First draft

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INTRO/BACKGROUND

V. Chandrasekaran

Synthetic biology is defined as application of engineering and mathematical principles to create novel biological devices and novel biological circuits. This approach to biology has resulted in advances in medicinal chemistry (Martin et al., 2003, Tsuruta et al., 2009) and in genetic engineering (Hasty et. al., 2002, Sprinzak and Elowitz, 2005). In addition, advances in synthetic biology have led to creation of biological parts with the intention of assembling them into different combinations to create biological devices (Ferber et.al., 2004, Purnick and Weiss, 2009) and the creation of bacteria containing a synthesized genome (Gibson et al., 2010). In the last five years, the field of synthetic biology is emerging as an important area for interdisciplinary collaborations between STEM disciplines at the undergraduate level. Undergraduate student research has been an integral part of synthetic biology with the NSF sponsored undergraduate student research Jamboree in 2005 (Campbell, 2005) and the annual iGEM competition that attracts undergraduate student researchers from around the world to design biological devices that can address wide range of biological, environmental and mathematical problems. (http://2010.igem.org/Main_Page). The HHMI funded GCAT synthetic biology workshop organized by Dr. Malcolm Campbell at Davidson College was focused at teaching faculty, many of whom were from primarily undergraduate institutions, about synthetic biology and opportunities for incorporating synthetic biology in curriculum and undergraduate research as well as for forging interdisciplinary collaborations within their schools. This meeting report will highlight some of the important aspects of this workshop.

[Again, I tried tweaking, but it was stylistic and did not save any paper. RM]

MEETING THEMES

A number of themes appeared frequently throughout the workshop:

1. Synthetic biology requires a new way of thinking for most scientists: to view problems as an engineer would, considering issues of standardization, modularity, abstraction, and modeling and their applicability to the problem at hand.

2. Synthetic biology is an excellent pedagogical and research tool to foster interdisciplinary work and learning. Successful interdisciplinarity requires everyone to work at constantly communicating with your teammates — students and faculty in fields different than your own — and thinking about the problem in new ways.

3. Synthetic biology is incredibly flexible: almost any interest can be accommodated within the field, and this makes it relatively easy to find projects that require contributions from all members of the team. This is important, because if the biologist (or the mathematician, or the engineer, or the computer scientist, or ...) feels that their role in the overall project isn't important, it won't work. Nobody wants to play the fifth wheel.

4. This flexibility makes synthetic biology particularly accessible and stimulating for faculty at small schools and their undergraduate students: most of us are the only [fill in the blank] in our departments, so having a way to leverage the interests, knowledge, and excitement of colleagues we might not otherwise be able to collaborate with is a great situation to be in. Not only are we as faculty forced out of our intellectual comfort zones, but so are our students: exposing them to other approaches and ways of thinking as part of a hands-on research experience will give them an unparalleled appreciation of the value (and realities) of interdisciplinary thinking, something which will be increasingly valuable to them in the future.

[I'd like to replace "them" with "students" above in the statement so are our students: exposing them... TG]

5. The workshop leaders shared with us their goals for the projects they've undertaken:[bulleted list for these 3 items not wikiable, apparently] everyone (faculty and students) should learn new things everyone should have fun the project should contribute to the knowledge base in synthetic biology

As they told us more than once, those goals are in order: if you're learning and enjoying what you're doing, you're doing well. Oddly enough, focusing on their first two goals seems to have enabled them to consistently achieve the third as well.

["in order" meaning "hierarchic"...any other word a bit more clear...maybe just say goal 1 is the most important, followed by 2]

