Gil Alterowitz: Each of the talks represented a different piece in the workflow. In this session, we want to see how they will eventually fit together. - Ruchira S. Datta

Questions 1: a) In this field, how can investigators from different fields work together and interact given: different terminologies, standards, knowledge bases in different disciplines? An arrow can have many different meanings, and many different symbols may have the same meanings. b) How should we deal with new ethical considerations that arise in the field of synthetic biology? - Ruchira S. Datta

Chitta Baral: We do need to work with different domain logics and knowledge bases. Have been working on data integration approach to try to marry them, but this is definitely a challenge. Some sort of collaborative platform, such as a wiki, may help. - Ruchira S. Datta

Ed Marcotte: How is this different for synthetic biology than the rest of biology? - Ruchira S. Datta

Gil Alterowitz: Was going to look first at the bioinformatics side, then look at the parts registry. When you think about doing it for the purposes of design, sometimes you do think about things differently. - Ruchira S. Datta

Larry Hunter: There's also the field of engineering. The instruments builders are closer to this world. - Ruchira S. Datta

Gil Alterowitz: Eric Davidson, please discuss parts registry, as well as open wetware and other open source projects. - Ruchira S. Datta

Eric Davidson: More familiar with MIT registry of standardized parts, for education and iGEM. They're only standardized to a certain extent. Even between different strains of E. coli, there can be dramatic differences. - Ruchira S. Datta

Ed Marcotte: Some of those differences can be extreme to the point of inverting the operation of a part. - Ruchira S. Datta

Eric Davidson: Parts are thought of as circuit designs, but need to consider they are operating within a host organism. Design in terms of the chassis. - Ruchira S. Datta

Gil Alterowitz: Re Q1b. A few years back, the sequence of the poliovirus was released, causing quite a scare. What if extinct kinds of bacteria or viruses that we thought were eradicated were synthesized and released, or studied as a biological agent by a foreign government? Also, know personally of an article that was in the review process for a very long time, because it was thought to be a cookbook for how to make a dangerous organism (thinks, anthrax). The article had to be watered down. This was a few years ago. People think about these when deciding which experiments to even design in the first place. Quote from the tutorial: someone asked J. Craig Venter, "Are you playing God now?" He answered, "We're not playing." - Ruchira S. Datta

Matt Lux: Have a little experience due to contacts with various defense-related entities. Interest in synthetic biology has been growing in the community, both in terms of sensors and in terms of engineered viruses and engineered threats. People are interested in what kinds of threats may be posed and what can be done about it. There are a lot of people working on it in government and elsewhere. - Ruchira S. Datta

Q Re Q1a: What does the community currently do to share terminologies, knowledge bases, and so forth? - Ruchira S. Datta

Chitta Baral: In some domains, have normalization to unique identifiers. - Ruchira S. Datta

Q: There is the Shared Names Database, and also the National Center for Biomedical Ontology to get public identifiers for, e.g., parts of the cell, in order to reuse. - Ruchira S. Datta

Gil Alterowitz: NCBO is a leader in integrating knowledge sources and has grown a lot even within the last year. - Ruchira S. Datta

Q: Q1a is a great question for interdisciplinary fields. At UT Austin, had 15 faculty members studying prostate cancer treatments and controls, as well as people from industry. Had weekly meetings for people to talk, each with their own terminologies. People need to be willing to step outside their own comfort zones. Human interaction is very important to making all those terminologies converge. This project was successful as everyone was willing to communicate. In this project, an anthropologist was studying us and how we communicate. - Ruchira S. Datta

Questions 2: a) How can we integrate knowledge from other areas (e.g., other session topics like dynamic networks, personal genomics, etc.)? b) Discuss OpenWetWare, related open source projects-what role should they play? c) What role can informatics play in the future of synthetic biology? d) How can industry/academia relationships be facilitated in this area? - Ruchira S. Datta

Chitta Baral: Invited talks relating to multiple sessions would be useful. My work was related to the dynamic networks, some of these things were discussed by Mona in her tutorial. - Ruchira S. Datta

Archana Ramesh: The main focus of my work has involved context-specific gene regulatory networks, where the context involves the phenotypic conditions in which they exist. Most databases, ontologies, or knowledge bases lack that information. Thus, many methods tend to ignore this information, which would be useful, e.g., for personalized medicine. In terms of curation and putting that information together, we informaticians have a role to play. - Ruchira S. Datta

May Wang: When co-chairing the session, intended to divert some papers to other sessions. Analogy with relationship between computer graphics and computer vision, or speech analysis and speech synthesis. Thus, synthetic biology is related to, but different from, many existing fields. Speakers, why did you submit to this session instead of others? - Ruchira S. Datta

Chitta Baral: Thought of the dynamic networks session, didn't know quite what the dynamic part meant, but after hearing the tutorial, it could have gone in there too. - Ruchira S. Datta

Matt Lux: There is room for those two approaches to come together more. Synthetic biologists think of putting together simple circuits and oscillators, but a lot of these already exist in nature. Maybe you can find what you want in existence in some organism, rather than doing it from scratch. - Ruchira S. Datta

Gianna Maria Toffolo: From modeling point of view, synthetic biology has most in common with dynamic networks, but the scale is different. In networks have many genes and interactions, and the topology is not completely known. In synthetic biology, the circuits are simpler. Can apply available engineering techniques such as parameter identification, studying oscillations, steady states, bifurcations, because there are only a few parameters. Another important thing is the deterministic approach and the stochastic approach. - Ruchira S. Datta

