Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene design program from Johns Hopkins simplifies, automates and speeds design of ’artificial’ genes

16.02.2006


Johns Hopkins researchers have announced the development of a Web-based, automated computer program that they say greatly simplifies the time-consuming and error-prone process of manually designing artificial pieces of DNA.



The program, called GeneDesign, guides the design of blueprints for DNA segments to the exacting specifications required for studying gene function and genetically engineering cells. The blueprints are then used by companies or other investigators to synthesize the gene.

A report on the program appears in the April 2006 issue of Genome Research and online in mid-February. The publicly accessible Web site can be found at http://slam.bs.jhmi.edu/gd.


GeneDesign automates the process of determining which base pairs -- the building blocks of DNA -- should be linked together in a particular order to make a gene, according to Jef Boeke, Ph.D., professor of molecular biology and genetics and director of the High Throughput Biology Center at The Johns Hopkins University School of Medicine. A gene codes for a specific protein, and the order of the hundreds or thousands of base pairs making up that gene determines the order of the amino acid building blocks making up that protein. Boeke is senior author of the paper.

"GeneDesign not only guides the user in designing the gene, but also automatically diagnoses design flaws in the sequence of bases making up the gene," said Boeke.

Simplifying creation of so-called designer or artificial genes is important because slight changes in the choice of base pairs making up specific parts of the gene can have significant effects on how the gene works and how efficiently it can be inserted into cells. "In the past," said Boeke, "researchers had to use many different programs to address all the requirements of the separate steps of synthetic gene design."

The researchers have so far used GeneDesign to make a variety of synthetic sequences, including a Ty1 element -- a mobile piece of genetic material found in yeast cells. Ty1 elements can move from one yeast cell and "jump" into a specific spot in one of a second yeast’s chromosomes. This jumping movement can cause mutations or bring in additional genetic material to the yeast.

GeneDesign consists of six modules that can be used individually or in series to automate the tasks required to design and manipulate synthetic DNA sequences. The program allows the user to start with either the sequence of the amino acid making up the protein or the bases making up the gene that codes for that protein. Then the user moves through a series of steps that guide the design of the gene and vector that will carry the gene into the cell. Users can follow the main "Design a Gene" path or use the modules individually as needed. Vectors are mobile pieces of DNA that are used to carry artificial genes into cells.

A major advantage to GeneDesign is the ability to choose specific codons that work especially well in specific organisms, Boeke said. A codon is a trio of bases in a gene that codes for a specific amino acid building block. Most amino acids are represented by more than one codon. For example, the codons GCU, GCC, GCA, GCG can each code for the amino acid alanine.

Human, bacterial and yeast cells often differ in the codon they prefer to use for a particular amino acid. "GeneDesign automatically chooses the best codon to use depending on whether the gene is supposed to work in a human cell, a bacterium, or a yeast cell," Boeke said. "When you’re working with hundreds of codons, that’s a significant help."

The program also simplifies the design of genes that will make proteins with desired, specific modifications -- for example, changes that make them work more efficiently.

Another advantage of the GeneDesign is ease of creating restriction sites -- places along the DNA where the gene can be cut, said Sarah M. Richardson, a Ph.D. candidate in the Department of Genetic Medicine at Hopkins and first author of the paper. Scientists use molecular scissors called restriction enzymes to make these cuts, which allow them to do the cutting and pasting needed to put artificial genes into vectors.

"GeneDesign guides the choice of the series of base pairs where the restriction enzymes cut the DNA," Richardson said. "That lets investigators use different restriction enzymes to make cuts exactly where they want to."

If the same restriction site sequence occurred throughout the gene, the specific restriction enzyme that recognizes that site would make multiple cuts, according to Richardson. "That would make it impossible to do the precise cutting and pasting needed to make and use artificial genes," she said.

However, even a successfully designed gene would not benefit researchers if there were only one copy of it. "To make use of artificial genes we need to make millions of copies of them for experiments using a process called polymerase chain reaction," said Boeke. "By putting restriction sites into specific spots along the gene, we can cut it into bite-sized pieces that are easily duplicated millions of times. So the ability to cut and paste genes back together again is critical for designing genes to the right specifications, rapidly replicating them and putting them into vectors to genetically engineer cells."

The other authors of the paper include Sarah J. Wheelan and Robert M. Yarrington of The Johns Hopkins University School of Medicine High Throughput Biology Center.

Eric Vohr | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/mediaII/RSSinstructions.html
http://slam.bs.jhmi.edu/gd

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice 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: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>