Jennifer J. Ottesen
Assistant Professor
Phone: 614-292-4525
Fax: 614-292-6773.
email: ottesen.1@osu.edu
Webpage:
Research Interests:
Research in the Ottesen laboratory utilizes peptide and protein chemistry
to address biological problems. The Ottesen group is developing improved
techniques for solid phase chemical ligation, which allows the rapid
recombination of peptide elements into larger macromolecules. They also
employ expressed protein ligation, in which synthetic polypeptides and
recombinant protein elements can be chemoselectively linked together.
This allows the power of synthetic techniques to be applied to large
proteins.
Initial projects in the Ottesen lab focus on understanding basic aspects
of nuclear transport, which is a fundamental element of cellular function
and a potential therapeutic target in cancer. The nuclear pore complex
(NPC) is the only gate between the cytoplasm and the nucleus of the
cell, and controls movement of large proteins across the nuclear membrane.
The interior of the pore is lined with proteins that are characterized
by long, unstructured regions containing multiple Phe and Gly-rich repeat
sequences (FG repeats). These proteins (FG-nucleoporins) mediate transport
of specific proteins through the nuclear pore. Dr. Ottesen and her research
team are particularly interested in proteins that interact directly
with the FG-nucleoporins and cross the pore without the aid of carrier
proteins. Examples of such proteins are members of the Smad protein
family, which mediate signal transduction in the TGF-beta pathway, and
STAT1, which mediates signal transduction in the JAK/STAT pathway.
The Ottesen lab is working to define general rules for karyopherin-independent
nuclear transport. Currently, a systematic study is underway to determine
how substitutions within the FG repeat cores, intervening residues,
and surrounding regions modulate the affinity of FG repeats for their
binding partners, and how the number and spacing of repeats affects
FG-nup binding (avidity effects). This information will be used to design
high-affinity FG mimics that can intercept particular import and export
pathways.
Publications
Selected publications from the last several years:
Ottesen, J.J., Huse, M., Sekedat, M.D., Muir, T.W. (2004) "Semisynthesis
of phosphovariants of Smad2 reveals a substrate preference of the activated
T beta RI kinase." Biochemistry 43(19), 5698-706.
Cowburn, D., Shekhtman, A., Xu, R., Ottesen,
J.J., Muir, T.W. (2004) "Segmental
isotopic labeling for structural biological applications of NMR." Methods
Mol Biol. 278, 47-56.
Wilson, K.A., Kalkum, M., Ottesen, J.J., Yuzenkova, J., Chait, B.T.,
Landick, R., Muir, T., Severinov, K. and Darst, S.A. (2004) "Structure
of microcin J25, a peptide inhibitor of bacterial RNA polymerase, is
a lassoed tail." J. Am Chem. Soc. 125(41), 12475-83.
Ottesen, J.J., Blaschke, U.K. Cowburn, D. and Muir, T.W. (2003) "Segmental
isotopic labeling: Prospects for a new tool to study the structure-function
relationships in multi-domain proteins." Biol. Mag. Res. 20, 35-51.
Mezo, A.R., Ottesen, J.J., and Imperiali B. (2001) " Discovery
and characterization of a discretely folded homotrimeric betabetaalpha
peptide." J. Am. Chem. Soc. 123(5), 1002-3.
Ottesen, J.J. and Imperiali, B. (2001) " Design of a discretely
folded mini-protein motif with predominantly beta-structure." Nat.
Struct. Biol.8(6), 535-9.
Imperiali, B. and Ottesen, J.J. (1999) "Uniquely folded mini-protein
motifs." J. Pept. Res. 54(3), 177-84. (Review)
Imperiali, B. and Ottesen, J.J. (1998) "Design strategies for
the construction of independently folded polypeptide motifs." Biopolymers
47(1), 23-9.
Struthers, M., Ottesen, J.J.and Imperiali B. (1998) "Design and
NMR analyses of compact, independently folded BBA motifs." Fold
Des. 3(2), 95-103.
