latent capacity to evolve a long-term symbiotic relationship with their hosts. We are also exploring applications of these engineered bacteria related to pest control.

*Researchers:* [[LabPersonnel#KElston][Kate Elston]], [[LabPersonnel#JPerreau][Julie Perreau]]

*Representative Publications*
   * Elston et al. (2020) _Appl. Env. Microbiol._ [[https://www.biorxiv.org/content/10.1101/2020.09.15.299214v1][bioRxiv]]
   * Perreau et al (2020) _Submitted_ [[https://www.biorxiv.org/content/10.1101/2020.09.01.279018v1][bioRxiv]]
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---+++ Leafhoppers: Studying and Engineering Natural Nanomaterials
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 <center><img src="%ATTACHURLPATH%/leafhopper_website.png" alt="leafhopper_website.png" width='400' />%BR%* Leafhopper and SEM image of brochosomes on its wing* </center>
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Leafhoppers produce unique nanostructures, called brochosomes, that they anoint onto their wings and sometimes eggs. Brochosomes have interesting materials properties, including superhydrophobicity and omnidirectional antireflectivity. We are characterizing natural variation in brochosome structure and performing comparative genomics to understand the molecular components that make up these structures and how they evolved. We are also working towards genetically engineering symbionts of leafhoppers to create new tools for studying brochosomes and potentially enhancing their properties.
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*Researchers:*  [[LabPersonnel#SBialik][Sarah Bialik]], [[LabPersonnel#KElston][Kate Elston]], [[LabPersonnel#PengGeng][Peng Geng]], [[LabPersonnel#ERobinson][Elizabeth Robinson]]
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#PreventingEvolutionaryFailure
---++ Preventing Evolutionary Failure in Synthetic Biology

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*Evolutionary half-lives of biological devices* </center>
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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. This work includes:  (1) the development of the Evolutionary Failure Mode (EFM) Calculator software for identifying mutational hotspots in a designed DNA sequence; (2) using experimental evolution to identify "antimutator" variants of host organisms that lead to lower-than-natural mutation rates; and (3) designing genetic circuits that kill those cells within a population that are most likely to accumulate mutations.

*Resources*
   * [[http://barricklab.org/efm][Evolutionary Failure Mode (EFM) Calculator website]]

*Representative Publications*
   * Jack et al. (2015) _ACS Synthetic Biol._ [[http://www.ncbi.nlm.nih.gov/pubmed/26096262][PMID:26096262]]
   * Renda et al. (2014) _Mol. Biosyst._  [[http://www.ncbi.nlm.nih.gov/pubmed/24556867][PMID:24556867]]

*Funding:* DARPA BRICS

#GenomeDynamics
---++ Dynamics of Microbial Genome Evolution

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*Accumulation of mutations in population Ara-1 of the LTEE over 20,000 generations of evolution* </center>
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We develop the [[http://barricklab.org/breseq][<i>breseq</i>]] 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 30-year Lenski [[http://myxo.css.msu.edu/ecoli/][long-term evolution experiment (LTEE) ]] with _E. coli_. We continue to develop _breseq_ 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 (such as oncoviruses) can anticipate further evolutionary trajectories and how this information might be used to better diagnose disease outcomes. 

*Resources*
   * [[http://barricklab.org/breseq][<i>breseq</i> project page]]
   * [[https://github.com/barricklab/breseq][<i>breseq</i> code and downloads (GitHub)]]
   * [[https://github.com/barricklab/LTEE-Ecoli][LTEE genome resources (GitHub)]]
*Representative Publications*
   * Deatherage et al. (2017) _Proc. Natl. Acad. Sci._ [[https://www.ncbi.nlm.nih.gov/pubmed/28202733][PMID: 28202733]]
   * Tenaillon et al. (2016) _Nature_ [[https://www.ncbi.nlm.nih.gov/pubmed/27479321][PMID: 27479321]]
   * Deatherage and Barrick (2014) _Methods Mol. Biol_ [[http://www.ncbi.nlm.nih.gov/pubmed/24838886][PMID:24838886]]
   * Barrick and Lenski (2014) _Nat. Rev. Genet._ [[http://www.ncbi.nlm.nih.gov/pubmed/24166031][PMID:24166031]]

*Funding:* NIH K99/R00, NSF, NSF BEACON Center, CPRIT

---++ Evolution and Engineering of Naturally Transformable Bacteria 

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*Insertion sequences (red) deleted in the transposon-free strain _Acinetobacter baylyi_ ADP1-ISx* </center>
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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.

<p />
<strong>Personnel</strong> <ul>
<li> <a href="https://barricklab.org/twiki/bin/view/Lab/LabPersonnel#IGifford">Isaac Gifford</a>
</li></ul> 
<p />

*Representative Publications*
   * Suárez et al. (2020) _Nucleic Acids Res._ [[https://academic.oup.com/nar/article/48/8/4585/5813807][PMID:32232367]] 
   * Suárez et al. (2017) _Appl. Env. Microbiol._ [[http://www.ncbi.nlm.nih.gov/pubmed/28667117][PMID:28667117]] 
   * Renda et al. (2015) _J. Bacteriol._ [[http://www.ncbi.nlm.nih.gov/pubmed/25512307][PMID:25512307]] 

*Funding:* Welch Foundation

---++Evolution and Engineering of Bacteriophages<a name="Evolution and Engineering of Bacteriophages"></a>
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<center><img src="%ATTACHURLPATH%/Pinetree_Phage_Glyph.png" width='280' /> <br />
<figcaption><b>Glyphs representing <a href="https://doi.org/10.1093/bioinformatics/btz203" target="_top">Pinetree</a> being used to examine phage genome architecture.</b></figcaption>
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<p />
The rise of multiple drug resistant pathogenic bacteria has raised the question of available, robust alternatives to antibiotics for disease treatment. Our lab is exploring new techniques for modifying bacteriophages for use in phage therapy. Evolution, engineering, and expansion of bacteriophage genomes has the potential to diversify target diseases for treatment, perform diagnostics for proactive disease prevention, and improve the efficacy of existing applications. We are working to accomplish these advancements through computational simulations and non-standard amino acid integration. The introduction of non-standard amino acids into the repertoire of protein production also brings insights into evolutionary outcomes that may not be possible in existing natural environments. Learning about evolution enabled by non-standard amino acids can lead to applications beyond the scope of viruses.
<p />
<strong>Personnel</strong> <ul>
<li> <a href="https://barricklab.org/twiki/bin/view/Lab/LabPersonnel#Peng Geng">Peng Geng</a>
<li> <a href="https://barricklab.org/twiki/bin/view/Lab/LabPersonnel#CRoots">Cameron Roots</a>
<li> <a href="https://barricklab.org/twiki/bin/view/Lab/UTiGEMTeam">UT Austin iGEM</a>
<li> In collaboration with the <a href="https://wilkelab.org/">Wilke Lab</a>
</li></ul> 
<p />
<strong>Representative Publication</strong> <ul>
<li> Hammerling et al. (2014) <em>Nature Chemical Biology.</em> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24487692/" target="_top">PMID:24487692</a>
</li></ul> 
<p />
<strong>Funding:</strong> NIH R01
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[[PreviousResearch][Previous Research Projects]]

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This topic: Lab > WebHome > ResearchInterests
Topic revision: r48 - 2020-12-03 - JeffreyBarrick