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    • Genetic code expansion in model organisms
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Selected publications

Selected publications

Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal cycloaddition.. 
Nature Chem.  2012  4:298-304.
K. Lang, L. Davis, A Deiters, J.W. Chin.

The first in a series of papers that makes site-specific protein labeling in mammalian cells, via genetic code expansion and bio-orthogonal chemistry, a reality.

 

Expanding the Genetic Code of an Animal.
J. Am. Chem. Soc. 2011  133:1496-14199
S. Greiss & J.W. Chin.

The first genetic code expansion in an animal, C.elegans.  This work, and our work in Drosophila, create many new opportunities for leveraging the powerful approaches we have developed in cells to study development, disease and neurobiology in model organisms with molecular precision.

 

Traceless & Site-Specific Ubiquitination of Recombinant Proteins. 
J. Am. Chem. Soc. 2011 133:10708-10711
S. Virdee, P.B. Kapadnis, T. Elliott, K. Lang, J. Madrzak, D.P. Nguyen, L. Riechmann, & J.W. Chin.

Describes the seamless and powerful integration of genetic code expansion and native chemical ligation to site-specifically ubiquitinate recombinant proteins.

 

Light Activated Kinases Enable Temporal Dissection of Signaling Networks in Living Cells.  
J. Am. Chem. Soc. 2011 133: 2125-2127
A. Gautier, A. Deiters, & J.W. Chin.

Demonstrates a strategy for activating a single protein kinase in mammalian cells with a millisecond pulse of light.  This approach provides unique insights into both the kinetics of elementary steps in signalling and adaptive responses in signalling.

 

Engineered Diubiquitin Synthesis Reveals K29 Isopeptide Specificity of an OTU Deubiquitinase.  
Nature Chem. Biol. 2010 6:750-757
S. Virdee, Y. Ye, D.P. Nguyen, D. Komander & J. W. Chin.

Demonstrates a first route to the synthesis of atypical ubiquitin chains, and the use of protection and deprotection schemes in combination with genetic code expansion to direct site-specific protein modification. The methods reported allowed the first structure of K6 linked ubiquitin and the profiling of deubiquitnase specificity on atypical chains, revealing that TRABID preferentially cleaves atypical isopeptide linkages.

 

Encoding Multiple Unnatural Amino Acids via a Quadruplet Decoding Ribosome. 
Nature. 2010 468:441-444.
H. Neumann, K. Wang, L. Davis, M. Garcia-Alai, & J.W. Chin.

Demonstrates the evolution of an orthogonal ribosome to read quadruplet codons.  This ribosome forms the basis of a parallel genetic code in the cell that is used to genetically program a redox insensitive crosslink into calmodulin. This work demonstrates the power of creating and evolving orthogonal versions of conserved and essential cellular hubs as a route to accessing new functions.

 

A Method for Genetically Installing Site-specific Acetylation in Recombinant Histones Defines the Effects of H3 K56 Acetylation. 
Mol. Cell.  2009. 36:153-163
H. Neumann, S. Hancock, R. Buning, A. Routh, L. Chapman, J. Sommers, T. Owen-Hughes, J. van Noort, D. Rhodes, & J.W. Chin.

Demonstrates the first synthesis of histones, nucleosome core particles and defined nucleosomes arrays bearing this important post-translational modification, and demonstrates using single molecule FRET that H3K56 acetylation increases DNA breathing on nucleosomes.  This paper demonstrates the power of creating ‘designer nucleosomes’ to address problems in chromatin biology.  More broadly, it demonstrates the power of genetically installing post translational modifications for asking previously un-addressable questions about biological regulation.

 

Synthesis of Orthogonal Transcription-Translation Networks.
Proc. Natl. Acad. Sci. U.S.A. 2009. 106: 8477-8482.
W. An & J.W. Chin

Demonstrates the construction of orthogonal gene expression systems.  These systems read genes that are un-readable by the host cell.  This work illustrates  how orthogonal versions of essential cellular components can be used to create networks that can not be accesssed by natural biology, and that  orthogonal feed-forward loops can introduce long delays into gene expression that would be challenging to achieve otherwise.

 

Genetically Encoding Ne-acetyllysine in Recombinant Proteins. 
Nature Chem. Biol. 2008. 4: 232-234.
H. Neumann, S.Y. Peak-Chew & J.W. Chin.

Demonstrates for the first time that the pyrrolysyl-tRNA synthetase/tRNA pair can be evolved in the laboratory to incorporate new amino acids, and incorporates an important post-translational modification- acetyl-lysine.

 

A Network of Orthogonal Ribosome•mRNA Pairs. 
Nature Chem. Biol. 2005. 1: 159-166.
O. Rackham & J. W. Chin.

Discovers a set of orthogonal ribosomes by directed evolution, and sets the stage for ribosome evolution and unfreezing the genetic code.

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© Chin Laboratory
MRC Laboratory of Molecular Biology
Centre for Chemical & Synthetic Biology
Division of Protein and Nucleic Acid Chemistry

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