Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

GenSAT (Gene Expression Nervous System Atlas) project announced

30.10.2003


Unprecedented genetic access to brain provided by Rockefeller University scientists



For scientists studying the brain, this week’s Nature announces a remarkable new map describing previously uncharted territory, plus the means of exploring the new horizons for themselves. Rockefeller University scientists led by Nat Heintz, Ph.D., and Mary Beth Hatten, Ph.D., are well under way on a genetic atlas of the mammalian brain that provides unprecedented access to central nervous system regions, cell classes and pathways.
"Researchers studying degenerative and developmental diseases from Parkinson’s and Huntington’s to autism and epilepsy now will have genetic access to the brain without all the effort required of doing their own molecular genetics from scratch," says Heintz. "Gensat will advance the experimentation that can be done based on the information provided in the atlas; to me this is the key contribution of our project."

The project, called Gensat (Gene Expression Nervous System Atlas) employs a method for manipulation of "bacterial artificial chromosomes" or BACs, developed by project co-leader Heintz, professor and head of the Laboratory of Molecular Biology at Rockefeller and an investigator at the Howard Hughes Medical Institute. BACs in an early form provided the backbone of The Human Genome Project; Heintz discovered how to manipulate them by inserting, changing or deleting parts of the large gene sequences composing them. Once created, the modified BACs for individual genes are inserted into the genome of laboratory mice to assess gene expression.



The BAC technology provides unparalleled insight because it identifies the actual cell types in the brain in which individual genes express themselves. Heintz also added a reporter gene to the BACs so that cells with the selected gene activity glow bright green. Many new brain cell types or subtypes have been discovered in this project as a result of the potent tool. (Traditional methods of genetic analysis such as in situ hybridization cannot distinguish among cell types for gene expression, and therefore are not as powerful.)

Gensat comes with the accoutrements necessary for scientists anywhere to further improve our knowledge of the brain and its diseases. Gensat is a fully public, searchable database of gene expression in all central nervous system cell types for individual genes. What’s more, Gensat provides the tools (BAC vectors and transgenic mice) used in the project for researchers interested in following up on new disease-based insights revealed in the atlas. One hundred-fifty genes are analyzed in the new database at www.gensat.org, with 100 more genes scheduled for posting soon.

"We are providing more information in our database than has ever been known in the central nervous system," says Hatten, professor and head of the Laboratory of Developmental Neurobiology at Rockefeller. "There isn’t a single gene among the 150 currently on our public atlas that has been studied in the range of detail that we have provided. If biologists tend to explore things locally in great detail, we’ve started examining a global economy of the central nervous system."

Gensat analyzes up to five genes per week in a high-throughput laboratory space provided by The Rockefeller University. Heintz and Hatten plan to analyze gene expression in all central nervous system cell types for 250 to 300 genes per year.

Landmarks in the brain

Maps are valuable when they exhibit distinguishing features of the landscape. The same is true for Gensat. When the two Rockefeller scientists conceived the project four years ago, Hatten knew she would need to put her considerable expertise in imaging the brain to work if Gensat was going to succeed. Today, the Gensat project recreates for scientists and students the experience of sitting down to look at brain specimens at a microscope. Seeing genes expressed in every cell type in the brain, and viewing that expression in a traditional, anatomical format, provide researchers with more insights about the function of genes.

To achieve this result, the project’s automated microscope records mouse brain specimens for every gene in the atlas at three developmental stages. The images are captured at high resolution, checked for accuracy by several of the 20 researchers involved with the project, annotated and prepared for inclusion in the database.

The organizational challenge alone for such a large-scale project is impressive. But Heintz and Hatten faced more than an organizational challenge when they started out. The means of displaying high-resolution digital images on the scale they envisioned simply did not exist.

"It was like going into a bike shop and designing a bike that no one has ever imagined before," says Hatten. "All the components were available, but we had to put them together and design the computing systems to run them for the first time."

The lead duo were fortunate to attract gifted scientists and a programmer to the project, without whom, they would never have achieved all the significant technical infrastructure and refinements required at every stage. The scientists include Shiaoching Gong, Chen Zheng, Martin Doughty, Kasia Losos and programmer Nick Didkovsky. Heintz and Hatten describe this group as "some of the most talented young researchers we’ve ever worked with." Remarkably, Didkovsky, without prior exposure to science, worked closely with Hatten to build an operating system for Gensat from the ground up.

This year, Gensat has received multi-year funding from the NIH’s National Institute of Neurological Disorders and Stroke. But in the three years that it took to refine the imaging, computing system and BAC methodology as well as set up the large-scale mouse transgenic operation that powers the project, Hatten and Heintz have relied on The Rockefeller University’s tradition of supporting researchers undertaking risky, but potentially important science.

"Without the university, this project simply would not exist," says Hatten. "Rockefeller has made it all work out; they’ve funded all computer systems, a full-time software programmer, as well as built us lab space for the researchers working together on this project."

"A lot of scientists form companies," says Heintz. "We thought about that, too, but we didn’t want to see so much valuable information and the tools we created reserved for scientists with big resources to buy database information, vectors and transgenic mice for their experiments." The university and NIH have helped fulfill Heintz and Hatten’s goal of keeping this project truly public.


###

Lynn Love | EurekAlert!
Further information:
http://www.rockefeller.edu/

More articles from Life Sciences:

nachricht World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>