Ed Marcotte: At what network scale do these approaches break down? - Ruchira S. Datta

Gianna Maria Toffolo: To apply stochastic analysis, you need to know the model, so up to now this has been applied to simple circuits of which you have a lot of knowledge. Very hard to apply if don't know the topology or properties. Have worked only with an order of magnitude of ten. - Ruchira S. Datta

Gil Alterowitz: It sounds as though if you applied machine learning, you could learn the probabilities. - Ruchira S. Datta

Matt Lux: Tyson's cell cycle model has a hundred parameters. They have done a reduced model stochastically, but have not been able to do the full model. Don't know all the parameters with great confidence. - Ruchira S. Datta

Gil Alterowitz: Q2b. Drew Endy started OpenWetWare, then moved to Stanford, but it still works. What about code? - Ruchira S. Datta

Matt Lux: The license was originally closed, but is now open. There are many groups working on this, e.g., sharing ontologies. There are groups working on getting these tools to talk to each other. The spirit of the community has been very open standards, open source. Things may change: there has been interest from the defense community, which is not quite as open. - Ruchira S. Datta

Eric Davidson: Much of the background work is very open, but this breaks down when you move into commercial products. E.g., there's a company around artemisinin production. A group has minimized the E. coli genome, removing pathogenicity islands, and they are not open with it. - Ruchira S. Datta

Ed Marcotte: What sorts of projects are there for open source molecules? E.g., BioBricks. Some things that are locked up, e.g., fluorescence genes, stifling the development. - Ruchira S. Datta

Matt Lux: A new registry is under development at Berkeley. Foundational parts: switches, oscillators, etc. tend to be open. But specific functions for a specific application are not very open. - Ruchira S. Datta

Larry Hunter: Is the distinction the application, or is it physical materials versus designs and software? Universities treat physical material transfer very different from software. - Ruchira S. Datta

Eric Davidson: The bricks registry is all material. The Scientific Commons is where that license is located. - Ruchira S. Datta

Matt Lux: That material is provided for all iGEM teams automatically. That's sort of a unique case. It's becoming easier to synthesize things yourself, if the sequence is put up. - Ruchira S. Datta

Ed Marcotte: But you still have to respect the intellectual property. - Ruchira S. Datta

Gil Alterowitz: Talked with iGEM. The transfer of materials is restricted to undergraduate teams, and is not open to industry groups. Also each team must pay, so it's not free [in the sense of free beer]. So there are limitations. - Ruchira S. Datta

Gil Alterowitz: Q2d. We touched on one of the touchy issues. Maybe a company wouldn't want to publish something too early, or give all the specifications out. At the same time, each side can benefit from the other. Industry has a lot of automated infrastructure that can be very useful for academia, and academia also has strengths in terms of development and research. - Ruchira S. Datta

Matt Lux: These are fairly complicated issues. There are many ways to approach it. One idea I've heard: maybe the company wants to patent the device. But perhaps they don't want to patent the use of the device, just the selling of it. E.g., they will make a device for you and sell it to you. So far it hasn't yet been a problem in synthetic biology. My experience working with companies has been pretty open, but we're investigating a question, not producing a product. - Ruchira S. Datta

May Wang: My collaborator has been working with companies. They are very interested in reproducibility and the ability to scale it up. Academic labs work on prototyping. These are complementary strengths. It's hard for an academic lab to get to reproducibility: it requires a lot of human and material resources. - Ruchira S. Datta

Gil Alterowitz: Where do you see the future of synthetic biology in the next 5 or 10 years? E.g., in personal genomics, within that time frame you could get your whole genome for $1K. What would be a similar milestone? E.g., a couple of years ago people said the counter. Two counters came out of Boston University, starting from an iGEM project, working on it a bit more, another group finished it. - Ruchira S. Datta

Matt Lux: There is a lot of buzz about synthetic biology, and people think things will happen very soon. But things are a lot more difficult than people seem to be expecting. E.g., an oscillator just came out in 2009, but the model for it was first published in 2000. It takes multiple years. - Ruchira S. Datta

Ed Marcotte: On the other hand, at RECOMB Satellite meeting, Jeff Hokie (sp?) presented synthetic half chromosome in yeast. They were able to substitute their half chromosome into yeast, and the yeast tolerated it fairly well. That seems to be a game changing crux point. - Ruchira S. Datta

Gil Alterowitz: There are two approaches, bottom-up and top-down. The top-down one is going pretty quickly. The Venter group published first artificial organism, which required putting together a lot of segments. - Ruchira S. Datta

Matt Lux: That's a good example. It goes the other way. Jeff makes modifications to the chromosome, but he's not creating a new circuit on the chromosome that does something different. - Ruchira S. Datta

Ed Marcotte: But isn't that the hardest part? - Ruchira S. Datta

Matt Lux: It's a lot harder to make the circuits do what you want them to do. Delivering them into the system has proceeded more quickly than expected. - Ruchira S. Datta

Ed Marcotte: This is a gap that needs to be addressed. - Ruchira S. Datta

Eric Davidson: Getting from design to implementation is currently work. Will need to modify existing proteins with protein engineering. Metabolic engineering will make progress. - Ruchira S. Datta

Matt Lux: Metabolic engineering is in that gap. - Ruchira S. Datta