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[[SynBERC | back to SynBERC on OWW]]
[[SynBERC | back to SynBERC on OWW]]


'''The is a draft list of research topics that the SynBERC Chassis Thrust is considering for support.'''  <br>
'''This is a draft list of research topics that the SynBERC Chassis Thrust is considering for support.'''  <br>
<font color="red">'''Please feel free to contribute & edit.'''</font><br>
<font color="red">'''Please feel free to contribute & edit.'''</font><br>
Join the [[List:Synberc-chassis|mailing list]]!
=Conference Calls=
#[[SynBERC:Chassis:13Dec06Call|13 December 2006 SynBERC Devices Call]]


=Chassis Goals=
=Chassis Goals=
Quantitative specs/measures/milestones
Quantitative specs/measures/milestones


==Goal 1 Components to be changed==
==Goal 1 Components to be changed (quantitative goals in parens)==
* Pathway removal (for more promoters) : # paths = 2  
* Pathway removal to free up more promoter types : (# paths = 2)
* Cell heterogeneity (e.g., ara transporter) : variance (x0.7)
* Cell heterogeneity -- e.g., ara transporter  : (variance x0.7)
* Code changes : #aa (2), # phage (10) & resistance level (x100)
* Genetic code changes  
* Introduce novel chemistries into cells : sup efficiency (x1.5)
** # 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 ==
==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)
* 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)
* Mutationally inactivate insertion elements & transposons : (mutation rate x0.1) Kristala


==Goal 3  Additional chromosome(s)==
==Goal 3  Dedicated DNA, RNA & protein synthetic systems ==


* Isolate exogenous gene function from native chromosome: I/O transfer function for main/plasmid/BAC  
* Isolate exogenous gene function from native chromosome: I/O transfer function for main/plasmid/BAC  
* Origin: Partition, Addiction : loss rate  (x0.3)
* Origin: Partition, Addiction : (loss rate  x0.3)
* Improved recombination (x2)
* Improved recombination (x2)
* [[Endy:Dedicated_systems|Dedicated RNA & protein systems]]: (efficiency >10%, crosstalk <10%)
* [[Endy:Dedicated_systems/Virtual_machines| Virtual Machines]] & [[Endy:Translation_demand|Demand specifications]]


==Goal 4 Safety controls on the chassis ==
==Goal 4 Safety controls on the chassis ==
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* Delete surface toxins (Lps) : quant sepsis, innate imm.  (x0.1)   
* Delete surface toxins (Lps) : quant sepsis, innate imm.  (x0.1)   
* Low conjugation (Express TraS and TraT) : escape rate (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)  
* 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)
* Remove antibiotic resistance genes : [http://en.wikipedia.org/wiki/Minimum_inhibitory_concentration MIC] (x0.1)




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#Maximal Cells -- combinatorial selections
#Maximal Cells -- combinatorial selections


=Chassis support for [[SynBERC:Testbeds|Testbeds]]=
=Chassis support for [[SynBERC:Testbeds|Testbeds]] and [[iGEM]]=
#[[Tumor Destroying Bacteria]]
#[[Tumor Destroying Bacteria]]
#[[Microbial Drug Factories]]
#[[SynBERC:Drugs | Microbial Drug Factories]]
#iGEM: [[Tk:E._coli_cut_sites|SpeI/XbaI sites]] TK


=Chassis Characterization, Screening & Tuning=
=Chassis Characterization, Screening & Tuning=
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# Scaleable [[SynBERC:Parts|Parts]] & [[SynBERC:Devices|Devices]] Screening & Selection Platforms
# Scaleable [[SynBERC:Parts|Parts]] & [[SynBERC:Devices|Devices]] Screening & Selection Platforms
# Sequencing Platforms : [http://arep.med.harvard.edu/Polonator/ Polonies]
# Sequencing Platforms : [http://arep.med.harvard.edu/Polonator/ Polonies]
# Assembly Platform: COG
# Programming Cells Instrumentation: GE-MASS


=Societal Impact=
=Societal Impact=
* Safety – clinical, accidental, threat  [http://arep.med.harvard.edu/SBP/Church_Biohazard04c.htm  A Synthetic Biohazard Non-proliferation Proposal]
* Safety – clinical, accidental, threat  [http://arep.med.harvard.edu/SBP/Church_Biohazard04c.htm  A Synthetic Biohazard Non-proliferation Proposal]


* Surveillance – International Consortium for Polymer Synthesis (ICPS): [http://www.codondevices.com/ Codon Devices], [http://www.blueheronbio.com/ Blue Heron], etc.
* Surveillance – International Consortium for Polynucleotide Synthesis ([http://pgen.us/ICPS.htm  ICPS])
 


=Other Related Items=
=Other Related Items=
*[http://arep.med.harvard.edu/SBP/ Harvard Constructive Biology Projects]
*[http://arep.med.harvard.edu/SBP/ Harvard Constructive Biology Projects]
*[[SynBERC:Chassis/Team]]
*[[SynBERC:Chassis/Team]]
*[[Standard_E._coli_Strain_for_BioBricks|Standard ''E. coli'' Strain for BioBricks]]

Latest revision as of 05:37, 9 July 2008

back to SynBERC on OWW

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

Join the mailing list!

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

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

  • Surveillance – International Consortium for Polynucleotide Synthesis (ICPS)

Other Related Items