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【9月23日报告】RNA structural determinants of optimal codons revealed by MAGE-seq
  发布时间:2016-09-19    供稿部门:
 

  报告题目RNA structural determinants of optimal codons revealed by MAGE-seq   

  报告时间923日(周五) 14:00-15:00   

  报告地点C408   

  报告简介Synonymous codon choices at the beginning of genes optimize 5’ RNA structure for enhanced translation initiation, but less is known about mechanisms that drive codon optimization in later gene regions. To understand the determinants of codon choice across a gene, we measured the fitness of 12,726 in situ codon mutants in the Escherichia coli essential gene infA using MAGE-seq: a combination of systematic Multiplex Automated Genome Engineering mutagenesis with fitness measurements by amplicon deep sequencing. Correlating 5’ RNA structure with fitness, we find that codons even far from the start of the gene are deleterious if they disrupt the native 5’ RNA conformation. These long-range structural interactions create context-dependent rules that constrain codon preferences beyond intrinsic codon properties in infA. Genome-wide RNA folding predictions confirm that natural codon choices far from the start codon are optimized in part to prevent disruption of native structures near the 5’ UTR. Our results shed light on natural codon distributions and should improve engineering of gene expression for synthetic biology applications.   

   报告人简介 Eric Kelsic

   Work Experience
   Postdoctoral Research Fellow
, Wyss Institute, Harvard Medical School, Boston MA, (2015-present)
    • Developing gene therapy technologies in lab of Prof. George Church

   PhD in Systems Biology, Harvard University, Cambridge MA, 2008-2015
   • Research in the lab of Prof. Roy Kishony
       o Discovered that 3-way species interactions enable antibiotic producing, resistant and sensitive species to coexist; developed experimental assays to measure these interactions
       o Developed MAGE-Seq, a method for high-throughput and systematic genome editing and phenotyping; analyzed data from an essential gene to decipher key features of optimal  codon  usage and protein function 
   English instructor, Nankai University, Tianjin China, 2007-2008
   • Taught 6 classes in speaking and writing to English majors (100 students)
   Puzzle box inventor, Longmont CO, 2000-2002
   • Designed, constructed and marketed wooden puzzle boxes to collectors world-wide
   Selected Awards
   • 2009-2012: National Defense Science and Engineering Graduate (NDSEG) Fellowship

   Publications
   A Traud, ED Kelsic, P Mucha, M Porter. Comparing Community Structure to Characteristics in Online Social Communities. SIAM Review. September 2011
  ED Kelsic. Systematic approaches to deciphering genes and ecosystems. PhD Thesis, Systems Biology, Harvard University. January 2015
  ED Kelsic, J Zhao, K Vetsigian, R Kishony. Counteraction of antibiotic production and degradation generates stability in microbial communities. Nature, May 2015
  E Bairey, ED Kelsic, R Kishony. High-order species interactions shape ecosystem diversity. Nature Communications, August 2016
  M Baym, TD Lieberman, ED Kelsic, R Chait, R Gross, I Yelin, R Kishony. Spatiotemporal microbial evolution on antibiotic landscapes. Science (in press)
  ED Kelsic*, H Chung*, N Cohen, J Park, HH Wang, R Kishony. RNA structural determinants of optimal codons revealed by MAGE-seq. Cell Systems (in press)

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