7 June 2019, Charlottesville: Mid-Atlantic Synthetic Biology Symposium

[Daniel-Mietchen]

The agenda is in this Gdoc, and there is this overview page.

Organized by SynBio@UVA

No slides shared, nobody seems to be tweeting on this

[Daniel-Mietchen]

Steven Zeichner, UVA: Synthetic Biology Approach to Novel Vaccine Development https://tools.wmflabs.org/scholia/author/Q64447346

• collaborates with Peter Kwong (NIH) around structural context of Membrane Proximal External Region (MPER) of immunogenic proteins with potential to be used in vaccination

[Daniel-Mietchen]

Myriam Cotten, William & Mary: Identifying Principles in Peptide Engineering: Lessons Learned from the Amazing World of Host-Defense Peptides https://tools.wmflabs.org/scholia/author/Q64447649

• plug for solid-state NMR facility at W&M, inviting collaboration
• peptide antibiotics in mast cells of fish
• piscidines
• copper as mediator of antimicrobial action via p3 binding of DNA backbone; collaborated with Ruth Nussinov at NCI

[Daniel-Mietchen]

Fengbin "Jerry" Wang, Egelman Lab, UVA: CryoEM: A Powerful Tool for Understanding Biological and Synthetic Polymers

• PDB on first slide as the end point of their protein structure determination workflow
• "if you can do high-resolution Cryo-EM, you d not need to much prior knowledge to determine protein structure"
• type IV pili in bacteria and arachaea
• Geobacter nanowires

[Daniel-Mietchen]

Mike Timko, UVA: Metabolic Engineering for Plant Based Human Therapeutics

• canceled for family emergency
• https://tools.wmflabs.org/scholia/author/Q57077921

Hai Liu (not on the program): Smart Metabolic Engineering of Plants for the Production of Human Nutraceuticals and Therapeutics

• looking at primary and secondary metabolism in plants as the source of molecules of interest to humans
• astaxanthin is one of the most antioxidants found in nature but supply can currently not really meet demand
• cloning some genes from astaxanthin-producing organisms (Adonis aestivalis) into easily culturable organisms like tobacco, hemp, bacteria or yeast
• similar approach to producing human milk oligosaccharides (derived from lactose) in plants for women who cannot breastfeed (enough)
• question from audience: "given the range of synbio you are engaged with, is there a company that does this at scale, similar to what Ginkgo Bioworks does?" response from audience: "It used to be called Monsanto, which is now Bayer"

[Daniel-Mietchen]

Deyu Xie, NC State: Gene Design-based Alteration of the Terpenoid Pathway Increases Plant Growth and Biomass

• 5 min lost switching computers
• very happy that preceding talk was highlighting plants
• starts with a plug for the Plant Sciences Initiative at NCSU
• comments on the difficulty to get work on secondary metabolism in plants funded, since "secondary" is perceived as "unimportant" by those who do not know much about how plants work
• about 50,000 terpenoids https://tools.wmflabs.org/scholia/topic/Q426694
  • e.g. isoprene https://tools.wmflabs.org/scholia/topic/Q271943
• can isoprene (which protects plants against heat, contributes to the blue sky above mountain forests and can be "seen" especially well after a short thunderstorm) be captured at scale?
• tobacco plant biomass about doubled when isoprene was captured

[Daniel-Mietchen]

Ameer Shakeel, CSO of Agrospheres: Synthetically Engineered Solutions for Bio-Controls in Agriculture

• more time lost switching computer
• working on degrading pesticides, since pesticide is an issue both worldwide and locally (e.g. in vineyard)
• small-scale tests showed that pesticides can be degraded within hours
• much of pesticides is not reaching the plants anyway
• encapsulate pesticides into "AgriCells" which allow for controlled release
• AgriCells are engineered by tweaking bacterial division such that the centromer as at the apex, not the center, which gives nice spherical variants of rod-shaped bacteria
  • about 1 in two bacterial divisions creates such a minicell
  • they have issues harvesting the minicells from dishes, so now working on flow-based techniques
• trying to replace synthetic pesticides with biologicals
• currently field testing with ADAMA
• greenhouse testing facilities
• Mark Kester (one of the symposium organizers) is an early investor in the technology

[Daniel-Mietchen]

Ed Eisenstein, UMD: Systems, Structural and Synthetic Biology to Develop Next-Gen Plants for Biofuel

• https://tools.wmflabs.org/scholia/author/Q28359814
• cellulose and lignin are
  • some of the most common polymers on the planet
  • closely intertwined in plant structures, but
  • humans have a strong interest in cellulose (chiefly for biofuel) but low interest in lignin
• idea: can the metabolic pathways that produce lignin/ cellulose be (re-)engineered such that cellulose can be more easily harvested (and ideally more of it)?
• promising preliminary results, details to be worked out
• multiple shout outs (by him and previous speakers) to iGEM

