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 Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>