MEETING ACTIVITIES

Yixin Eric Yang

Workshop leaders and participants engaged in two and a half days of intensive discussion, presentations and hands-on wet lab experiences. The workshop started with interactive discussions on topics including the fundamental principles of synthetic biology, the suitability of synthetic biology for multidisciplinary research with undergraduate students, the connection and communication between biology and other collaborating disciplines, the elements that make a good project of synthetic biology, etc. The discussions were followed by an introduction to the Biobrick standard assembly scheme and the registry of standard biological parts maintained at Massachusetts Institute of Technology. Each participant pair worked to consolidate their learning by browsing biological parts and devices from registry to build a DNA construct allowing bacteria to fluoresce and float in response to the presence of arabinose. After the workshop leaders gave project examples revealing the real-world applications of synthetic biology in medicine, energy, environmental science and technology, the participant pairs explored the example projects exhibited on the International Genetically Engineered Machine (iGEM) competitions, and presented their favorite project to the group. In the evening, workshop leaders gave presentations showcasing the exciting outcomes of the undergraduate synthetic biology research collaborated by Davidson College and Western Missouri State University, including an iGEM gold-medal winning project. In the morning of the second day, the participants broke into biologist and non-biologist groups to have the “birds-of-a-feather” discussion. Overcoming the obstacles of identifying common interest, combining expertise from two different disciplines, and communicating using a shared language was the theme of this discussion. The discussion of ethical issues of synthetic biology was also on the agenda of the same morning. Bioethicists joined the lunch to address ethical concerns and answer questions. In the afternoon and evening, each participant pair collaborated by merging their interest and expertise and using what they learned from the workshop to develop a research project of synthetic biology with which they can engage undergraduate students. In the morning of the third day, all participant pairs gathered and presented their synthetic biology project ideas to the whole group. The workshop leaders and all participants were amazed by the creativity and diversity of the project ideas the interdisciplinary teams developed within a half day. The PowerPoint files of all the presentations were deposited on the GCAT website (http://www.bio.davidson.edu/projects/gcat/workshop_2010/workshop_2010_results.html) to share with interested colleagues. In addition to lectures and discussion, the workshop also put participants on wet-lab work each day to develop skills on basic techniques imperative to synthetic biology research including building a new biological part using PCR techniques and oligonucleotides assembly. By working together, pairs learned the potentials of each specialty and helped each other envision the project from a broader perspective. The workshop also created a community resource sharing mechanism including using GCAT-alog, a virtual freezer stock database of standard biological parts developed by Davidson College, “wikis” and online protocol sharing, to support each other in the synthetic biology research and teaching. As a parting gift, each participant pair received a collection of mini-registry of GCAT workshop - ten biological parts of promoters and reporter genes.

[I don't have any suggestions at the moment, but this section is where I'd try to condense first. Depending on how the journal counts things, and if we move the "Resources" section online, I think we're around 2100-2200 words at the moment, which isn't too much above their 2-page suggestion/limit ..CJ]


[Here is a possible condensation. I don't think I left anything out, just shortened descriptions. It saved about 100 words.RM] The workshop started with interactive discussions on topics including the fundamental principles of synthetic biology, the suitability of synthetic biology for multidisciplinary research with undergraduate students, the elements that make a good project of synthetic biology, etc. The discussions were followed by an introduction to the Biobrick standard assembly scheme and the registry of standard biological parts maintained at MIT. Each team worked to consolidate their learning by browsing biological parts and devices from registry to build a DNA construct allowing bacteria to fluoresce and float in response to the presence of arabinose. After the workshop leaders gave project examples of synthetic biology in medicine, energy, environmental science and technology, the teams explored the projects exhibited at the iGEM competitions, and presented their favorite project to the group. In the evening, workshop leaders gave presentations showcasing the exciting outcomes of the undergraduate synthetic biology research at Davidson College and Western Missouri State University, including an iGEM gold-medal winning project. In the morning of the second day, the participants broke into biologist and non-biologist groups to have the “birds-of-a-feather” discussion. Identifying areas of common interest, combining expertise from two different disciplines, and communicating using a shared language were the themes of this discussion. The discussion of ethical issues of synthetic biology was also on the agenda of the same morning. Bioethicists joined the lunch to address ethical concerns and answer questions. In the afternoon and evening, each team used their interests and expertise and what they learned from the workshop to develop a research project of synthetic biology with which they can engage undergraduates. In the morning of the third day, the teams gathered and presented their synthetic biology project ideas to the whole group. The workshop leaders and all participants were amazed by the creativity and diversity of the project ideas the interdisciplinary teams developed within a half day. The PowerPoint files of all the presentations were deposited on the GCAT website (http://www.bio.davidson.edu/projects/gcat/workshop_2010/workshop_2010_results.html) to share with interested colleagues. In addition to lectures and discussion, the workshop also put participants on wet-lab work each day to develop skills on basic techniques imperative to synthetic biology research including building a new biological part using PCR techniques and oligonucleotide assembly. By working together, pairs learned the potential of each specialty and helped each other envision the project from a broader perspective. The workshop also created community resource sharing mechanisms including using GCAT-alog, a virtual freezer stock database of standard biological parts developed by Davidson College, “wikis” and online protocol sharing, to support each other in the synthetic biology research and teaching. As a parting gift, each team received a GCAT mini-registry—ten biological parts of promoters and reporter genes.

