Halobacteria

Researchers at Seattle’s Institute for Systems Biology (ISB) have discovered how a group of organisms that thrive in places with conditions that would kill most living things —such as hot springs, geysers, and salt ponds — rapidly adapt to changing conditions.

The trick, the researchers report, is the organisms’ ability to alter the activity of a group of proteins that, in turn, rapidly reset many of the organisms’ functions simultaneously.

These proteins, called general transcription factors, have long been thought to operate primarily in the background, playing a quiet, supporting role in the process of gene expression.

But new findings suggest these factors play a more important regulatory function than previously though and a fundamental role in evolution, says Nitin Baliga, Ph.D., director of Integrative Biology at the institute, who led the research team.

The paper was published online by the journal Molecular Systems Biology.

The findings not only shed light on how living things evolve, they may also help increase our understanding of the role that the human counterparts of these factors play in human health and disease, says the paper’s lead author ISB research scientist Serdar Turkarslan.

Extremophiles can thrive in geysers and hot springs.

The focus of the Seattle team’s study was Halobacterium salinarum, a microscopic, single-celled organism that can thrive in super-salty environments like the the Great Salt Lake and the Dead Sea and even in salt evaporation ponds. These are the organisms that give such high-salt waters their sometimes pinkish tinge.

H salinarum belong to a group of organisms often called extremophiles (extreme + loving), because members of this group are found  living in extreme environments.

Indeed, these organisms can live in water ten-times saltier than the sea, in temperatures as high as 235 degrees F (113 C), and in highly acidic conditions with a pH as low as zero.They are also found in oxygen-poor environments such as deep-sea sediments — and the human gut.

Archaea

Halobacterium salinarum are from a group of extremophiles called archaea.

Although the archaea were first discovered in the 1970s in extreme environments, they have been found in many environments, and it is estimated that they make up about 20 percent of the earth’s biomass.

The archaea were originally grouped with the bacteria, but now are considered to be their own unique group because they have a different evolutionary history and a unique biochemistry.

Like bacteria, they lack nuclei, but the way they process the genetic information encoded in their DNA more closely resembles the processes seen in eukaryotes, including humans. “They look like bacteria,” says Baliga, “but they are in many ways simplified eukaryotic cells”

This makes them interesting organisms to study, Baliga says: because they are simple, they are easy to grow and tinker with; but because their molecular machinery more closely resembles that of eukaryotes, studying them can provide better insights into the molecular biology of eukaryotic, including human, cells.

Transcription Factor B

The proteins in these cells Baliga and his team were interested are a group of proteins called general transcription factors, in particular transcription factor B, or TFB.

These factors affect the activity of hundreds, even thousands of other genes, so a change in their function can have a widespread effect throughout a cell.

What was particularly interesting to the ISB researchers was that the archaea had so many copies of TFB genes, up to eleven. “Researchers wondered if only one copy was necessary, what are the other copies doing?’ Baliga said.

In addition, not only were the curiously large number of TFB genes, there also seemed to be a clear pattern to their evolution: Archaea that live in high temperature environments, for example, appeared to develop one set or “lineage” of TFBs , while those that are able to live in low oxygen environments another, and those that live in saline environments yet another.

It appeared that in Archaea, at least, TFBs doing more than just playing a quiet, supporting role in the background. “It was an observation that was hard to ignore,” says Baliga.

ISB researchers Baliga and Turkarslan

Duplication

By tracing the family tree of the archaea, researchers have worked out that the organisms had accumulated TFB genes through a process called duplication.

Duplication is a common way cells create new genes. Indeed, about 90 percent of the genes in our chromosomes arose through duplication.

In this process, an organism makes an extra copy of a gene. Now, with two copies of the gene, it is possible for one of the copies to mutate without harming the cell.

The cell survives because, as one copy mutates, the other copy continues to do the gene’s original job. With time and chance the mutating gene can evolve to a new form that gives the organism a new ability.

“For some period of time, the genes would have the same function,” says Baliga. “But one gene can mutate as long as there is a second copy that continues to do the gene’s original tasked function. And, voila, eventually you have two genes that came from the same original gene that now have two functions.”

If that new function allows the cell to adapt to a change in the environment, say it allows the cell to handle higher temperatures, the organism now has an advantage over cells that do not have the new gene and is more likely to survive in a hotter environment.

What is Systems Biology?

