See attached continuation.

Public Health Relevance

Split inteins are Nature's protein ligases, mediating the traceless ligation of any polypeptide chains to which they are appended. The research program focuses on a recently discovered family of split inteins that mediate this ligation process with unprecedented speed and fidelity, creating enormous potential in protein biotechnology with applications ranging from basic molecular and cell biology to the preparation of protein therapeutics. We will determine how these proteins catalyst the ligation reaction so efficiently and then use this information to develop therapeutic strategies targeting inteins and develop new technologies for manipulating the structure and function of proteins in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37GM086868-20
Application #
9238971
Study Section
Special Emphasis Panel (NSS)
Program Officer
Wehrle, Janna P
Project Start
1999-09-01
Project End
2022-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
20
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Princeton University
Department
Chemistry
Type
Graduate Schools
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08543
Gramespacher, Josef A; Stevens, Adam J; Thompson, Robert E et al. (2018) Improved protein splicing using embedded split inteins. Protein Sci 27:614-619
Jenness, Christopher; Giunta, Simona; Müller, Manuel M et al. (2018) HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome. Proc Natl Acad Sci U S A 115:E876-E885
Wojcik, Felix; Dann, Geoffrey P; Beh, Leslie Y et al. (2018) Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants. Nat Commun 9:1394
David, Yael; Muir, Tom W (2017) Emerging Chemistry Strategies for Engineering Native Chromatin. J Am Chem Soc 139:9090-9096
Gramespacher, Josef A; Stevens, Adam J; Nguyen, Duy P et al. (2017) Intein Zymogens: Conditional Assembly and Splicing of Split Inteins via Targeted Proteolysis. J Am Chem Soc 139:8074-8077
Winer, Benjamin Y; Huang, Tiffany S; Pludwinski, Eitan et al. (2017) Long-term hepatitis B infection in a scalable hepatic co-culture system. Nat Commun 8:125
Wang, Xueyin; Paucek, Richard D; Gooding, Anne R et al. (2017) Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA. Nat Struct Mol Biol 24:1028-1038
Dann, Geoffrey P; Liszczak, Glen P; Bagert, John D et al. (2017) ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference. Nature 548:607-611
Stevens, Adam J; Sekar, Giridhar; Shah, Neel H et al. (2017) A promiscuous split intein with expanded protein engineering applications. Proc Natl Acad Sci U S A 114:8538-8543
Debelouchina, Galia T; Muir, Tom W (2017) A molecular engineering toolbox for the structural biologist. Q Rev Biophys 50:e7

Showing the most recent 10 out of 33 publications