FIGURE 1--Please see [1] [This grainy figure is 400kb and the actual one is 23Mb. I did not want to put the image in Wikimedia commons so I put it on my little website. Suggestions for brightness/contrast?] Figure 1. GCAT Synthetic Biology Workshop participants, organizers, and HHMI representatives. Top row (left to right): Laurie Heyer, Jeff Poet, Jeff Matocha, Nathan Reyna (back), Malcolm Campbell, Qiang Shi, Kathy Ogata; second row: Nighat P Kokan, Robert M. Jonas, Santiago Toledo, Vidya Chandrasekaran, Valerie Burke, Yixin Yang, Andrea Holgado, Anil L. Pereira; third row: Todd Eckdahl, Susmita Acharya, Consuelo Alvarez, Paul F. Hemler, Michael J. Wolyniak, Libby Shoop, Paul Overvoorde, Nathan Reyna, Matthew Tuthill, Carl Salter, Christopher Jones, Robert Morris, Tom Twardowski, Joyce Stamm, Talitha Washington; Last Row: all participants, Theresa Grana, Leo Lee, Jodi Schwarz, Teresa A. Garrett.

[I'd leave the question of brightness/contrast tweaks to the journal; they should know what works best for them ..CJ]

RESOURCES PROVIDED

(Andrea Holgado & Anil Pereira)

In order to facilitate the transition between ongoing research and synthetic biology multidisciplinary research, a number of resources were presented at the meeting.

1. GCAT Listserv: The GCAT Listserv (known as GCAT-L) is an email discussion list that connects faculty members who use (or are interested in using) genomic methods in their undergraduate courses. Messages sent to GCAT-L by any one of its subscribers are distributed to all of its other subscribers. Information on how to subscribe and use GCAT-L is posted at http://www.bio.davidson.edu/projects/gcat/GCAT-L.html

2. Wiggio/Wiki: Wiggio.com is an online toolkit that is freely available on the Internet. The toolkit is designed to make it easy to work in groups. It allows file sharing and editing, management of group calendars, posting of links, setting up conference calls, online chat, and sending text, voice and email messages to group members. Group members can define how they each want to be informed about group activity. The toolkit can be accessed at http://wiggio.com. The GCAT community Wiki has been setup for use by the GCAT community and is maintained by its users. The GCAT community Wiki can be accessed at http://gcat.davidson.edu/GcatWiki/index.php/Main_Page. The International Genetically Engineered Machine (iGEM) competition Wiki at http://2010.igem.org/Main_Page also contains a link to previous iGEM competitions. iGEM competitions are synthetic biology competitions for undergraduate students. Information on projects submitted by students to iGEM 2009 can be found at http://2009.igem.org/jamboree/Project_Abstract/Team_Abstracts.

3. Mini-Registry: A mini-registry was provided at the GCAT Synthetic Biology Workshop, 2010. The registry contains ten parts that are present in the Registry of Standard Biological Parts available at http://partsregistry.org/Main_Page. The parts include promoters, Ribosome Binding Sites (RBS), Double Terminators, Red Fluorescent Proteins (RFP) and Green Fluorescent Proteins (GFP).

4. Online Protocols: The various protocols used by GCAT members are described online at http://www.bio.davidson.edu/projects/gcat/GCATprotocols.html. This page contains a link to Brown lab’s protocol page, http://cmgm.stanford.edu/pbrown/mguide/index.html. Brown Lab is at Stanford University’s School of Medicine.

5. GCATalog: This catalog developed by Bill Hatfield, Laurie J. Heyer, and A. Malcolm Campbell at Davidson College is freely available and was optimized for synthetic biology. Using this web-based catalog, synthetic biology users can generate a freezer inventory and share commonly used BioBricks™ and more. http://gcat.davidson.edu/GCATalog/

6. Registry of Standard biological parts help page: A registry of standard parts to build synthetic biology devices is available at http://partsregistry.org/Main_Page. This dynamic collection was originated in 2003 at MIT with the purpose of simplifying the process of engineering biological devices. New users may also take advantage of the help-page; where detailed instructions related to BioBrick™ Standard Biological Parts repository, assembling and registering are explained.

7. Open WetWare: In order to promote sharing of unpublished work and protocols between scientists engaged in biological engineering, an open WetWare page was created http://openwetware.org/wiki/Main_Page. This page has information related to labs working in synthetic biology, course and teaching resources, protocols and a continually updated blog.

8. Synthetic Biology Tools: One of the highlighted website as repository of synthetic biology tools was Endy’s laboratory at Stanford University, Department of Bioengineering http://openwetware.org/wiki/Endy_Lab. This Open WetWare- linked laboratory website has information on ongoing research, publications and detailed descriptions of projects and tools generated.

