Featured Research

from universities, journals, and other organizations

Scientists Get Look At Genes' Defensive Playbook; Study Tracks Human Genomic Response To Inflammation

Date:
September 1, 2005
Source:
University of Florida
Summary:
More than 15 percent of our genes are mobilized to defend against infections in the bloodstream. The study represents a major step in understanding inflammation in severely injured or burned patients.

GAINESVILLE, Fla. -- Using a new method to identify networks ofinfection-fighting genes, scientists writing in today's (8-31) onlineedition of Nature say more than 15 percent of our genes are mobilizedto defend against microbial attacks.

Related Articles


The body's overwhelming genetic defense, which has implications forthe survival of patients who are severely burned or injured, wasrevealed in a sweeping analysis of gene activity in volunteers who wereinjected with a bacterial product that temporarily created flu-likesymptoms.

"During a 24-hour period, the expression of more than 3,700genes changed in blood leukocytes," said Lyle Moldawer, Ph.D., asurgery professor in the University of Florida College of Medicine,part of the national consortium that published the findings. "It was adramatic reprioritization of genes. But beyond individual genes, wewere able to look at networks, or functional modules of different geneclusters, that change in concordance with one another. We have nowidentified previously unknown relationships among different genes thattell us in greater detail how blood cells respond to an infectiouschallenge."

Inflammation is part of normal healing when people are severelyburned or injured, but in some patients, it can be fatal, causingbloodstream infections and multiple organ failure. Learning how and whyinflammation becomes harmful will help doctors more accurately predicthow each injured patient will fare.

"This work represents a major step in understandinginflammation in severely injured or burned patients," said Jeremy M.Berg, Ph.D., director of the National Institute of General MedicalSciences, the component of the National Institutes of Health thatfunded the research. "We hope this knowledge eventually will helpphysicians better predict patient outcomes and tailor treatmentsaccordingly."

UF Genetics Institute researchers are part of a national groupof scientists united by a five-year, $37 million "glue grant" from theNIGMS. Glue grants bring together scientists from diverse fields -- inthis case surgery, critical care medicine, genomics, bioinformatics,immunology and computational biology -- to solve problems in biomedicalscience that no single laboratory could address.

Scientists injected healthy volunteers with a microbialproduct that temporarily causes nausea and fever, triggering naturalimmune responses. The condition is similar to sepsis, which can happenwhen the body's infection-fighting white blood cells spring intoaction, causing potentially harmful inflammation in the process.

"Basically we made the volunteers appear septic for a couple ofhours and examined changes in the gene expression from their whiteblood cells," Moldawer said. "Such genomic analyses give us the abilityto simultaneously survey the activity of every gene in the cell, givingus vast lists of genes that change in response to stimulation. Itprovides us with an unprecedented amount of data."

To make sense of the enormous amount of information,researchers plugged their list of nearly 4,000 gene changes into adatabase of interactions of known human and mouse genes developed byIngenuity Systems Inc. of Mountain View, Calif. The results identifiedthe networks of genes that helped the body respond to the challenge.

"We were able to identify changes in functions that we neverwould have seen before," Moldawer said. "For example, the ability ofthe infection-fighting cells to make energy appeared to bedown-regulated, as if the cells were shutting down all other functionsnot required to rid the body of the bacteria. This may well be thesignal that something is wrong with the cell and may be a reason whysome patients who are injured or infected go on to develop organfailure."

With that knowledge, scientists may be able to look at new waysto re-establish stability within the cells and avert the negativeconsequences of infection fighting.

"The apparent repression of genes that occurs has never beenfully appreciated," said Henry Baker, Ph.D., associate director of theUF Genetics Institute and director of the UF lab that performs genomicanalyses for the consortium. "Initially, more than half of the genesbecame less active, but over the long haul, they were more focused onthe inflammatory response. By drawing samples for analysis over sixtime points in 24 hours, we were able to infer the sequence of eventsand how some changes in gene expression cause other changes."

Additional genomic analysis took place at the Stanford GenomeTechnology Center in Palo Alto, Calif., and the department of surgeryat Washington University in St. Louis, Mo.

The research is particularly valuable because it plotsinflammatory response over time, according to Scott D. Somers, Ph.D.,NIGMS program director of this glue grant.

"In the case of injury, time is critical," Somers said. "Toprovide the best treatment, doctors need to know how the human bodyresponds in the moments and days after an injury. No other study ofinjury or inflammation has tracked changes to the entire human genomeover time."

The glue grant team includes scientists from the UF College ofMedicine; Stanford; Washington University; the University of Medicineand Dentistry of New Jersey-Robert Wood Johnson Medical School in NewBrunswick, N.J.; Ingenuity Systems Inc.; the University of RochesterSchool of Medicine in Rochester, N.Y.; and Massachusetts GeneralHospital, Harvard Medical School in Boston.


Story Source:

The above story is based on materials provided by University of Florida. Note: Materials may be edited for content and length.


Cite This Page:

University of Florida. "Scientists Get Look At Genes' Defensive Playbook; Study Tracks Human Genomic Response To Inflammation." ScienceDaily. ScienceDaily, 1 September 2005. <www.sciencedaily.com/releases/2005/09/050901075436.htm>.
University of Florida. (2005, September 1). Scientists Get Look At Genes' Defensive Playbook; Study Tracks Human Genomic Response To Inflammation. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2005/09/050901075436.htm
University of Florida. "Scientists Get Look At Genes' Defensive Playbook; Study Tracks Human Genomic Response To Inflammation." ScienceDaily. www.sciencedaily.com/releases/2005/09/050901075436.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins