Navigation Links
Knockouts in human cells point to pathogenic targets

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
Whitehead Institute for Biomedical Research

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:
Related Image:
Knockouts in human cells point to pathogenic targets
(Date:6/22/2016)... On Monday, the Department of Homeland Security ... solutions for the Biometric Exit Program. The Request for ... (CBP), explains that CBP intends to add biometrics to ... United States , in order to deter visa ... Logo - ...
(Date:6/9/2016)... , June 9, 2016  Perkotek an innovation leader in attendance control systems ... seamlessly log work hours, for employers to make sure the right employees are actually ... ... ... ...
(Date:6/2/2016)... 2, 2016   The Weather Company , an IBM ... an industry-first capability in which consumers will be able to ... ask questions via voice or text and receive relevant information ... Marketers have long sought an advertising solution that ... be personal, relevant and valuable; and can scale across millions ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica delle Marche in ... peritoneal or pleural mesothelioma. Their findings are the subject of a new article on ... biomarkers are signposts in the blood, lung fluid or tissue of mesothelioma patients that ...
(Date:6/23/2016)... ... June 23, 2016 , ... UAS LifeSciences, one of the ... brand, UP4™ Probiotics, into Target stores nationwide. The company, which has been manufacturing ... to its list of well-respected retailers. This list includes such fine stores as ...
(Date:6/23/2016)... , June 23, 2016 /PRNewswire/ - FACIT ... Ontario biotechnology company, Propellon Therapeutics ... development and commercialization of a portfolio of first-in-class ... Epigenetic targets such as WDR5 represent an exciting ... significantly in precision medicine for cancer patients. Substantial ...
(Date:6/23/2016)... 2016 Houston Methodist Willowbrook Hospital has ... Association to serve as their official health care ... Willowbrook will provide sponsorship support, athletic training services, ... coaches, volunteers, athletes and families. "We ... Association and to bring Houston Methodist quality services ...
Breaking Biology Technology: