A quick recap of GenScript 1st Double Helix Symposium

Last Monday, September 30th, 2019, GenScript had the honor of hosting our 1st Double Helix Symposium in downtown San Francisco! Over 150 scientists, thought-leaders and industry partners convened to communicate research interests, share ideas and concepts, and discuss data and results, on technologies and applications of DNA, RNA, and protein. Our honorable speakers included Christopher Bahl, George Church, Rhiju Das, Shawn Douglas, Michael Fero, Nathan Hillson, Possu Huang, Sri Kosuri, Jin Billy Li, Lynn Rothschild, Eric Wang and Cedric Wu.

The morning speakers shared some common interests in G protein-coupled receptors (GPCRs), de novo protein design, computational methodology, synthetic biology, and their therapeutic applications.

Christopher Bahl, Ph.D., Head of Protein Design at Institute for Protein Innovation (IPI), Harvard Institutes of Medicine, kicked off the symposium by elaborating his approach using combined computational design and directed evolution, to develop novel and thermostable G alpha mimetic proteins, which selectively bind to active state of GPCRs and many different GPCRs. These de novo designed mini-proteins close the gap between small molecules and monoclonal antibodies, and offer both specificity of antibodies and high stability and manufacturability of small molecules.

The next speaker was Possu Huang, Ph. D., an Assistant Professor of Bioengineering at Stanford University. Possu created RosettaRemodel, which has been used to create most of the de novo designed proteins to date. Possu presented his de novo protein design of repeat proteins that enable LEGO-style molecular assembly. These repeat proteins self-assemble to result in superantigens with stable structures such as totorid and TIM barrel, and can non-specifically activate large subsets of T cells, shedding light on alternative cancer immunotherapies other than expensive CAR-T therapies.

Possu utilizes machine learning techniques to classify and model protein structures while Chris develops mini-proteins to bind GPCRs, Sri Kosuri, Ph.D., co-founder and CEO of Octant Bio, has built, optimized, and scaled a platform, and focused this platform on mapping chemical interactions with GPCRs. Sri introduced Octant platform technologies: receptor depth, chemical depth, synthetic biology, informatics and machine learning. Very excitingly, Octant Bio is open-sourcing some of these tools this week! Sri is a Searle Scholar (2015), NIH New Innovator (2014).

Next up was Nathan Hillson, Ph.D., who is the Director of Synthetic Biology Informatics at Joint BioEnergy Institute, U.S. Department of Energy (DOE). While Sri's platform can be used to design, build, and test large libraries of gene circuits, the key to the mission, goal, and success of the Agile BioFoundry (ABF) is the integration of Design, Build, Test, and Learn activities. Nathan presented the goal of ABF, which is to "enable biorefineries to achieve 50% reduction in time to bioprocess scale-up (as compared to the current average of ~10 years)" and "productionize synthetic biology".

I had an opportunity earlier this year to conduct a Podcast interview with Nathan, in which Nathan reviewed a publication- Parallel Integration and Chromosomal Expansion of Metabolic Pathways, and described the role of ABF in developing a public infrastructure on which private companies can then address specific problems.

During lunch, I chatted with Bobby Dhadwar, Ph.D., Associate Director, Cell Line Development at Memphis Meats. We discussed how Memphis Meats is growing cell-based meat, so no slaughter is needed to harvest the meat. Memphis Meats has been featured on WSJ, Bloomberg, NBC, JAMA, the Economist, and some other media. The company hopes to start selling its products by 2021. We also talked about the Intelligence Squared Debate that Lynn Rothschild, Ph.D., and George Church, Ph.D., had in February, "Don't Bring Extinct Creatures Back to Life", which is relevant to two of our afternoon speakers.

The afternoon speakers focused on the future of science, citizen science, as well as open access and education.

Lynn arrived right in time for her talk in the afternoon. She enthusiastically introduced her iGEM team- Team Brown Stanford Princeton, and elaborated the needs and challenges for human settlement, including upmass/upvolume, cost, storage, power and reliability & flexibility. Applications of synthetic biology can advance NASA's missions, specifically in space travel and astropharmacy. I strongly feel the future is here and synthetic biology will play essential roles in many aspects of human's future life. Feedback gathered from some attendees was that Lynn's talk was one of the most engaging talks from that day.

Following Lynn’s talk, Dr. Church gave the keynote speech, "Scripting genomes and epigenomes". It appeared that minimal introduction was needed, as everybody is aware that Dr. Church is the key opinion leader in Genetics and a pioneer in genome editing. Dr. Church reviewed the changes in cost and time of gene synthesis, and the advances in reading and editing genes. He mentioned the book he co-authored with Ed Regis, "Regenesis", and I was fascinated by the idea of bringing back a Jurassic park when I read the book in the summer.

Furthermore, FAB LAB, iGEM, GP-Write, pgEd/map-ed.org were introduced to show how to make/grow almost anything! I joined 21k+ quiz participants and pinned myself on the interactive map of Map-Ed.

Dr. Church has been an advocate of open education and open access of sequencing hardware and shareable human medical data. At the same time, he strongly supports citizen science in synthetic biology and personal genomics, and has hosted annual Genomes Environments Traits (GET) conferences. Similarly, Rhiju Das, Ph.D., an Associate Professor at Stanford University, engages hundreds of thousands of volunteer video game players in RNA fold and design, to develop predictive algorithm with a video game called EteRNA. Rhiju described to our audience the uniqueness of EteRNA and recent achievements that potentially can be applied to point-of-care diagnostics.

Another speaker from Stanford University was Jin Billy Li, Ph.D., an Associate Professor who is deeply interested in RNA editing and modifications. Dr. Li presented his current focus on Adenosine-to-Inosine (A-to-I) RNA editing, which is an important post-transcriptional mechanism critical for life, catalyzed by ADAR enzymes. ADAR1 is one of the ADAR family members identified as a new immuno-oncology target. In the afternoon session, Shawn Douglas, Ph.D., an Assistant Professor at UCSF, talked about his efforts to create DNA origami nanostructures to overcome technical challenges with cryo-EM.

Besides our invited speakers, Eric Wang and Cedric Wu, Ph.D. from GenScript gave two presentations on the main stage. Eric addressed "Easier working with DNA for the future of science", and introduced MolecularCloud platform and Cloud Scientist program, which promote communication and sharing among scientists. In addition, Eric presented the Cloud Scientist Award to Nathan Hillson, Ph.D., as the Distinguished Research Cloud Scientist.

Cedric introduced our new service- Precision Mutant Library, and concluded the day after Poster Flash Talk session, in which two young scientists, Yusuke Sasaki from Joint BioEnergy Institute and Maria Orozco Hidalgo from Lawrence Berkeley National Laboratory presented their work.

It was a day of conversations, and I am truly grateful to all of the speakers, attendees, volunteers and colleagues who participated in this symposium. My take-home message is multidisciplinary approaches and interests will continue to advance biology: machine learning, artificial intelligence, computational modeling, and engineering will weigh more in driving innovations and improving understandings in life science, which in return, will shape the future of science.