“Systems biology is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life. Instead of analyzing individual components or aspects of the organism, such as sugar metabolism or a cell nucleus, systems biologists focus on all the components and the interactions among them, all as part of one system.”

From the ISB Intro to Systems Biology more…

In the new study, Baliga and his colleague wanted to find out what role the different TFB genes might play in helping in H salinarum adapt to different environments.

So what they did was grow the cells in different conditions, varying the temperature, salinity and concentration of copper, a potentially toxic element in high enough concentrations.

Cells that grew better in one environment were deemed to be more “fit” for that environment than those that did not.

Then, using the systems biology approach, the team measured the activity of the different TFB genes in the different conditions and the effect they had on other genes and proteins throughout the cell.

They also tinkered with the cells, sometimes removing the genes for different TFBs, sometimes inserting genes, and repeating the experiments to see what effect the loss or addition of a particular TFB had on the cell’s “fitness”.

All in all they ran nearly 2,500 experiments, generating millions of data points on gene expression, protein activity and other factors, which they then analyzed using powerful computer algorithms.

What they found was that the different TFBs, either alone or in combination, did, indeed, allow the cells to better survive in radically different environments. In some environments, one TFB or a combination of TFBs, was crucial. In other environments, and another set of factors was important.

Expanded genetic “toolbox”

The findings suggest that by having several types of TFBs, the archaea have on hand in their genetic “toolbox” the means to quickly adjust to a variety of new conditions.

“The result is a simple, efficient way for these cells to rapidly acclimate to a changing environment,” says Baliga. “It gives them the flexibility to adapt.”

In nature, this means in a population of archaea living in a salt pond that suddenly begins to dry up and become more salty, some of the cells are more likely to have a mutated version of a TFB on hand that will allow the cells to adjust and survive in the new environment. Subsequent generations would then be able to evolve even more to be even better adapted to the new environment.

The findings not only shed light on a “fundamental mechanism of evolution”, says Baliga, it gives us insight into the biology of a the archaea, a class of organisms that makes up a substantial, if little understood part of life on earth.

Baliga says that one of the first practical uses of the research may be to engineer artificial TFBs that would make it possible for archaea to survive in highly toxic environments, such as that created by a toxic spill, where the organisms could break down the toxins and render them harmless.

The archaea could also be used as models in research into the roles TFBs play in a wide variety of human diseases, including heart disease, cancer, and a number of inherited conditions, Baliga said.

To learn more:

• Read Baliga and Turkarslan’s paper: Niche adaptation by expansion and reprogramming of general transcription factors.

• Visit the Institute for Systems Biology’s website.

Photo by Bies

By Martha Bebinger, WBUR
This story is part of a reporting partnership that includes WBUR,  and Kaiser Health News.

There are lots of reasons why an expectant mother and her doctor might choose to deliver the baby before its due date: the health of mom or baby, the doctor’s schedule, the demands of work, or even to hit or avoid a specific birthday.

But if that perfect day falls before the 39th week of pregnancy, and there’s no medical reason for an early delivery, many hospitals in Massachusetts are saying no, you have to wait.

“Before the benefit of the neonatal intensive care unit, people were very conservative and would not induce or do repeat C-sections before 39 weeks,” says Dr. Glenn Markenson, the director of maternal and fetal medicine at Bay State Medical Center in Springfield. “But as they saw how well babies were doing with pediatric care, and they were getting pressured by patients because of social situations, there was a creep down from 39 weeks to 38 weeks, sometimes 37 weeks.”

Expensive neonatal care has allowed babies born very early to survive, and even thrive. Yet, this success has eclipsed the fact that babies born even a bit early are at a higher risk for a variety of problems.

“Early-term infants have higher rates of respiratory distress. There are also issues with feeding,” says Dr. Lauren Smith, medical director at the state Department of Public Health. “The most recent evidence shows that babies born before 39 weeks may also have developmental issues, so when you add up the increased risks and you weigh that against a situation when it’s purely elective, then you really can’t justify it.”

A growing number of hospitals in Massachusetts, and across the country, are saying no to elective inductions and C-sections before 39 weeks. The change is happening quietly and some new mothers don’t like it.

“The bottom line is women should have 99 percent of the say in what happens with their pregnancy and their bodies,” says Coulouris, who delivered twins eight months ago after complications that led to an emergency C-section. She does not like the idea of hospitals telling women they must carry to at least 39 weeks.

