Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Vollum Institute discovery may unlock human genome

29.12.2004


An Oregon Health & Science University-led development of a technique for identifying control elements that drive the expression of genes in brain cells could unleash the disease-fighting potential of the much-hailed human genome.



Scientists at the OHSU Vollum Institute, which headed the multidisciplinary study appearing in the Dec. 29 edition of the journal Cell, are calling the approach a significant advance in understanding the genome. The Vollum’s director, Richard Goodman, M.D., Ph.D., professor of cell and developmental biology, and biochemistry and molecular biology, OHSU School of Medicine, said the technique could give a critical boost to the new era of genomic discovery set forth when the Human Genome Project was completed early last year. "The question was how to understand the enormous amount of genomic information that has been generated," Goodman said. "Our approach will help unlock the regulatory control of the genome." The approach could heighten understanding of the pathways behind genetic aberrations that cause diabetes, Parkinson’s disease, heart disease, cancer and other diseases, he said.

The Vollum team’s technique, developed in collaboration with scientists at Brookhaven National Laboratory in Upton, N.Y., and State University of New York, Stony Brook, resulted from an effort by Soren Impey, Ph.D., in Goodman’s laboratory to characterize a family of genes regulated by the "cAMP response element binding" protein, or CREB. This well-characterized molecule is among a group of proteins called transcription factors that interact with regulatory elements in DNA that are responsible for increasing or decreasing the level of gene expression in cells.


The technique involves linking DNA from a cell with the transcription factor protein, then isolating the complex through a process called immunoprecipitation. Strips of 21-nucleotide-long DNA are then released from the immunoprecipitated DNA to create "genomic signature tags," which are then identified in the international genome database. The method uncovered about 6,300 regulatory regions that mapped to distinct sites on the genome. "A subset of these regions highlight novel genes," said Impey, assistant professor of neurology, OHSU School of Medicine, and the study’s lead author.

Goodman calls the process "the most comprehensive analysis to date in a metazoan system – that is, a multicellular system – of where transcription factors bind to their genomic targets." It gives scientists a system for mining the entire genome for all the regulatory sites involving a given transcription factor protein. "You can start to put together a transcriptional map of pathways that are involved in cellular function," he said. "In the past, it’s only been possible to look at a very small part of the genome, but now we can look at the whole thing. It’s a big step forward."

David Ginty, Ph.D., professor of neuroscience at The Johns Hopkins University School of Medicine in Baltimore, studies molecular control of growth and survival of neurons in the developing vertebrate nervous system as a Howard Hughes Medical Institute investigator. He said the challenge to exploiting the human genome has been to uncover the relationships between identified genes and to understand how complex patterns of gene expression take place.

But the Goodman lab’s discovery, Ginty said, will help scientists understand how transcription factors coordinate complex genetic patterns and, therefore, how different cells are made and how they function. "The study establishes a beautifully simple approach to identifying mechanisms of complex genomic control," he said. "The method should prove useful for establishing how sets of genes are turned on or off in any given cell type, and how cellular and functional diversity is achieved."

Exploration of the humane genome has been frenzied since the International Human Genome Sequencing Consortium, led in the United States by the National Human Genome Research Institute and the Department of Energy, and The Institute for Genomic Research (TIGR), a private genome sequencing company, announced the completion of the Human Genome Project more than two years ahead of schedule in April 2003. Between 20,000 and 25,000 genes coding for proteins that perform most life functions were found. But there was a problem.

"That’s not very many genes," Goodman said. "And so, in a sense, declaring the genome solved was somewhat arbitrary because it’s solved when you really understand it. If you look at the genome, or the database that the genome provided, what you have is a bunch of letters and it has to be decoded to understand what those letters mean."

Goodman compared the genome to a phone book in which the names were interspersed "with a lot of nonsense letters," and the names themselves were broken into pieces. "And rather than having 26 letters, there are only four, and they’re all mixed up," he said. "It’s hard to know where the genes start and stop."

Said Impey: "Although the Human Genome Project identified about 25,000 protein-coding genes, the instruction set that regulates these genes is, for the most part, unknown. This is important because what makes a cancerous cell different from a noncancerous cell is the set of genes that are turned on or off. These instructions or regulatory regions are believed to be far more numerous than genes, but it was not clear how to identify them." "We developed a novel technique that is able to isolate a comprehensive set of regulatory regions and map them to the entire genome. Our work will help unravel the genomic instruction set that governs how genes are regulated in a given cell type. If one views the genome as a multidimensional puzzle, our method helps make the puzzle a little simpler."

The discovery already has demonstrated its implications for human diseases. Goodman’s lab is working with the OHSU Cancer Institute on a cancer-causing oncogene that arises when a rearrangement of chromosomes generates an abnormal transcription factor. "If you had a technique that would allow you to take that factor and identify what its targets are, you would understand why that oncogene causes cancer," Goodman said.

Another project is examining a transcription factor involved in the differentiation of dopamine-producing cells. By identifying the targets of the transcription factor, stem cells differentiated as dopamine cells could be developed to treat Parkinson’s disease.

And a project with Markus Grompe, M.D., of the OHSU Oregon Stem Cell Center is studying the transcription factor involved in pancreatic beta cell differentiation. "This is a factor that drives the expression of insulin, but also other differentiated properties of a beta cell, so if we can identify all those targets, we’ll understand something about the nature of the development of a beta cell," Goodman said.

Ginty, of The Johns Hopkins University, said the future could even hold answers to such questions as how a neuron in the brain stores information that forms the basis of memory. "The future of genome exploration will bring an understanding of how the genome is controlled to yield different cell types of the body and their various functions," he said.

In addition to Goodman and Impey, study collaborators included: Hyunjoo Cha-Molstad, Jami Dwyer and Gregory Yochum, Vollum Institute; Sean McCorkle and John Dunn, Brookhaven National Laboratory; Jeremy Boss, Emery School of Medicine; Shannon McWeeney, OHSU; and Gail Mandel, State University of New York, Stony Brook.

: Jonathan Modie | EurekAlert!
Further information:
http://www.ohsu.edu

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Silicon solar cell of ISFH yields 25% efficiency with passivating POLO contacts

08.12.2016 | Power and Electrical Engineering

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>