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             <div>Public Engagement</div>
 
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           <div class="sectionTitle" id="Section 1">Section 1</div>
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           <div class="sectionTitle" id="Section 1">Mick and Mates Podcast</div>
 
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                 The lack of a versatile and reliable way to improve metabolic flux channeling, pathway orthogonality, and product yields is a major impediment to the expanded utilization of biosynthesis for the production of drugs and industrially valuable chemicals. Manifold, a platform technology that addresses this problem, consists of <div class="dict">bacterial microcompartments<span><img src="https://upload.wikimedia.org/wikipedia/commons/thumb/2/25/Carboxysome_and_bacterial_microcompartments.jpg/800px-Carboxysome_and_bacterial_microcompartments.jpg"/>Bacterial microcompartments (BMCs) are organelle-like structures, consisting of a protein shell that encloses enzymes and other proteins. BMCs are typically about 40–200 nanometers in diameter and are entirely made of proteins. The shell functions like a membrane, as it is selectively permeable.</span></div> (BMCs) with encapsulated dsDNA scaffolds <div class="ref">[1]<span>Elbaz, J., Yin, P., &amp; Voigt, C. A. (2016). Genetic encoding of DNA nanostructures and their self-assembly in living bacteria. Nature communications, 7(1), 1-11.</span></div> that sequester and spatially organize, at fixed concentrations, biosynthetic enzymes presented as zinc-finger fusion proteins. Here we deliver the designs for an E. coli cell capable of synthesizing resveratrol using the Manifold platform. The Manifold platform will help lower costs and expand the applications of chemical biosynthesis. The lack of a versatile and reliable way to improve metabolic flux channeling, pathway orthogonality, and product yields is a major impediment to the expanded utilization of biosynthesis for the production of drugs and industrially valuable chemicals. Manifold, a platform technology that addresses this problem, consists of bacterial microcompartments (BMCs) with encapsulated dsDNA scaffolds that sequester and spatially organize, at fixed concentrations, biosynthetic enzymes presented as zinc-finger fusion proteins. Here we deliver the designs for an E. coli cell capable of synthesizing resveratrol using the Manifold platform. The Manifold platform will help lower costs and expand the applications of chemical biosynthesis.
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                 In an effort to broaden the horizons of the general public in regards to Synthetic Biology, team member Eddie Micklovic began a podcast, meant to elaborate on the work being done in the synthetic biology field, the opposing viewpoints that arise from that work, and how we all can stay informed. In the inaugural episode of the podcast, Eddie interviews Hank Greely, professor of law and director of  the Stanford Center for Law and the Biosciences, breaking down some of the legal and political ramifications that Synthetic Biology has posed. In his second episode, Eddie talks to UVA student Jacob Anish to discuss and explain Synthetic Biology from a surface-level perspective. These episodes are informative and enjoyable, and helped us to develop how we speak about the field itself. We hope you enjoy them as well. <br/>
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           <div class="sectionTitle" id="Section 2">Section 2</div>
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           <div class="sectionTitle" id="Section 2">Code of Ethical Conduct</div>
 
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               The invention consists of a protein shell comprising one or more proteins, one or more nucleic acid scaffolds of which there can be multiple copies, anabolic and/or catabolic enzymes specific to the desired biosynthesis pathway each containing a nucleic acid binding domain, recognition sequences for the utilized nucleic acid binding domains, nucleic acid spacers, and a linkage between the nucleic acid scaffolds and the protein shell. The protein shell (10) can take the form of any closed or open surface that comprises one or more repeating protein units (12). Examples of valid shells include bacterial microcompartments such as the Pdu, Eut, and carboxysome microcompartments, as well as modified,  but not necessarily closed, surfaces composed of mutated versions of these microcompartment shell proteins. The nucleic acid scaffolds (18) comprise multiple recognition sequences (22) and spacers (32) and can be made from any form of nucleic acid, including: deoxyribonucleic acid, ribonucleic acid, and synthetic nucleic acids such as xeno nucleic acids and peptide nucleic acids among others. These scaffolds are attached to the protein shell. The pathway enzymes are biological proteins whose exact sequences are dependent on the given use case of the invention, but which all contain a nucleic acid binding domain either internal to their structure, or at their N or C terminus.  
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               Over the course of the summer, our team turned our focus internally in order to grapple with the current state of our country and the obligation and responsibility we have as scientists. As it turns out, our team has tons of diverse perspectives, and many of the routes we considered for HP research arose from these differing opinions.  
 