Doctors who are trying to end early elective deliveries say they don’t have a savings goal. Their focus right now is on reversing the trend.

“You’re already out of control of your body, so at least to know if you go to your doctor’s office and say, ‘Look, we’re at 37 weeks, and I feel like I’m ready,’ ” Coulouris says, imagining a case in which a mom would not want to wait. “To know that I would have that choice would just make me feel better. But to take it away from me just adds to the pressure of being pregnant.”

Across the room, Jennifer Brickley agrees that doctors need to take a mom’s emotional state into account, but she is bothered by the rise in what she calls “convenient deliveries.”

“In recent years it’s kind of gotten in line with the spa appointments or the hair appointments,” says Brickley, who supports timing a delivery based on medical evidence. “So I agree with what they are doing. Probably it’s a lot of costs involved that are driving this as well.”

Doctors who are trying to end early elective deliveries say they don’t have a savings goal. Their focus right now is on reversing the trend. Some hospitals have installed scheduling software that rejects deliveries before 39 weeks.

At Massachusetts General Hospital, Dr. Jeff Ecker, a high-risk obstetrician, is the gatekeeper. Each week Ecker reviews the schedule for early inductions and C-sections to see if they are all medically necessary. He says the decisions are easy when either the date is clearly a choice or the mother or baby is very sick.

“And in between are sometimes shades of gray – how high is the blood pressure, how small is the baby?” he says.

Privately, some obstetricians worry about how hospitals that stop early elective deliveries will handle cases that aren’t clear-cut.

Ecker says he tries to make sure that physicians and patients weigh the risks of an early birth against the pregnancy complication they face. He says physicians at Mass. General, when presented with the evidence, have largely stopped requesting early elective deliveries.

“Our goals are to make it virtually a never event, so there will not be truly elective deliveries less than 39 weeks, and we’re pretty much there,” he says.

In health care, a “never event” is the equivalent of a medical mistake for which hospitals may not get paid under Massachusetts law. That’s not the case yet with early elective deliveries.

PHOTO: Courtesy of Bies.

This article was reprinted from kaiserhealthnews.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente.

RNA interference (RNAi) is an important pathway that is used in many different organisms to regulate gene expression. This animation introduces the principles of RNAi involving small interfering RNAs (siRNAs) and microRNAs (miRNAs).

We take you on an audio-visual journey through the steps of gene expression and show you an up-to-date view of how RNAi can silence specific mRNAs in the cytoplasm.

Animation by Ballard-based Arkitek Studios.

To learn more:

• Go to the Nature Reviews Genetics webpage where you can find additional information and a poster in a pdf file.
• Visit Arkitek Studios.

Every week, reporter Jessica Marcy selects interesting reads from around the Web.

The New York Times Magazine: A Drug That Wakes The Near Dead

Zolpidem Photo by Miserlou via Wikipedia

The heart attacks never came. Four days later, Chris woke up. It was not the awakening of Hollywood movies in which the patient comes to, just as he was, speaking full sentences and completely mobile.

Three years later, Chris still cannot talk. Although he breathes on his own, his lungs battle a steady barrage of infections; a feeding tube provides all his sustenance, and his muscles have contracted into short, twisted knots. He can move only the slightest bit. … Still, Wayne and Judy say that his cognition is improving. … Convinced that the son they know and love is still “in there,”

Chris’s parents have spent the past three years searching for a way to bring him back out. So far, their best hope has come from an unlikely source: Ambien. A growing body of case reports suggests that the popular sleep aid can have a profound — and paradoxical — effect on patients like Chris.

Rather than put them to sleep, both Ambien and its generic twin, zolpidem, appear to awaken at least some of them. The early reports were so pronounced that until recently, doctors had a hard time believing them.

Only now, more than a decade after the initial discovery, are they taking a closer look (Jeneen Interlandi, 12/1).

Image by Miserlou via Wikipedia — Creative Commons license

The Weekly Standard: Romneycare And Abortion

Mitt Romney by Jessica Rinaldi

Mitt Romney erased any doubt that he’s playing to win the Iowa caucuses when he rolled out his first campaign ads in the Hawkeye State last week. A glossy paper mailer pitched Romney to socially conservative Iowans as “the strongest Republican to beat Barack Obama and protect our values.”

