(r39) Barrick Lab :: Research

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#PreventingEvolutionaryFailure
---++ Engineering Insect Symbionts

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*BTK* </center>
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We explore engineering endosymbionts in insects, including bees, aphids, and leafhoppers. We have created the bee microbiome toolkit (BTK) that can be used to engineer bacteria found in various insects and their gut microbiomes, as demonstrated in honey bees (_Apis mellifera_) and bumble bees (_Bombus_ species). Specifically, we have engineered an induced RNAi response in a native gut bacterium, _Snodgrassella alvi_. Colony collapse in bees is often contributed to two factors: _Varroa_ mites and deformed wing virus. Engineered _S. alvi_ has been shown to kill the mites and improve bee health. This symbiont-mediated approach is helpful to protect insects that are beneficial to human health, but can this approach can also be applied to pest species to improve food security. 

In aphids, we are engineering the endosymbiont _Serratia symbiotica_ to improve protection of food crops. Aphids are known to be agricultural pests, but by engineering native bacteria, such as _S. symbtiotica_, we can create a natural pest control option that is insect-specific, compared to insecticides that kill both beneficial and pest insects. We are also exploring another way to use engineered symbionts in another pest insect: leafhoppers. Leafhoppers produce unique nanostructures, called brochosomes, that are super hydrophobic and have novel optical properties. Instead of changing them to be less harmful to our food crops, we want to engineer their symbionts to use them to benefit humans. We hope to create a similar toolkit as the BTK for brochosomes via proteomics to create a new way of synthesizing useful biomaterials.


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*Decreased survival shown in mites* </center>
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*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]]

*Funding:* DARPA BRICS, DARPA AEPHID, MURI ARO


#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

---++ Evolving and Engineering Naturally Transformable Bacteria

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Naturally competent bacteria may have increased evolutionary potential because they can directly acquire new genes from their environments and incorporate them into their genomes. In addition to this possibility of a new mutational move in genotype-phenotype space (by horizontal gene transfer), these microbes provide an improved platform for studying microbial genome engineering and evolution due to the ease of reconstructing mutations and introducing new genes. We are investigating sources of genetic instability in the naturally competent bacterium _Acinetobacter baylyi_ ADP1 and engineering a clean genome version of this strain to have reduced rates of mutations that lead to inactivation of introduced genes for synthetic biology applications. We are also using experimental evolution to test for the utility of providing foreign DNA sequences and to understand how horizontally acquired genes become domesticated after they are incorporated into a new genome. Finally, we are using ADP1 as a platform for understanding the limits of simplifying a bacterial genome by evolutionary streamlining approaches.

*Representative Publication*
   * Suárez et al. (2020) _Nucleic Acids Res._ [[https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa204/5813807][preprint]] 
   * 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

[[PreviousResearch][Previous Research Projects]]

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Barrick Lab > ResearchInterests
Contributors to this topic
JeffreyBarrick, KateElston, SarahBialik, IsaacGifford, AlexaMorton, CameronRoots, GabrielSuarez, JuliePerreau
Topic revision: r39 - 2020-07-30 - 19:33:02 - Main.JeffreyBarrick