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               Protests in late May, and the #ShutDownStem day initially inspired internal discussions about the role of scientists in social movements. We established formal, seminar-style discussions about how we as a team could respond and help to be part of the solution, and out of these discussions came an obvious need for a set of agreed team values. As a result, we sought to solidify our understanding through the writing of our own Code of Ethical Conduct. This document is a collection of our team’s stances and represents our dedication to standing by these principles. In this document, we outline our statement of values, specific laws, Diversity &amp; Inclusion Rules, Safety and Security, and Implementation. We created this as a code applicable to all iGem teams, taking into account differing global perspectives and ideals in the everchanging bioethical landscape. We’ve checked this document through UVA faculty, including bioethicists and biology professors, and after a final review of our team members, it was ratified. Now we present it to all future iGEM teams to edit, debate, and implement as well. We hope you can take the framework this document provides and determine your own team values, all in the pursuit of being better, more conscious, scientists.  
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              <b>Fig 1.</b> Figure taken from iGEM Tainan 2019 for demo purposes. Notice how the figure is much longer than it is wide, and two images are coupled together to achive this. Try to do that as well so it looks good.
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               Additionally, protein linkers are usually present between this nucleic acid binding domain and the enzyme structure to prevent inhibition of enzyme activity. However the exact linker(s) used,  if any, is(are) also dependent on the specific use case of the invention. These pathway enzymes are attached to the nucleic acid scaffolds via their nucleic acid binding domains. The nucleic acid recognition sequences (22) are unique or semi-unique sequences of nucleic acid monomers on the nucleic acid scaffolds to which the utilized nucleic acid binding domains have some degree of molecular complementarity. These nucleic recognition sequences comprise most of the scaffold and mark the locations to which the DNA binding domains of the pathway enzymes attach to the scaffolds. The nucleic acid spacers (32) are relatively short sequences of nucleic acid monomers that are also present on the nucleic acid scaffolds, between the recognition sequences. The linkage between the nucleic acid scaffolds (18) and protein shell (10) provides a means by which the nucleic acid scaffolds are bound to the protein shell through direct or multi-molecule complementarity. This linkage is found between the nucleic acid scaffolds and the protein shell. One example is through the addition of a nucleic acid binding domain (24) to one or more of the shell proteins forming a nucleic acid binding domain, shell protein fusion (14). Like the pathway enzymes, this nucleic acid binding-domain can be either internal to the shell protein structure or at its N or C terminus, where the exact placement depends on the shell protein being utilized. Alternatively, one or more intermediate proteins can be used to adhere the nucleic acid scaffolds to the shell, where the region of the protein interacting with the shell binds the shell via protein-protein complementarity (28) with a given shell protein, and the region of the protein interacting with the nucleic acid scaffold binds another recognition sequence on the nucleic acid scaffold through another nucleic acid binding domain (30). This forms a shell protein binding, nucleic acid domain fusion (26).<br/><br/><br/>
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Revision as of 20:37, 24 October 2020

Manifold

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Public Engagement
Mick and Mates Podcast
In an effort to broaden the horizons of the general public in regards to Synthetic Biology, team member Eddie Micklovic began a podcast, meant to elaborate on the work being done in the synthetic biology field, the opposing viewpoints that arise from that work, and how we all can stay informed. In the inaugural episode of the podcast, Eddie interviews Hank Greely, professor of law and director of the Stanford Center for Law and the Biosciences, breaking down some of the legal and political ramifications that Synthetic Biology has posed. In his second episode, Eddie talks to UVA student Jacob Anish to discuss and explain Synthetic Biology from a surface-level perspective. These episodes are informative and enjoyable, and helped us to develop how we speak about the field itself. We hope you enjoy them as well.

Code of Ethical Conduct
Over the course of the summer, our team turned our focus internally in order to grapple with the current state of our country and the obligation and responsibility we have as scientists. As it turns out, our team has tons of diverse perspectives, and many of the routes we considered for HP research arose from these differing opinions.
Protests in late May, and the #ShutDownStem day initially inspired internal discussions about the role of scientists in social movements. We established formal, seminar-style discussions about how we as a team could respond and help to be part of the solution, and out of these discussions came an obvious need for a set of agreed team values. As a result, we sought to solidify our understanding through the writing of our own Code of Ethical Conduct. This document is a collection of our team’s stances and represents our dedication to standing by these principles. In this document, we outline our statement of values, specific laws, Diversity & Inclusion Rules, Safety and Security, and Implementation. We created this as a code applicable to all iGem teams, taking into account differing global perspectives and ideals in the everchanging bioethical landscape. We’ve checked this document through UVA faculty, including bioethicists and biology professors, and after a final review of our team members, it was ratified. Now we present it to all future iGEM teams to edit, debate, and implement as well. We hope you can take the framework this document provides and determine your own team values, all in the pursuit of being better, more conscious, scientists.





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