The complex inner workings of cells, from their architecture to their signaling, underlie much of multicellular organic life. How are they built? How do their proteins interact? And most crucially, how can understanding these functions improve our knowledge of biological outcomes such as disease?

Â鶹ӰԺ Distinguished Professors Karolin Luger and Natalie Ahn have studied questions such as these for decades. Last year, both were elected to the , one of the most prestigious honors a scientist can receive. The duo will be formally inducted on Saturday, April 27 at the organization’s annual meeting.

“It’s a high honor because it comes from peers,” said Luger, the endowed chair of CU Â鶹ӰԺ’s Department of Biochemistry and a  Investigator. “It’s primarily a wonderful acknowledgement of the collective work of all the former and present students, post-docs and technicians who have contributed to this research.”

Like an archeologist piecing together the origins of ancient structures, Luger and her students examine the fundamental building blocks of genomic processes and untangle their cellular machinery.

Luger began her career with an interest in x-ray crystallography, a technique used to discern 3D molecular structures. Eventually, her focus shifted to chromatin, the material that holds DNA, RNA and proteins together in a compact package within eukaryotic cells. As recently as the late 1980s, before the advent of the Human Genome Project, chromatin was thought to be unimportant, similar to packaging material that only serves to hold more valuable items inside.

“It was a binary mentality back then, but it turned out to be much messier, with lots of variation between individual cells,” Luger said. “The packaging, so to speak, has very important implications for how cell types differentiate.”

Imagine a space filled with labeled cardboard boxes full of books, she says. By reading the labels on the boxes, humans can discern which boxes they’ll need soon and which ones they can safely stash away. Chromatin operates similarly: A fertilized egg cell needs everything—all the genomic information it can get—whereas a more mature cell, such as a liver cell, can read the packaging and know what it can safely ignore.

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Pioneering biochemists Natalie Ahn and Karolin Luger have been inducted into the , an honor that recognizes "distinguished and continuing achievements in original research." Membership in the prestigious organization is widely considered to be one of the highest honors that a scientist can receive.

"It's really a wonderful recognition of our work and a great honor that I share with all of my coworkers, past and present," said Luger, a professor in the Department of Chemistry and Biochemistry and the Jennie Smoly Caruthers Endowed Chair of Biochemistry.

Luger and her colleagues study how genetic material is stored in human cells and how these organizational principles critically affect every aspect of cell life in health and disease. Understanding and visualizing protein-DNA assemblies at atomic resolution will allow researchers to better understand how the genome is decoded by the cell’s machinery.

In 2017, Luger—who is also a  (HHMI) Investigator— on the genomic structure of microbes called Archaea, findings that hinted at the evolutionary origins of DNA folding that all multicellular organisms use. The research built on Luger's cornerstone scientific achievement, which outlined the three-dimensional structure of the nucleosome. That finding, now widely cited in textbooks, was named the â€śbreakthrough of the year” in 1997 by the journal Science.

Ahn joined the CU Â鶹ӰԺ faculty in 1992 and served as an HHMI Investigator from 1994–2014. She serves as President of the American Society of Biochemistry and Molecular Biology. 

“This is such a great honor," said Ahn, a Professor of Distinction in Chemistry and Biochemistry and Associate Director of the BioFrontiers Institute. "I owe many thanks to my past mentors, and to my wonderful colleagues, students and friends in our amazing CU Â鶹ӰԺ community.”

Ahn's research focuses on enzymatic and cellular mechanisms underlying cell signal transduction. She conducted pioneering work in the discovery of the mitogen-activated protein (MAP) kinase cascade, including the identification of MAP kinase kinases which are important targets for anti-cancer therapies. She was also a pioneer in the use of functional proteomics and mass spectrometry for signal transduction research.

The 2018 class of National Academy of Sciences inductees includes 84 researchers from across the country as well as 21 foreign associates. The new inductees bring the total number of active members to 2,382 and the total number of foreign associates to 484.

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