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LSI Today: Pushing the Boundaries of Big Science

Nearly a decade ago, former U-M President Lee Bollinger charged a blue-ribbon commission to study the University's response to the transformational change in science marked by the mapping of the human genome.

"We seem to be entering an era of significant exploration of life," Bollinger explained. "The University must be prepared to participate fully and preeminently in the exploration of this extraordinary advance of knowledge."

The most visible result of that effort was the creation of the Life Sciences Institute (LSI) linking the medical campus with central campus in both physical and intellectual dimensions. Completed in September of 2003, LSI has transformed from a state-of-the-art laboratory without walls into a hub of collaborative, multi-disciplinary life sciences research. It has recruited 25 faculty members and has about 500 people working in the building including over 100 undergrad and graduate students.

With the leadership of President Mary Sue Coleman and LSI Director Alan Saltiel, an active advisory board, leadership council, faculty and staff, the accomplishments are significant.

"Michigan has leading researchers working together toward a richer understanding of life on every level, and the Life Sciences Institute is the perfect model for pushing boundaries and building knowledge," said President Mary Sue Coleman. "The assets the Institute brings to fruition—new research, new curriculum, new faculty, and the new building and facilities—are examples of the University's commitment to excellence across the life sciences."

Within LSI, outstanding scientists from a variety of disciplines including physiology, cell and molecular biology, chemistry and biological chemistry, genetics, bioinformatics and structural biology, are focusing on the biological problems of human health in interdisciplinary teams. LSI faculty work on cancer, diabetes, cardiac and circulatory disease, and neurodegenerative and infectious disease.

"The dynamic environment we have created directly results from the people working here," said Alan Saltiel, director. "We have recruited the best scientists, supported them well, and created an intellectual environment that allows ideas to accelerate."

The collaborations and research have proved fruitful, spanning across physical floors and lab benches, and disciplines. Many of these research efforts have produced important breakthroughs including:

• Janet Smith and David Sherman worked together to discover how enzymes generate the large rings in antibiotics that make them work.
• Kun-Liang Guan and Sean Morrison revealed new indications for the cancer drug rapamycin.
• Anuj Kumar and Jason Gestwicki devised chemical manipulation of protein location.
• Patrick Hu and John Tesmer studied structures of novel genes in the insulin/IGF-1 pathway.
• Alan Saltiel and Steve Weiss looked at the role of the extracellular matrix in fat development and expansion.
• Jiandie Lin discovered the central regulator connecting the biological clock and metabolism.

The Institute has created crossroads for all U-M faculty and students to engage across fields and other academic boundaries through the Institute's three centers in chemical genomics, structural biology and stem cell biology. Each of these collaboratories has already achieved significant milestones:

• The Center for Chemical Genomics has completed over 20 screens and has received a $1.5M grant for supporting pilot projects in screening technology.
• The UM Center for Stem Cell Biology has recruited 2 outstanding junior faculty to work with director Sean Morrison and has developed an important project on human embryonic stem cells with donor support.
• The Center for Structural Biology has established capacities and technology in high throughput protein production and high through-put crystallization resulting in the 37 new structures solved since the Institute opened.

LSI faculty have been instrumental in creating new networks on campus including: improving science teaching with Dan Klionsky's "active learning" approach; Shawn Xu's and Patrick Hu's U-M working worm group; and sci/art connection program between LSI, the School of Art & Design, and U-M Museum of Art.

"As research has evolved with scientific discovery, LSI has changed with it, both in depth of field and breadth of research and support," said LSI Managing Director Liz Barry. "We are continuing to build upon the strengths and explore the frontiers of sciences at U-M and are proud of our accomplishments and promise, not only in discoveries, but in reaching out to the life sciences community."

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Strong Support for Stem Cell Research

The Life Sciences Institute raised almost $400,000 in private funds to support a project on human embryonic stem cell research currently not eligible for federal funding. The project is part of the U-M Center for Stem Cell Biology, which was launched in 2005 with $12M in start-up funding from U-M.

"On the day President Bush vetoed the legislation in late July, I asked a group of the Institute’s stakeholders to help us stay leaders in the field by funding this critical area of research until the federal restrictions are eased. The response was positive and immediate," said Alan Saltiel, director of the Life Sciences Institute.

In the past eight months, the Institute raised $383,600 with a goal to raise a total of $1.25M to fund the project for four years. The donors include current and former U-M regents and many local and national leaders who believe this research is vital to find cures to the most devastating diseases.

"Our funders are representative of the majority of the public who are in favor of embryonic stem cell research; it offers the best hope to speed the pace of discovery for treatments and cures for diseases like diabetes, Parkinson’s and cancer," Saltiel said.

