Introducing Karolin Luger- Finding Her Way through Chromatin

bridges vol. 14, July 2007 / News from the Network: Austrian Researchers Abroad

by Elisabeth Hartlieb



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Prof. Karolin Luger

"Figuring out how things work has always been my passion," explains Karolin Luger, a Howard Hughes Medical Investigator and Monfort Professor at Colorado State University. Very likely this natural curiosity is one of the big factors in Luger's formula for success. While a research assistant professor at the Swiss Federal Institute of Technology in Zurich (Eidgenössische Technische Hochschule Zürich, ETH Zürich) she solved the structure of the nucleosome, a major breakthrough in the scientific community that is now cited in every modern textbook of molecular biology.

→ A Chromosome is a single large macromolecule of DNA. Only during nuclear division do chromosomes have the typical X shape in which they are most commonly portrayed. The two arms are called Chromatids, each of which consists of two strands of DNA. Chromatids are joined at the Centromere and consist of Chromatin, a complex of DNA and proteins that makes up the chromosome.

What's happening inside a cell can be compared to an old-fashioned music tape and a cassette player. The genetic information is stored in the DNA, much as music is encoded in a linear way on the magnetic tape. In order to listen to the music, it must be decoded back to sounds. A lot of music can be stored on one tape, and that one tape must be rather small to fit into the tape player; hence, the encoded music must somehow be compressed. This process of packing and unpacking is quite similar to what occurs in human DNA, which stores information on "how and what kind of human to build." However, the nucleus, the place where the DNA is stored, is exceedingly small. Luger's main area of research focuses on how the DNA is physically packaged in the cell's nucleus, and how this packaging affects "which type of music you are listening at any given time," as she explains.


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Digging deep: a quick brush-up on cell biology basics


To understand the nucleosome, which is the fundamental packing unit of the human genome, we must dig deep into a cell. Remember biology class at school: inside a human cell's nucleus are 23 pairs of chromosomes. Each of these chromosomes contains a long double-stranded DNA molecule that holds genetic information, part of the so-called human genome.

 

 

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The DNS in the nucleus is packed together in hierarchical structures with proteins



The DNA is combined with proteins into a complex referred to as chromatin, whose structure controls whether the cell can transcribe genes and replicate and repair DNA. And that is when Dr. Luger enters the scene:

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The nucleosome is representing the fundamental packaging unit in the human genome

Dr. Karolin Luger, one of the world's foremost authorities on nucleosome structure, has dedicated her work to researching the structure of chromatin and its effects on the flow of information. Remember, it is the nucleosome that functions as the fundamental packaging unit of chromatin. The picture on the right shows a nucleosome; different types of proteins are displayed in green, yellow, red, and blue, whereas the DNA is displayed in white. Luger made this discovery at a time when scientists thought there wasn't much more to explore inside a cell, so her work laid the foundation for her current research activities.


Entering the "Luger Lab"

"... basic research knowledge simply has to be accumulated for the sake of it, as you never know what might come out of it..." [Karolin Luger]


At the Luger Lab about 20 researchers are working simultaneously on six or seven projects. Professor Luger established her lab in 1999 with two postdocs and one graduate student. Since then, it has experienced significant growth due to a vigorous and smart grant application policy. Their latest big success was discovering how the Kaposi's sarcoma-associated herpes virus (KSHV), which has a causative role in a cancer associated with HIV infection, gets inside a cell. Apparently, it does so by "hitchhiking." A viral protein recognizes the surface of a nucleosome and soon is annexing the viral DNA, like a stowaway, on the human chromosome. These findings have been important for better understanding how the herpes virus, associated with Kaposi's sarcoma, endures in the multiplying cells of a growing tumor (to learn more about KSHV, please click here).

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Luger's Lab is located on the third floor of the Molecular and Radiological Building

Generally speaking, Luger and her lab deal with epigenetics, commonly defined as the study of heritable changes in gene function that occur without a change in the DNA sequence. For a practical example of her work and the impacts it has on other things, Luger refers to the famous sheep, Dolly. "When you do a clone, when you clone Dolly the sheep, it does not look the same as its mother. And that is because it's epigenetic. Its DNA is exactly the same, there is no question about it, but the modification of the DNA is different. And so that's an example of epigenetics which is really our field of research."


