Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

A Digital Test for Toxic Genes

Published: Thursday, January 30, 2014
Last Updated: Friday, January 31, 2014
Bookmark and Share
TAU researchers develop a computer algorithm that identifies genes whose activation is lethal to bacteria.

Like little factories, cells metabolize raw materials and convert them into chemical compounds. Biotechnologists take advantage of this ability, using microorganisms to produce pharmaceuticals and biofuels. To boost output to an industrial scale and create new types of chemicals, biotechnologists manipulate the microorganisms' natural metabolism, often by "overexpressing" certain genes in the cell. But such metabolic engineering is hampered by the fact that many genes become toxic to the cell when overexpressed.

Now, Allon Wagner, Uri Gophna, and Eytan Ruppin of Tel Aviv University'sBlavatnik School of Computer Science and Department of Molecular Microbiology and Biotechnology, along with researchers at the Weizmann Institute of Science, have developed a computer algorithm that predicts which metabolic genes are lethal to cells when overexpressed. The findings, published in Proceedings of the National Academy of Sciences, could help guide metabolic engineering to produce new chemicals in more cost-effective ways.

"In the lab, biotechnologists often determine which genes can be overexpressed using trial and error," said Wagner. "We can save them a lot of time and money by ruling out certain possibilities and highlighting other, more promising ones."

Gaining an EDGE
When metabolic genes are expressed, the genetic information they contain is converted into proteins, which catalyze the chemical reactions necessary for life. Overexpression means that greater-than-normal amounts of proteins are produced. Biotechnologists typically overexpress native genes of an industrial microorganism to boost a certain metabolic pathway in the cell, thus increasing the production of desired compounds. Sometimes they overexpress foreign genes — genes transferred from other organisms — in an industrial microbe to build new metabolic pathways and allow it to synthesize new compounds. But they often find that their efforts are hindered by the toxicity of the genes that they wish to overexpress.

Prof. Ruppin's laboratory builds large-scale software models of cellular metabolism, one of the most fundamental aspects of life. These models convert physical, chemical, and biological information into a set of mathematical equations, allowing scientists to learn how cells work and explore what happens if they are tweaked in certain ways. The newly developed algorithm, Expression Dependent Gene Effects, or EDGE, predicts what happens if scientists manipulate cells to overexpress certain genes. EDGE allows biotechnologists to foresee cases in which the overexpressed genes become toxic and then direct their efforts toward other genes.

To validate their method, TAU researchers used genetic manipulation tools to overexpress 26 different genes in E. coli bacterial cells. Comparing the results of their computer simulations with the actual growth of the overexpressed strains that was measured in the lab, they saw that EDGE was able to predict which of the overexpressed genes turned out to be lethal to E. coli. EDGE was also successful in identifying cases of foreign genes that were toxic to E. coli, as the researchers learned from comparing the simulations' results with data collected by their collaborators at the Weizmann Institute of Science.

Beyond bacteria
EDGE's applications appear to extend beyond bacteria. The researchers conducted tests showing that the genes EDGE predicted to be toxic when overexpressed are expressed at low levels not only in microorganisms like bacteria, but also in multicellular organisms, including humans. The researchers say these results reflect the vital evolutionary need to keep the expression of potentially deleterious genes in check.

"Although EDGE's current focus is biotechnology, gene overexpression also plays a central part in many human diseases, particularly in cancer. We hope that future work will apply EDGE to those directions," Wagner said.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
Diagnostic Test Developed for Enterovirus D68
researchers at Washington University School of Medicine in St. Louis have developed a diagnostic test to quickly detect enterovirus D68 (EV-D68), a respiratory virus that caused unusually severe illness in children last year.
How a Kernel Got Naked and Corn Became King
Ten thousand years ago, a golden grain got naked, brought people together and grew to become one of the top agricultural commodities on the planet.
Sweet Revenge Against Superbugs
A special type of synthetic sugar could be the latest weapon in the fight against superbugs.
New Material Opens Possibilities for Super-Long-Acting Pills
A pH-responsive polymer gel could create swallow able devices, including capsules for ultra-long drug delivery.
How To Keep Your Rice Arsenic-Free
Researchers at Queen’s University Belfast have made a breakthrough in discovering how to lower worrying levels of arsenic in rice that is eaten all over the world.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Computer Model Could Explain how Simple Molecules Took First Step Toward Life
Two Brookhaven researchers developed theoretical model to explain the origins of self-replicating molecules.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!