Molecular Biology, Structural Biology
University of Colorado Boulder
Dr. Luger holds the Jenny-Smoly-Caruthers Endowed Chair of Chemistry and Biochemistry at the University of Colorado, Boulder.
Structure and Dynamics of Chromatin
DNA carries the fundamental genetic information essential to life—but it is hardly a solo performer in the cell's nucleus. In fact, its billions of base pairs are tightly packed together with proteins into a complex called chromatin, whose structure controls whether the cell can transcribe genes and replicate and repair DNA.
Scientists like Karolin Luger are constantly angling for better images of this central structure, and early in her career, she snapped one of the best. In 1997, Luger and her colleagues used x-ray crystallography to reveal the structure of a core chromatin particle with unprecedented detail. This work not only demonstrated how structural aspects of chromatin guide its role in DNA transcription, replication, and repair, but has also provided the foundation for further studies by others in the chromatin field.
Luger has used her structure of the nucleosome—a fundamental chromatin component made up of a disk of proteins surrounded by DNA—as merely a starting point. Since that achievement, she has shifted her focus from what the nucleosome is to what it does.
At the most fundamental level, the nucleosome is believed to regulate access to DNA during gene transcription. Luger's more ambitious goal is to understand how the structure varies, based on changes in its own proteins or interactions with outside molecules. Ultimately, she hopes to refine the overall view of how chromatin is organized at higher levels.
To address these issues, Luger complements her structural studies with biochemical and biophysical experiments, and the results have shed light on how the nucleosome changes shape and how chromatin interacts with the cell's transcription machinery. Variations in histones—the major protein component of the nucleosome—play a significant role in regulating gene expression, and Luger is carefully characterizing how subtle changes in these proteins can affect overall nucleosome structure.
Luger's recent work has concentrated on how histone "chaperones" promote structural changes in nucleosomes and facilitate the sliding of histones along the DNA. These proteins, which were previously thought of as chaperones in the true sense of the word—in that they guide histones to the DNA and prevent them from making "improper" interactions—now appear to also have a very active role in promoting nucleosome dynamics; the chaperones have joined the dance.