20.109(F14) M1D2

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9/9/14  

What’s  so  important  about  rDNA?   DNA  Engineering   20.109(F14)   M1D2  Lecture   09.11.14   Natalie  Kuldell  

GeneHcs  

What’s  so  important  about  rDNA?   •  Protein   overproduc.on   •  Metabolic   engineering  $   compounds   •  DNA  and  RNA   research   •  change  genotype  of   an  organism   •  correct  gene.c  defect  

Mod 1 DNA Engineering

Molecular  GeneHcs  

IntroducHon  to  RestricHon  Enzymes   •  •  •  • 

Molecular  GeneHcs  

What  are  they?   Where  do  they  come  from?   What  do  they  do  there?     How  do  cells  protect  themselves  from   themselves?  

What  are  RestricHon  Enzymes:   Molecular  VisualizaHon   •  hUp://youtu.be/ aA5fyWJh5S0    

  •  From  knowing  to  doing   •  Advanced  PracHce  

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RestricHon  Enzymes:  what  is  their   natural  biological  funcHon?  

Where  do  restricHon  enzymes  come  from?  

•  hUp://youtu.be/ sLkZ9FPHJGM  

Proc  Natl  Acad  Sci  U  S  A.  Dec  30,   2008;  105(52):  20705–20710.     Watson,  Myers,  Caudy,  Witkowski  “rDNA:  genes  and  genomes”  

How  cells  protect  themselves  from   their  own  restricHon  enzymes?  

IntroducHon  to  RestricHon  Enzymes   •  •  •  • 

What  are  they?   Where  do  they  come  from?   What  do  they  do  there?     How  do  cells  protect  themselves  from   themselves?  

  •  From  knowing  to  doing   •  Advanced  PracHce  

RestricHon  Enzymes:     from  knowing  to  doing   •  In  PracHce   –  RecogniHon  seq  lengths   –  Types  of  cuUers   –  Shared  recog  sequences   –  Shared  overhangs   –  Buffer  condiHons   –  Storing  and  diluHng   –  Specificity   –  Lack  of  acHvity  

•  PI  for  an  hour   –  AnHcipaHng  piialls   –  Sejng  up  helpful  controls  

RestricHon  Enzymes:     from  knowing  to  doing   •  In  PracHce   –  RecogniHon  seq  lengths   –  Types  of  cuUers   –  Shared  recog  sequences   –  Shared  overhangs   –  Buffer  condiHons   –  Storing  and  diluHng   –  Specificity   –  Lack  of  acHvity  

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PI  for  an  hour….  

Bird’s  eye  view  of  gel  electrophoresis  

•  Kanamycin  resistance   gene  is  ~1000  bp  and   comes  from  a  plasmid   you  know  very  liUle   about…   •  pSC101  is  ~9200  bp  and   is  named  amer  Stanley   Cohen  (early  DNA   engineer  &  Lasker  prize   winner)    

AlternaHve  Strategy  

AlternaHve  Strategy  

•  Golden  Gate  Assembly   BsaI"

Watson,  Myers,  Caudy,  Witkowski  “rDNA:  genes  and  genomes”  

•  Gibson  Assembly  

GGTCTCNNNNNN! CCAGAGNNNNNN!

  PCR&linearized"des0na0on"vector"

PCR"product" partA(

partA(

Simultaneous/" one&pot"

partA(

BsaI/" Ligase"

Summary  

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