Graduate Student - Ph.D.

Chemistry

Physics

University of Illinois at Urbana-Champaign (Urbana, IL)

Yann R Chemla

Use of a variety of single molecule spectroscopic methods to study the way sequence-specific DNA binding proteins find their DNA recognition sequences.

Protein-DNA interactions lie at the heart of many essential cellular processes such as replication, recombination, and repair. Recent advances in optical “tweezers” have made it possible to resolve motions on the scale of a single base pair of DNA, 3.4Å. These high-resolution optical traps have the potential to reveal these interactions at their fundamental length scales and should reveal how certain proteins bind to DNA or recognize target sequences.

Telomerases are enzymes that have been actively studied in various organisms because of their fundamental involvement with both cancer and aging. There are a variety of different telomerase enzymes whose broad function is to protect the integrity of chromosomal ends by various different means. In prokaryotic organisms, the study of DNA hairpins has proven to be particularly important. DNA hairpin structures regulate gene expression, and therefore play an active role in protecting DNA and controlling mutagenesis. Protelomerase TelK is an enzyme responsible for forming closed DNA hairpin ends in linear DNA, however, the mechanism by which it does so is still unclear.

One model proposes that the TelK-DNA complex forms a cruciform transition state prior to cleavage. The study of this enzyme also provides unique views into the importance of electrostatic interactions as gateways to overcome high energy barriers of substrate formation. TelK is not an ATP dependant enzyme, which is surprising given the degree of DNA distortion accomplished by the enzyme, and the large energy barrier intrinsic in DNA hairpin formation. For this reason, we are working with TelK mutants (TelK YF) with a single amino acid mutation at the active site (Tyrosine to Phenylalanine). We are also working with a c-truncated mutant, TelK538, a TelK derivative that lacks its c-terminal domain. Measurements using high-resolution optical tweezers should offer an unambiguous conclusion as to the correct transition state, and fundamental insights into the nature and importance of the electrostatic interactions between TelK and its DNA substrate.

2010 Lindau Meeting of Nobel Laureates, U.S. Student Delegate

2009-2012 NSF Graduate Research Fellowship

2009 NSF / JSPS EAPSI Fellowship

2008-2009 NSF Center for Physics of Living Cells Fellowship