SynBERC:Chassis

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

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=Conference Calls=
 * 1) 13 December 2006 SynBERC Devices Call

=Chassis Goals= Quantitative specs/measures/milestones

Goal 1 Components to be changed (quantitative goals in parens)

 * Pathway removal to free up more promoter types : (# paths = 2)
 * Cell heterogeneity -- e.g., ara transporter : (variance x0.7)
 * Genetic code changes
 * # of codon changes (314 UAG to UAA)
 * # of novel phage restistances (10) & resistance level (x100)
 * Introduce novel chemistries into cells :
 * Amber suppressor efficiency (x1.5)
 * # of additional amino acids beyond 21 (+2)

Goal 2 Chassis 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) Kristala

Goal 3 Dedicated DNA, RNA & protein synthetic systems

 * 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)
 * Dedicated RNA & protein systems: (efficiency >10%, crosstalk <10%)
 * Virtual Machines & Demand specifications

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) ChrisV
 * Remove antibiotic resistance genes : MIC (x0.1)

=Chassis Models=
 * 1) Translational fidelity and pausing in novel genetic codes
 * 2) Recombination and DNA synthesis forks
 * 3) Minimal Cells
 * 4) Maximal Cells -- combinatorial selections

=Chassis support for Testbeds and iGEM=
 * 1) Tumor Destroying Bacteria
 * 2) Microbial Drug Factories
 * 3) iGEM: SpeI/XbaI sites TK

=Chassis 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
 * 5) Assembly Platform: COG
 * 6) Programming Cells Instrumentation: GE-MASS

=Societal Impact=
 * Safety – clinical, accidental, threat A Synthetic Biohazard Non-proliferation Proposal


 * Surveillance – International Consortium for Polynucleotide Synthesis (ICPS)

=Other Related Items=
 * Harvard Constructive Biology Projects
 * SynBERC:Chassis/Team
 * Standard E. coli Strain for BioBricks