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Burrill, Devin Rene

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Burrill

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Devin Rene

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Burrill, Devin Rene
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    Portable, On-Demand Biomolecular Manufacturing
    (Elsevier BV, 2016) Pardee, Keith; Slomovic, Shimyn; Nguyen, Peter; Lee, Jeong Wook; Donghia, Nina; Burrill, Devin Rene; Ferrante, Tom; McSorley, Fern R.; Furuta, Yoshikazu; Vernet, Andyna; Lewandowski, Michael; Boddy, Christopher N.; Joshi, Neel; Collins, James
    Synthetic biology uses living cells as molecular foundries for the biosynthesis of drugs, therapeutic proteins, and other commodities. However, the need for specialized equipment and refrigeration for production and distribution poses a challenge for the delivery of these technologies to the field and to low-resource areas. Here, we present a portable plat- form that provides the means for on-site, on-demand manufacturing of therapeutics and biomolecules. This flexible system is based on reaction pellets composed of freeze-dried, cell-free transcription and translation machinery, which can be easily hy- drated and utilized for biosynthesis through the addition of DNA encoding the desired output. We demonstrate this approach with the manufacture and functional validation of antimicrobial peptides and vaccines and present combinatorial methods for the production of antibody conjugates and small molecules. This synthetic biology platform resolves important practical limitations in the production and distribution of therapeutics and molecular tools, both to the developed and developing world.
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    A BioBrick compatible strategy for genetic modification of plants
    (BioMed Central, 2012) Boyle, Patrick M; Burrill, Devin Rene; Inniss, Mara Christine; Agapakis, Christina M; Deardon, Aaron; dewerd, Jonathan; Gedeon, Michael A; Quinn, Jacqueline Y; Paull, Morgan L; Raman, Anugraha M; Theilmann, Mark R; Wang, Lu; Winn, Julia C; Medvedik, Oliver; Schellenberg, Kurt William; Haynes, Karmella A.; Viel, Alain; Brenner, Tamara; Church, George; Shah, Jagesh; Silver, Pamela
    Background: Plant biotechnology can be leveraged to produce food, fuel, medicine, and materials. Standardized methods advocated by the synthetic biology community can accelerate the plant design cycle, ultimately making plant engineering more widely accessible to bioengineers who can contribute diverse creative input to the design process. Results: This paper presents work done largely by undergraduate students participating in the 2010 International Genetically Engineered Machines (iGEM) competition. Described here is a framework for engineering the model plant Arabidopsis thaliana with standardized, BioBrick compatible vectors and parts available through the Registry of Standard Biological Parts (http://www.partsregistry.org). This system was used to engineer a proof-of-concept plant that exogenously expresses the taste-inverting protein miraculin. Conclusions: Our work is intended to encourage future iGEM teams and other synthetic biologists to use plants as a genetic chassis. Our workflow simplifies the use of standardized parts in plant systems, allowing the construction and expression of heterologous genes in plants within the timeframe allotted for typical iGEM projects.
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    Publication
    Tracking Cell Fate with Synthetic Memory Circuits
    (2013-03-18) Burrill, Devin Rene; Silver, Pamela A.; Winston, Fred Marshall; Lahav, Galit; Voigt, Christopher; Weiss, Ron
    The capacity of cells to sense transient environmental cues and activate prolonged cellular responses is a recurring biological feature relevant to disease development and stem cell differentiation. While biologically significant, heterogeneity in sustained responses is frequently masked by population-level measurements, preventing exploration of cellular subsets. This thesis describes the development of tools for tracking the fate of subpopulations that differentially respond to DNA damage or hypoxia, illuminating how heterogeneous responses to these inputs affect long- term cell behavior and susceptibility to future dysfunction or disease. Taking a synthetic biology approach, I engineered genetic positive feedback loops that employ bistable, auto-regulatory transcription to retain memory of exposure to a stimulus. Strongly responsive cells activate these memory devices, while more weakly responsive cells do not, enabling the tracking and characterization of two subpopulations. Chapters 2 and 4 detail a yeast memory device used to track cells that differentially activate repair pathways after DNA damage. Chapter 3 describes a mammalian memory system used to follow subpopulations that uniquely respond to DNA damage or hypoxia. Both the yeast and mammalian systems capture subpopulations that differ in biological behavior for multiple generations, indicating a transmissible memory of the environmental perturbations that contributes toward distinct cell fates. Collectively, this work advances our understanding of the relationship between heterogeneous cell behavior and cellular memory in the context of disease development.