[Daniel-Mietchen]

Keynote Speaker: Dr. Pam Silver, Harvard University Wyss Institute of Biologically Inspired Engineering

Designing Biology for Health and Sustainability

• lots of accolades, including co-founder of iGEM
• https://tools.wmflabs.org/scholia/author/Q7129257
• How can we identify [engineering] problems that biology can help solve?
  • sounds like molecular bionics to me
• introduction about phage lambda
• bionic leaf
• "the gut is an amazing place"
• over US$ 10 billion are used each year on colonoscopies in the US
• probiotic pill to diagnose diarrhea using gut microbiome
• tetrathionate as an indicator of inflammation
• Sedlmayer and Fussenegger 2017, USB stick with multiple bacterial biosensors
• criticizes the non-GMO movement and plans to open an "All-GMO" restaurant
• "bug in a pill"
• total genome resynthesis
• book "the informer" on infection
• microbial kill switch
• artificial chromosome
  • key challenge: how to build a synthetic centromere
  • human artificial chromosomes can be delivered (along with proteins) to mammalian cells through yeast cells
  • big idea: for extreme use cases (e.g. severe injuries), it would be great if there were mechanisms to help, e.g. proteins from extremophiles
• imagine cells that had 10 fluoresence markers or that were to express a 1000 antigens on their cell surface
• "anticipatory therapeutics" - sounds to me like prophylaxis

[Daniel-Mietchen]

iGEM 2019 is Oct 31- Nov 4 in Boston: https://2019.igem.org/ . UVA has a team participating.

[Daniel-Mietchen]

Steven Fong, VCU: Engineering Non-Model Organisms for Biochemical Production

• self-described "microbial chauvinist"
• likes to think of the ca. 8.7 million (or whatever) species and consider their diversity and how it can be leveraged in different contexts
• high hopes for microbes in this regard
• Thermobifida fusca: to turn cellulose into propanol
  • https://tools.wmflabs.org/scholia/topic/Q21311775
• barriers for working with non-model systems
  • how to build genetic workflows to transform it
• used enzymes that could handle several steps of a metabolic pathway
• Serratia marcescens
  • breaks down chitin
  • naturally resistant to some typical antibiotics

[Daniel-Mietchen]

Bryan Berger, UVA: Biomanufacturing of Advanced, Functional Nanomaterials

• introduces quantum dots as being
  • interesting in a number of contexts
  • expensive to manufacture
  • $1k-10k per gram
• then introduces Stenotrophomonas maltophilia as a potential system to manufacture quantum dots, i.e. size-controlled conductive nanomaterials
• engineering proteins that could in principle catalyze all steps of a given pathway
• artificial photosynthesis
• next candidate: silicatein alpha - can this be synthesized bottom-up?
  • PDB 2VHS
• nanoceria catalysts (used in catalysts in cars)
• got production costs down to about $10-$100 per gram using biosyntheis

[Daniel-Mietchen]

Preetam Ghosh, VCU: Information Theory Models of Molecular Communication and Cellular Signaling

• running fast-forward loops around the Lac operon by the thousands
• sounds like metabolic control theory at scale

[Daniel-Mietchen]

Hannes Schniepp, William & Mary: Unlocking the Mysteries of a Biogenic Wonder Material: Understanding Spider Silk from the Molecular to the Meter Scales

• https://tools.wmflabs.org/scholia/author/Q47986821
• touts silkworm silk a "7000 year-old synbio success story", and until about WW2, the best material of its kind
• then introduces spider silk, which is even more amazing, e.g. compared to steel and kevlar
• interested in use cases like bullet-prove vests
• considers biotechnological workflows to produce spider silk
• structure of spider silks not well known
• model system: Loxosceles laeta
  • ribbon structure
  • consists to 100% of nanofibrils
• Nephila clavipes
• "We can make spider silk from protein!"
• comment from audience: someone from Tufts has determined that spider protein is "intrinsically disordered", with folding patterns thus depending much on context

[Daniel-Mietchen]

Mark Styczynski, GA Tech: Low-Resource, Low-Cost Diagnostics Via Synthetic Biology

• bacteria-based tests for micronutrient deficiencies (zinc specifically, which kills about 100k kids under 5 each year) in low-cost settings
• coupled Lac operon with Zinc-responsive elements in cell-free system produced in E. coli that were then lyzed
• key issue is calibration
• need standards
• "saturate the biomarker and vary the regulator"
• generalizing from Zinc to other micronutrients

[Daniel-Mietchen]

Key take-aways:

• lots of exciting science
• lots of things relevant to protein structure
• not much openness
• would benefit from interaction with data science
• iGEM is an interesting model to look at in terms of engaging the next generation