[All of the protocols at the link in section 4 are for GCAT's other aspect (DNA microarrays) and don't appear to have anything to do with synthetic biology, so I'd delete it. Given the stringent length limitation, should this entire section ("Resources Provided") be moved to supplemental/online only version? And since these are all electronic or web-based, I'd just call it "Resources" and drop "Provided" myself ..CJ]

ASSESSMENT

M.J. Wolyniak

To gauge the effectiveness of the workshop in providing the resources and creative sparks necessary for developing synthetic biology projects in the classrooms and laboratories of its participants, thorough pre- and post-assessment surveys were conducted. The pre-assessment was administered online approximately one month before the gathering of participants at Davidson and the post-assessment was administered with pen and paper on the final day of the meeting. The questions on the two surveys compared the participants’ pre- and post- workshop perceptions of synthetic biology as a distinct field, as an area for multi-disciplinary collaboration, and as a viable option for their classroom and research programs. The results of the survey comparison revealed a general feeling of excitement and improved understanding about synthetic biology (Figure 2), with the vast majority agreeing with the comment from one participant who stated that “I now feel confident that I understand the basic ins and outs of synthetic biology—what it is and isn’t—as well as how I can implement projects in this area with my students.” Interestingly, although 75% of workshop attendees had basic previous experience in molecular biology laboratory work, data analysis, and experimental design, only 25% had ever engaged in a previous multidisciplinary collaboration. This trend was reflected in the post-assessment of the meeting as well, as many felt that the forging of collaborative projects that satisfy the intellectual curiosities of faculty from disparate disciplines stood as the most significant challenge towards the successful implementation of synthetic biology projects. Several participants noted that the meeting was, in the words of one attendee, “important to meet and establish a network of colleagues”, and it was evident to meeting participants that the establishment of collaborations between different disciplines and between different institutions of all sizes will contribute greatly towards the successful implementation of synthetic biology projects that expose students to the collaborative and multidisciplinary nature of modern scientific research. Indeed, the establishment of multidisciplinary collaborations engendered by this workshop is reflective of the need for academics of different disciplines to join forces to share ideas and resources in their educational endeavors as obstacles including scarcity of individual college resources and increased competition for research funding threatens to curtail the development of scientific educational opportunities for students (Dodson et al., 2010).


[I tried to squeeze this down a little, but could only find a dozen or so words to do without. RM] (Michael -would you like to insert Figure 2 at the end of paragraph 1 here? Theresa [2] Also, Figure 2 can be altered in any way you please. I combined biologists and non-biologists to keep the data simple since this is a short document. Non-biologists were less comfortable with all the questions, and especially questions D & E questions. I like what you wrote for assessment)

[I'd leave questions of layout/figure placement to the journal editors ..CJ]

FUTURE PLANS:RESEARCH Joyce Stamm and Talitha Washington

Research in synthetic biology is an excellent way to bridge the STEM disciplines in a way that is accessible to students. This research is well-suited for undergraduate involvement, as evidenced by the number of teams competing at iGEM (112 teams in 2009, 129 teams currently registered for 2010). While the majority of these teams are from research universities, primarily undergraduate institutions such as Davidson College and Missouri Western State University have been successful at the competition and have also published some of their work (Haynes et al., 2008, Jordan et al., 2009). Many undergraduate institutions are well-positioned to pursue projects in synthetic biology since only basic computer and molecular biology resources are needed, and the necessary reagents are relatively inexpensive. iGEM participation allows access to the entire library of available BioBricks; however, participation may be cost-prohibitive for many institutions. We are currently exploring strategies to address this issue but note that in the meantime, it is relatively simple to construct plasmids using BioBrick strategies.

There are a number of approaches that may be taken to develop research programs in synthetic biology, which range from student-generated, self-contained summer research projects to long-term, faculty-designed projects designed for student involvement over a number of years. To develop bona fide interdisciplinary projects, it is important to create the time and space for the idea generation. We suggest attending iGEM to see first-hand the myriad of approaches to synthetic biology. Communication by scheduling regular meetings between collaborating partners is essential for successful projects. The Davidson/Missouri Western team achieves this by holding weekly colloquia with interested students via a shared web-based communication system that connects the campuses. Over time, the professors and students gain an appreciation for the interconnectedness of different disciplines and most of all, they have fun.


FUTURE PLANS:COURSEWORK R. W. Morris CLASSROOM APPLICATIONS OF SYNTHETIC BIOLOGY

Brainstorming about ways to make a bacterial Lava lamp got most of us excited and thinking of the myriad things that bacteria know how to do. This could be a very good way to enlist the creative talents in one’s students. Whether or not it ever got built, contemplating the feasibility of such a project is very likely to elicit significant student buy-in.

