Navigation Links
Knockouts in human cells point to pathogenic targets
Date:11/26/2009

CAMBRIDGE, Mass. (November 26, 2009) Whitehead researchers have developed a new type of genetic screen for human cells to pinpoint specific genes and proteins used by pathogens, according to their paper in Science.

In most human cell cultures genes are present in two copies: one inherited from the father and one from the mother. Gene inactivation by mutation is therefore inefficient because when one copy is inactivated, the second copy usually remains active and takes over.

In yeast, researchers have it easier: they use yeast cells in which all genes are present in only one copy (haploid yeast). Now Carette and co-workers have used a similar approach and used a human cell line, in which nearly all human chromosomes are present in a single copy.

In this rare cell line, Carette and co-workers generated mutations in almost all human genes and used this collection to screen for the host genes used by pathogens. By exposing those cells to influenza or to various bacterial toxins, the authors isolated mutants that were resistant to them. Carette then identified the mutated genes in the surviving cells, which code for a transporter molecule and an enzyme that the influenza virus hijacks to take over cells.

Working with Carla Guimaraes from Whitehead Member Hidde Ploegh's lab, Carette subjected knockout cells to several bacterial toxins to identify resistant cells and therefore the genes responsible.

The experiments identified a previously uncharacterized gene as essential for intoxication by diphtheria toxin and exotoxin A toxicity, and a cell surface protein needed for cytolethal distending toxin toxicity.

"We were surprised by the clarity of the results," says Jan Carette, a postdoctoral researcher in the Brummelkamp lab and first author on the Science article. "They allowed us to identify new genes and proteins involved in infectious processes that have been studied for decades, like diphtheria and the flu. In addition we found the first human genes essential for host-pathogen interactions where few details are known, as is the case for cytolethal distending toxin secreted by certain strains of E. coli. This could be important for rapidly responding to newly emerging pathogens or to study pathogen biology that has been difficult to study experimentally."

Brummelkamp sees the work as only the beginning.

"Having knockout cells for almost all human genes in our freezer opens up a wealth of biological questions that we can look at," he says. "In addition to many aspects of cell biology that can be studied, knockout screens could also be used to unravel molecular networks that are exploited by a battery of different viruses and bacteria."


'/>"/>

Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert  

Related biology news :

1. Gene regulation, not just genes, is what sets humans apart
2. Antioxidant overload may underlie a heritable human disease
3. Facial attraction -- choice of sexual partner shaped the human face
4. Humans fostering forest-destroying disease
5. SRMs track fire retardants in humans and environment
6. St. Jude influenza survey uncovers key differences between bird flu and human flu
7. Human derived stem cells can repair rat hearts damaged by heart attack
8. Influence of sex and handedness on brain is similar in capuchin monkeys and humans
9. Gene regulation in humans is closer than expected to simple organisms
10. Pittsburgh scientists identify human source of stem cells with potential to repair muscle
11. Researchers developing device to predict proper light exposure for human health
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Knockouts in human cells point to pathogenic targets
(Date:4/18/2017)... April 18, 2017  Socionext Inc., a global expert in SoC-based ... edge server, the M820, which features the company,s hybrid codec technology. ... by Tera Probe, Inc., will be showcased during the upcoming Medtec ... show at the Las Vegas Convention Center ... Click here ...
(Date:4/11/2017)... Apr. 11, 2017 Research and Markets has ... report to their offering. ... The global eye tracking market to grow at a CAGR of ... Eye Tracking Market 2017-2021, has been prepared based on an in-depth ... market landscape and its growth prospects over the coming years. The ...
(Date:4/5/2017)... , April 5, 2017 Today HYPR ... that the server component of the HYPR platform is ... providing the end-to-end security architecture that empowers biometric authentication ... HYPR has already secured over 15 million users across ... manufacturers of connected home product suites and physical access ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , ... of Cancer Research, London (ICR) and ... with SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple ... as MUK nine . The University of ... is partly funded by Myeloma UK, and ICR will perform ...
(Date:10/11/2017)... ... October 11, 2017 , ... ... and pregnancy rates in frozen and fresh in vitro fertilization (IVF) ... maternal age to IVF success. , After comparing the results from the fresh ...
(Date:10/10/2017)... (PRWEB) , ... October 10, 2017 , ... San Diego-based ... of its corporate rebranding initiative announced today. The bold new look is part ... as the company moves into a significant growth period. , It will also expand ...
(Date:10/10/2017)... ... 10, 2017 , ... For the second time in three ... Mentoring Award. Representatives of the FirstHand program travelled to Washington, D.C. Tuesday, October ... US2020’s mission is to change the trajectory of STEM education in America by ...
Breaking Biology Technology: