Dr. Sarah E. Walker
Office: Hochstetter 653
Office Hours: TBD
Tel: (716) 645-2272
Ph.D. The Ohio State University
Postdoctoral Research at Johns Hopkins University at the National Institutes of Health
Translational Control of Gene Expression
Regulation of translation initiation allows rapid and precise changes in gene expression in response to changing cellular and external conditions. A well-characterized, but poorly understood mode of translational control is the epigenetic modification of translation initiation factors, which is thought to modulate the functions of initiation factors that promote translation complex assembly at the start codon. Understanding the conserved mechanisms of epigenetic control over translation carries important implications, as modifications of initiation factors are prevalent in eukaryotic organisms, and misregulation of initiation factor modification in mammals has profound effects in perpetuating disease states. We aim to understand the molecular basis for translational control by investigating the underlying mechanics of translation and effects of epigenetic modifications of the yeast translation apparatus, using both directed biochemical and genetic techniques and global surveys of conditions and proteins that promote changes in cap-dependent translation.
Identification and characterization of functionally critical, conserved motifs in the internal repeats and N-terminal domain of yeast translation initiation factor 4B (yeIF4B). Zhou F*, Walker SE*, Mitchell SF, Lorsch JR, Hinnebusch AG. The Journal of biological chemistry. 2014; 289(3):1704-22. PMID: 24285537
Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains.
Walker SE*, Zhou F*, Mitchell SF, Larson VS, Valasek L, et al. RNA. 2013; 19(2):191-207. PMID: 23236192
Yeast eukaryotic initiation factor 4B (eIF4B) enhances complex assembly between eIF4A and eIF4G in vivo. Park EH, Walker SE, Zhou F, Lee JM, Rajagopal V, et al. The Journal of biological Chemistry. 2013; 288(4):2340-54. PMID: 23184954
Reverse transcriptase dideoxy sequencing of RNA. Walker SE, Lorsch J. Methods Enzymology. 2013;530:347-59. PMID: 24034332.
RNA purification–precipitation methods. Walker SE, Lorsch J. Methods in enzymology. 2013; 530:337-43. PMID: 24034331
Sanger dideoxy sequencing of DNA. Walker SE, Lorsch J. Methods in enzymology. 2013; 529:171-84. PMID: 24011045
Initiation factor eIF2γ promotes eIF2-GTP-Met-tRNAi(Met) ternary complex binding to the 40S ribosome. Shin BS, Kim JR, Walker SE, Dong J, Lorsch JR, et al. Nature structural & molecular biology. 2011; 18(11):1227-34. PMID: 22002225
Recruiting knotty partners: The roles of translation initiation factors in mRNA recruitment to the eukaryotic ribosome. Mitchell, S.F., Walker, S.E., Rajagopal, V., Aitken, C.E. and J.R. Lorsch. In Ribosomes: Structure, Function, and Dynamics. 2011; ed M. Rodnina, W. Wintermeyer, and R. Green (Book Chapter).
Multiple elements in the eIF4G1 N-terminus promote assembly of eIF4G1•PABP mRNPs in vivo. Park EH, Walker SE*, Lee JM*, Rothenburg S, Lorsch JR, et al. The EMBO journal. 2011; 30(2):302-16. PMID: 21139564
The 5′-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway. Mitchell SF, Walker SE, Algire MA, Park EH, Hinnebusch AG, et al. Molecular cell. 2010; 39(6):950-62. PMID: 20864040