From dream to reality


Back in 1999, while Luger was sitting on the yet-to-be-unpacked moving boxes in her lab, she already felt that "this is going to work." Her intuition proved to be right, when she received the Searle Scholar Award, a scholarship which is granted to only 15 persons in the US each year. It was an important start-up support for her research work and was followed by the Basil O'Conner Starter Scholar Research Award, the highly distinguished Monfort Professor Award, the nomination to be a Howard Hughes Medical Institute Investigator, and finally by her promotion to University Distinguished Professor last year.

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High-rope-course, Labtrip 2006

One can sense the family-like atmosphere in the lab, when Luger starts talking passionately about her staff. She praises her team for their talent and independent working style and the very high standards they are setting for themselves, which in turn are attracting new overachievers to the Luger lab. The different teams, although working on independent projects, benefit each other. Synergistic effects occur along with cross-fertilization of the different research areas. Researchers share their expertise, research facilities and, last but not least, they all take advantage of the excellent infrastructure provided by the lab.

Luger deeply appreciates the highly supportive environment at Colorado State University. When the university offered her the position as professor, Luger says she intuitively knew that Colorado State was the right place for her. Since then she has never regretted her decision, even if other places might have had a better reputation. For Luger it was the high potential, the enthusiasm for her coming, and the people there that really counted and make working at Colorado State so enjoyable for her.


Hands-on science


When Luger is asked what she wants to achieve with the current research in her lab, she smiles whimsically. Although admitting that she has some big dreams that she would like to accomplish, she rather prefers not to talk about them right now. And who could blame her for that? It would be like giving free hints to others about what to concentrate on. Nevertheless Luger revealed that some of the present lab work consists of projects like the previously mentioned research on how the virus causing Kaposi's sarcoma survives inside a cell without being killed by the cell's defense mechanism.

Her current research also includes other types of the more-than-500 different kinds of cancers. Besides cancer research, the lab is currently investigating a severe form of a hereditary disease that primarily affects girls and causes mental retardation. Obviously the research field of epigenetics is becoming more and more popular with the discovery of further diseases related to it. Based on the existing achievements, further explorations in epigenetics are sparking the hope of finding cures for some of these diseases.

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"It´s one of the hallmarks of civilization to do research."

Luger sees the future of science in collaboration between different institutions as well as on an interdisciplinary level. Among many other collaborations, her lab has intense cooperation with other researchers from Colorado State University as well as international research cooperations like the one with David Tremethick from the Australian National University . At the same time, Luger points out that research partners have to be chosen carefully because science is a very competitive field. But usually, collaboration goes smoothly and both parties enjoy mutual benefits. Luger recalls that, more than once, a true friendship has developed from a research cooperation, and liaisons continue even after the grants for the projects have run out.

Due to time constraints, Luger's active time at the lab bench is over. Now she sees her "scientist" role as the facilitator for the research her staff is conducting. Luger keeps the big picture in mind and guides her staff. She spends most of her days writing grants and papers, doing administrative work, reading papers, talking to their collaborators, teaching, and mentoring her students and lab team members. Of course there is always some trouble-shooting necessary in the lab. Most of her lab time is spent talking with people in the lab about their research, as well as their personal concerns.


It's all the same, isn't it?

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The Luger Lab

When asked about the differences in the Austrian and American ways of research, Luger points out that in America a lab is run more like a business, which makes a substantial difference when it comes down to financing. But above all, the general concept of research is more positive in the US than in Europe, which makes working in the US more pleasant.

When thinking back to her research time in Austria, bureaucracy was a major challenge because, "if you need a piece of equipment you need it right now and not in three years," Luger says, and hence an unbureaucratic way of handling things is necessary. Besides, Luger isn't very fond of the hierarchical habilitation system that is still active in Austria. In her opinion, it constrains researchers during the most creative time of their careers. Although Luger has not worked in Austria that much as a researcher, she hears from her colleagues back home that getting funding is too complicated. Nevertheless, she points out that much has been achieved in the European field of epigenetics at institutions such as the Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA) in Vienna, or the Max Planck Institute in Germany.

