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Colorado State University biochemists receive $7.8M grant to study how chromosomes “unravel” genetic info
by Jeffrey Bouley  |  Email the author


FORT COLLINS, Colo.—With a $7.8 million, five-year grant from NIH's National Institute of General Medical Sciences (NIGMS) in their pockets to help out, a team of biochemists at Colorado State University (CSU) will investigate more fully how chromosomes allow genes to do their jobs.  
Under the leadership of professors Jennifer Nyborg, Karolin Luger and Laurie Stargell, the university will study how the basic unit that tightly packages DNA into chromosomes, known as a nucleosome, unfolds and disassembles to expose genes that give cells their biological traits.  
"Because the nucleosome plays a pivotal role in gene expression, finding ways to manipulate its assembly and disassembly are of great biological and potentially therapeutic interest," says Peter Preusch, who oversees biophysics grants at NIGMS. "With their strong scientific connections—both between each other and their subprojects—Dr. Nyborg and her colleagues are uniquely positioned to detail the mechanisms of these processes."  
"The question that we're asking is very fundamental to life, and the environment here at CSU, and in the Department of Biochemistry and Molecular Biology, gives us a significant edge," Nyborg said.  
In every living cell, bulky proteins must maneuver through the densely packed nucleosomes to access the genes so that the DNA can be copied—first into RNA and then into protein. That process occurs at thousands of genes in every cell in the body and results in giving each cell its unique instructions—for example, telling a liver cell how to be a liver cell and not a brain cell.   But scientists have limited understanding of how the cell gains access to individual genes that are tightly compacted into chromosomes, the team at CSU notes.  
"We know that nucleosomes serve to compact the DNA to fit into a cell nucleus; what remains a long-standing mystery is how genes—encoded by the DNA—are unwound from the nucleosomes to allow access for copying their instructions into proteins, with a specific biological outcome for the cell," Nyborg said. "The cell faces an enormous paradox—it must tightly wrap the DNA around nucleosomes for compaction, but at the same time it must unwrap the DNA at specific sites to turn a gene on."  
The key to this process is manipulating the nucleosomes. The cell must strategically move or remove nucleosomes from the DNA to gain access to the underlying gene.   To understand more about how genes function in their densely packed intracellular environment, the three women will tackle three separate but highly interdependent biochemistry research projects through the grant:  
Nyborg will tackle basic biochemistry that will reveal how the nucleosomes are disassembled to expose the DNA of the gene. She has developed a unique experimental system in a test-tube that resembles the process of nucleosome movement in a living cell. This system will provide a much greater understanding of nucleosome dynamics.  
Luger's experiments will focus on a protein that facilitates the assembly and disassembly of the nucleosome on the DNA. She will gain an atomic level understanding of the mechanisms that cause nucleosomes to move off the DNA when genes are turned on.
Stargell, whose specialty is yeast genetics, will study the movement of nucleosomes when genes are turned on in living cells. Although her studies will be performed in yeast, the nucleosomes are evolutionarily conserved, meaning they're the same whether they're in a yeast cell or a human cell. Her work is an essential complement to the test-tube experiments conducted in the Luger and Nyborg laboratories. Stargell's research focuses on the basic mechanisms that govern genes, which is particularly important since many human diseases (including cancer) are caused by abnormal gene regulation.
Code: E05041001



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