Romney’s “pro-life,” “pro-marriage,” and “pro-family” credentials were the three bullet points. “Mitt Romney lives his values,” read the “pro-family” text, as reported by the Des Moines Register. … Romney doesn’t need to win Iowa’s social conservative activists, but he does need to allay the concerns of enough social conservatives to win the state—and the nomination.

Vander Plaats says that one big stumbling block for Romney is the Massachusetts health care law’s coverage of elective abortions. … Taxpayer funding of abortion is highly unpopular among the general electorate and outright toxic with Republicans.

Voters opposed public funding of abortion by 72 percent to 23 percent in a 2009 Quinnipiac poll. Republicans opposed it by an eye-popping 91 percent to 5 percent. … The question for socially conservative Republicans isn’t whether Romney’s perfect—it’s compared to what (John McCormack, 12/12).

Photo: Jessica Rinaldi via Wikipedia under Creative Commons license.

Huffington Post: Low Birthweight May Take A Toll On Cognitive Abilities Later In Life

At just 2 pounds, 15 ounces, Deb Discenza’s daughter was what doctors and researchers consider a very low-birthweight baby. Discenza, who is co-founder of PreemieWorld and author of “The Preemie Parent’s Survival Guide to the NICU,” said she received ample information and that doctors gave her daughter plenty of care.

But one area that they virtually ignored was the potential impact her daughter’s small size at birth might have on her cognitive abilities down the road. … But eight years later, that may finally change. A new, Finland-based study published in the journal Neurology on Monday suggests that very low-birthweight babies — those under 3.3 pounds — scored lower than normal birthweight babies when researchers considered their general intelligence, attention, visual memory and executive functioning as adults.

The latest report joins prior studies that have suggested that severely preterm babies do worse on neurocognitive tests.

To look at the potential impact of birthweight on the brain, the authors of the new study compared approximately 100 adults with very low birthweight and approximately 100 who had not had very low birthweight (Catherine Pearson, 12/5).

American Medical News: How Technology Can Connect Doctors And Caregivers

With more than 29% of the U.S. population acting as a caregiver to someone else, chances are that physicians eventually will be faced, as Dr. Manaker is, with questions about how they can work with caregivers to ensure the health of the person receiving care. The majority of caregivers spend an average of 20 hours per week providing care, in addition to holding down a full-time job.

To help make things more efficient, many are turning to technology that not only will supplement the care they are providing in person, but also will help them stay organized and connected with the care recipient’s physicians or fellow caregivers.

The more physicians can help get the needed technology to caregivers, experts say, the easier those caregivers’ lives will be.

Likewise, the more engaged the caregiver is, the better the outcomes for patients. … A study published in January by the National Alliance for Caregiving and UnitedHealthcare found that caregivers think technology can help save time (77%), manage the logistics of caregiving more easily (76%), increase feelings of effectiveness as a caregiver (74%), reduce stress (74%) and make a care recipient feel safer (75%) (Pamela Lewis Dolan, 12/5).

Huffington Post: Trisomy 18: What Is The Disease Affecting Rick Santorum’s Daughter?

Few politicians have wed their political and family lives quite like GOP presidential candidate Rick Santorum. Frequently hitting the campaign trail with his wife and children by his side, the father-of-seven has spoken publicly and intimately about tragedies his family has faced over the years, including a stillborn baby that became the focus of a 2005 Washington Post article.

Now the Santorum family is faced with another tragedy: the life-threatening illness of their 3-year-old daughter Bella, who suffers from Trisomy 18.

The genetic disorder is in the same category of the disease affecting Sarah Palin’s son Trig, who was born with Trisomy 21, or Down Syndrome.

Like Trig Palin, Bella Santorum has become a central figure in her parent’s presidential campaign, inspiring both praise for Santorum and criticism from those who believe he may be using her condition to further his agenda of fighting healthcare reform legislation (Jocelyn Richard, 12/5).

This article was reprinted from kaiserhealthnews.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente.

Heather Kirkwood, a HPS patient who stars in the film and serves as Director of Outreach/VP for the HPS Network, will facilitate our discussion and take questions following the film.

When:

• Tuesday, December 13, 5:30 to 7:30 P.M.

Where:

• 415 Westlake at Kakáo Chocolate & Coffee, Seattle.

Cost: 

•  $10 at the door

Note: Attendance by RSVP

Click here to RSVP or call 206-957-3337×306,