Going back home - at least for a day

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Dr. Luger accepting the honor from the Governor of Vorarlberg Dr. Sausgruber

Luger's research is internationally recognized and appreciated, but it was a special moment for her when she received the Würdigungspreis des Landes Vorarlberg für Wissenschaften (an award for outstanding scientific achievements, granted by the Austrian federal state of Vorarlberg) in April 2007. Having lived in the US for eight years, Luger was surprised that people in Austria still think about her, and she was highly honored to receive the award. Traveling to Europe was a great opportunity for her to have a family reunion. As an additional "bonus," Wolfgang Rümmele, her former biology teacher from school and now the mayor of her hometown of Dornbirn, presented the award to her.

When Luger accepted the position as a professor at Colorado State University, she knew that this would probably imply a permanent move to the States. Although she misses much about Austria, like the beautiful scenery, the mountains, the lakes, the sound of the cowbells . . . she really enjoys living in the States. For her, living in the US is easy and laid-back. Still, she tries to go back to Austria at least once a year, mostly in connection with a work trip. For Luger it's important that her three-year-old daughter gets "some grandparents time" in Austria, and that she can meet her family and friends there.


A role model's perspectives

Luger is a strong believer in role models, partly because she wished she'd had one herself when she was younger. The more she advances in her career, the more important it is for Prof. Luger to serve as a role model herself for young female scientists and to generally show people there's something in science that can be done, and it's possible to do it.

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Luger's research associate Dr. Uma Muthurajan at work

"It's one of the hallmarks of civilization to do research," Luger points out. Hence it's very important for even high school students to realize the possible benefits of science and research. Talking about "new blood" in the field of Molecular Biology, Luger says there has been a slump in the so-called .com area. For a while, it was hard to find and get really good people, because big money was made in the IT field and everybody wanted to work there. Nowadays, there are once again many young researchers interested in the field of molecular biology. More and more scientific breakthroughs and practical applications are attracting highly qualified people to this research field. So now, more often than not, she has to turn down highly qualified people because there are not enough human or financial resources to support them.

Family life and a career are certainly possible simultaneously, but it takes an understanding partner, excellent time management and, last but not least, the willingness of all involved parties. Clearly Luger does not have much time for hobbies, but what she would really like to do and what she misses most is playing the piano. This explains her answer to the question: With what random person would you like to have lunch? Her answer: Alfred Brendl, a pianist who is supposed to be among the greatest musicians of the 20th and 21st centuries.

Speaking of the 21st century, Luger believes that one of the greatest scientific challenges for this century, with a desperate need for action, is global warming. According to Luger, the US is 20 years behind Europe in terms of energy savings and public awareness, but a gradual shift is slowly occurring in the people's mind-set. The biggest biological science challenge for Luger would be to decipher the working of the human brain. This, she adds, might be a contradiction in itself as the human brain would need to understand itself . . . But never say never - to someone who has deciphered the structure of the nucleosome, even the human brain may be another fascinating mystery just waiting to be solved.


References:

· http://welcome.colostate.edu/

· http://www.ethz.ch/index_EN

· http://lugerlab.bmb.colostate.edu/Start.htm

· http://en.wikipedia.org/wiki/Kaposi's_sarcoma-associated_herpesvirus

· http://www.searlescholars.net

· http://www.marchofdimes.com/professionals/691_14437.asp

· http://www.imba.oeaw.ac.at/

· http://www.eva.mpg.de/

· http://www.hhmi.org/

· http://lugerlab.bmb.colostate.edu/StaffCurrent.html

· http://www.hhmi.org/news/luger20060209.html

· http://www.genome.gov//Pages/Hyperion//DIR/VIP/Glossary/Illustration/chromosome.cfm

· http://www.srtp.org.uk/germclon.htm (info about germline therapy)

· http://en.wikipedia.org/wiki/Epigenetics

· www.vorarlberg.at/Landtag/

· http://www.vp-dornbirn.at/ruemmele.html

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The author Elisabeth Hartlieb is a student at the Innsbruck University School of Management.
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