There was broad bipartisan support for the Castle-Degette legislation that Bush vetoed in July and which would have allowed federal support for research on newly-derived human embryonic stem cell lines. Currently, federal funds may only be used to fund stem cell research using the few stem cell lines that were in existence when President Bush entered an executive order in 2001.

Michigan state law prohibits researchers from creating new stem cell lines by destroying human embryos within the state and from genetically tailoring stem cell lines for use in specific patients through a process called "nuclear transfer."

"I committed my support within hours of Dr. Saltiel’s request," said Ernest G. Ludy, founder and former CEO of Medstat (now Thomson Medstat), headquartered in Ann Arbor. "This research is too important to be halted by overly restrictive state and federal policies."

"The University has a track record of success in stem cell research and my wife Kathy and I believe it is absolutely vital that Michigan continues to lead during this period. We were pleased to be able to support research that may some day lead to cures for the terrible diseases that have touched all of our lives," said Phil Power, former U-M Regent and founder and former owner of Hometown Communications, a publisher of local and regional newspapers.

The Director of the U-M Center for Stem Biology, Sean Morrison, is developing the research plans for the project, which is now getting underway. A room in LSI has been established and equipped for work on embryonic stem cell lines entirely with private donor money. This room may be used by any scientist at the University of Michigan who wishes to pursue research projects that depend on the use of newer embryonic stem cell lines that are not approved for NIH support.

"With these private funds, we will be able to work on newer human embryonic stem cell lines that have been created since 2001. These newer lines are better because they are uncontaminated by animal products and will allow us to model inherited human diseases," said Morrison.

"We are already at a disadvantage in Michigan because of our state law restrictions. That makes this support even more critical for our Center. In the areas where Michigan can conduct stem cell research, we have been recognized as among the best institutions internationally," Morrison said. "It is important to remember that these restrictions under Michigan law do not protect a single embryo from destruction; they only delay medical research."

The U-M Center for Stem Cell Biology was created a year ago with joint funding by the U-M’ s Medical School, Strong Support for Stem Cell Research Cancer Center, Molecular and Behavioral Neuroscience Institute and the LSI.

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In Memoriam: Martha Ludwig, PhD

MARTHA LUDWIG, Ph. D.

Martha Ludwig, Ph. D., prominent University of Michigan scientist, died on November 27, 2006. Since her arrival to the University of Michigan faculty in 1967 as an Assistant Professor, Dr. Ludwig was always an active and important part of the scientific community at the University. She was the J. Lawrence Oncley University Professor of Biological Chemistry at the University of Michigan Medical School and also Senior Research Professor in the Biophysics Research Division. Dr. Ludwig served as the Chair of the Biophysics Research Division from 1986-89 and initiated the Molecular Biophysics Training Program at the University of Michigan. She also played a major part in the development of the Michigan Life Science Corridor-funded synchrotron beam line.

At the University of Michigan, Dr. Ludwig has been recognized for her scholarship, her many leadership activities and also for her thorough training and mentoring of graduate students. According to her former students, she involved them in frequent and intensive brainstorming sessions to analyze data and plan future experiments, and also gave them many opportunities to meet and "talk shop" with other renowned scientists.

Outside of the University of Michigan, Dr. Ludwig has been recognized throughout the U.S. and internationally for her studies of proteins using X-ray crystallography. Her specialty was the structure and function of enzymes that employ the vitamins riboflavin and B12 as cofactors. She also solved the first structure of a flavin-containing protein.

Her many scientific achievements have been recognized by the Garvan Medal of the American Chemical Society in 1984, by the Distinguished Faculty Achievement Award from the University of Michigan in 1986, by election as a Fellow of the American Association for the Advancement of Science in 2001, and by election to the U.S. National Academy of Science in 2003, and most recently to the Institute of Medicine in 2006.

Dr. Ludwig was born in Pittsburgh in 1931. She obtained her undergraduate degree in chemistry at Cornell University in 1952, her Masters’ in chemistry from the University of California at Berkeley in 1955, and her Ph. D. in biochemistry at Cornell Medical College in 1956. She also held postdoctoral positions at Harvard and MIT.

Dr. Ludwig is survived by her husband of 45 years, Frederic Hoch, who was Professor of Internal Medicine and Biological Chemistry until retirement. Together they enjoyed hiking, skiing and bird-watching.

Dr. Ludwig was a valued colleague and friend and a distinguished figure at the University of Michigan and in the international scientific community, and she will be dearly missed.

Gifts in memory of Dr. Ludwig can be directed to the Martha L. Ludwig Memorial Fund at the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606. Checks should be made out to the University of Michigan.

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