SynBERC:Chassis

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The is a draft list of research topics that the SynBERC Chasses Thrust is considering for support.
Please feel free to contribute & edit.

Chasses Goals

Quantitative specs/measures/milestones

Goal 1 Components to be changed

• Pathway removal (for more promoters) : # paths = 2
• Cell heterogeneity (e.g., ara transporter)  : variance (x0.7)
• Code changes : #aa (2), # phage (10) & resistance level (x100)
• Introduce novel chemistries into cells : sup efficiency (x1.5)

Goal 2 Chasses robust to change & minimizing mutation rates

• Anti-mutator alleles of: dam, dnaEQ, mutDHLMRSTY, oxyR, polAC, recAG, ssb, topB, ung, uvrD, or vsr : mutation rate (x0.5)
• Mutationally inactivate insertion elements & transposons : mutation rate (x0.1)

Goal 3 Additional chromosome(s)

• Isolate exogenous gene function from native chromosome: I/O transfer function for main/plasmid/BAC
• Origin: Partition, Addiction : loss rate (x0.3)
• Improved recombination (x2)

Goal 4 Safety controls on the chassis

• Delete phage lysogens & receptors (e.g. LamB) : resistance level (x100)
• Delete surface toxins (Lps) : quant sepsis, innate imm. (x0.1)
• Low conjugation (Express TraS and TraT) : escape rate (x0.1)
• Add complicated or rare auxotrophies to prevent survival outside the lab (aTc-tetR, Dap) : t1/2 = 1 to 90hr; escape % (x0.01)
• Remove antibiotic resistance genes : MIC (x0.1)

Chasses Models

1. Translational fidelity and pausing in novel genetic codes
2. Recombination and DNA synthesis forks
3. Minimal Cells
4. Maximal Cells -- combinatorial selections

Chasses support for Testbeds

1. Tumor Destroying Bacteria
2. Microbial Drug Factories

Chasses Characterization, Screening & Tuning

1. Test Constructs for Characterization
2. Models that Support Data Analysis
3. Scaleable Parts & Devices Screening & Selection Platforms
4. Sequencing Platforms : Polonies

Societal Impact

• Safety – clinical, accidental, threat A Synthetic Biohazard Non-proliferation Proposal

• Surveillance – International Consortium for Polymer Synthesis (ICPS): Codon Devices, Blue Heron, etc.

Other Related Projects

Harvard Constructive Biology Projects