Once the students have taken ownership of the overall picture, there are innumerable things to try, from straightforward to Byzantine. For example, one might ask if the dose response of an inducible promoter is linear by creating a promoter + ribosome binding site + GFP plasmid and measuring fluorescence as a function of inducer concentration. Cis-trans effects could be examined by using two plasmids, one carrying kanamycin resistance as well as one structure of interest and one with ampicillin resistance and the other structure. Other variables could include bacterial strain, ribosome binding site, distance between the various components, promoters, etc. Much new learning could occur with the available building blocks, or the students could create new ones to test their pet ideas. It seems to me that the only limitation is the imagination of the student. Any new creations would be entered into the catalog of parts available to the entire community.

The presentations we saw and the exercises we did sparked many conversations about ways to use this material in the class room. Accessibility of parts and willingness of those who know more to share with those of us who know less have most of us preparing lab experiences for the coming academic year and beyond.

[I think a SUMMARY section should be provided to focus on the questions that Malcolm and Erin Dolan provided us before we began:

SUMMARY Synthetic biology is a newly-emerging field, in which costs are relatively low and the value of student input can be high. It rewards tackling the sort of interdisciplinary problems that are increasingly important for our students' professional futures but are often difficult to undertake from our traditional disciplinary towers. Undergraduate students have shown both interest and ability in pursuing this research, as the results of 5 years of iGEM jamborees amply testify. [new paragraph] The organizers are considering the possibility of offering additional faculty workshops in future; if they do, we think that there cannot be a more focused, effective, and fun introduction to synthetic biology for those of you who want to explore this exciting new field. ..CJ]

WORKS CITED

Campbell M.A. (2005). Meeting Report: Synthetic Biology Jamboree for Undergraduates. Cell Biol Educ 4: 19-23.

Dodson MV, Guan LL, Fernyhough ME, Mir PS, Bucci L, McFarland DC, Novakofski J, Reecy JM, Ajuwon KM, Thompson DP, Hausman GJ, Benson M, Bergen WG, Jiang Z. (2010). Perspectives on the formation of an interdisciplinary research team. Biochem Biophys Res Commun. 391(2): 1155-7.

Ferber, D. (2004). Microbes made to order. Science 303, 158 -161.

Gibson D.G., Glass J.I., Lartigue C., Noskov V.N., Chuang R., Algire M. A., Benders G.A., Montague M.G., Ma L., Moodie M.M., Merryman C., Vashee S., Krishnakumar R., Assad-Garcia N., Andrews-Pfannkoch C., Denisova E.A., Young L., Qi Z., Segall-Shapiro T.H., Calvey C.H., Parmar P.P., Hutchison III C.A., Smith H.O., and Venter J.C. (2010) Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science 329 (5987), 52. [DOI: 10.1126/science.1190719]

Hasty, J., McMillen, D., and Collins, J.J. (2002). Engineered gene circuits. Nature 240, 224 -230.

Haynes KA, Broderick ML, Brown AD, Butner TL , Dickson JO, Harden WL, Heard LH, Jessen EL, Malloy KJ, Ogden BJ, Rosemond S, Simpson S, Zwack E, Campbell AM, Eckdahl TT, Heyer LJ, Poet JL (2008 ). Engineering bacteria to solve the Burnt Pancake Problem. J. Biol. Eng 2: 1-12.

Jordan B, Acker K, Adefuye O, Crowley ST, DeLoache W, Dickson JO, Heard L, Martens AT, Morton N, Ritter M, Shoecraft A, Treece J, Unzicker M, Valencia A, Waters M, Campbell AM, Heyer LJ, Jeffrey L. Poet JL Todd T. Eckdahl TT. (2009). Solving a Hamiltonian Path Problem with a Bacterial Computer. J. Biol. Eng. 3:11

Martin V.J., Pitera D.J., Withers S.T., Newman J.D. and Keasling J.D. (2003). Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotechnol 21,796–802

Purnick P.E.M. and Weiss R. (2009). The second wave of synthetic biology: from modules to systems. Nat. Rev. Mol. Cell Biol. 10, 410-422

Sprinzak D., and Elowitz M.B. (2009). Reconstruction of genetic circuits. Nature 438, 443-448.

Tsuruta H., Paddon C.J., Eng D., Lenihan J.R., Horning T., Anthony L.C., Regentin R., Keasling J.D., Renninger N.S., and Newman J.D. (2009). High-Level Production of Amorpha-4,11-Diene, a Precursor of the Antimalarial Agent Artemisinin, in Escherichia coli. PLoS ONE 4(2): e4489.

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