Inching Toward an Understanding

C. elegans is a roundworm being used in correlational research to observe gene expression in humans

By: Kristen Kocher

Humans and worms are more alike than you may realize. According to a genetic researcher at the University of Toronto, Dr. Andrew Fraser, the worm (C. elegans) is his preferred specimen for genomic studies. “I think worms are totally cool, like humans only simpler and easier,” Fraser comments. It is important to understand that we are not only in the same phylogenetic domain (Eukarya) and kingdom (Animalia) as worms, but between us we share nearly 10,000 comparable genes. This makes worms like C. elegans an excellent vehicle for understanding human genetics and genetic disease without actually studying or experimenting on human beings.

With a genome a little less than half the size of that of humans, it is easier for geneticists to perform certain research techniques that would be very difficult to perform on humans. One such technique is known as RNA interference (RNAi), which shuts down one gene at a time and allows researchers to observe and catalogue specific gene function and possible interactions with other genes. Discovered by Andrew Fire and Craig C. Mello, RNAi is a very effective method of “gene silencing” and is found naturally in worms. Scientists have been able to harness this innate phenomenon and use it to their advantage in understanding the way similar genes between worms and humans function. Geneticists face the challenge of understanding how genes in any organism are expressed phenotypically. Phenotype is the “final outward expression” of an organism’s genetic makeup. In worms, however, it is slightly easier to observe the expression of certain genes when RNAi is occuring because of their drastically simpler genome.

Fraser suggests that his research with worms will aid in predicting “the effects of inherited mutations and to understand how multiple mutations combine to be expressed phenotypically.” This work will further help in understanding how inherited mutations cause health problems in humans. Fraser makes a point of noting that humans do not exist in a controlled environment like the worms being studied in his lab. To account for this, Fraser has decided to also isolate worms from certain natural environments exposed to different conditions, providing an interesting insight as to how certain environmental factors contribute to mutations within a population.

Dr. Fraser is conducting keystone research that will hopefully provide a foundation for other types of genomic research. At the annual AAAS conference this year, Fraser will explain his research and the use of C. elegans to provide interesting conclusions as to both individual and population genetics and genetic disease for not only humans, but numerous other species within the kingdom Animalia.

Check out the original Press Release

Taking the flight (and bite) out of the pesky mosquito

By Liz H.

The bite of the female Aedes aegypti mosquito can transmit the virus that causes Dengue fever to humans
The bite of the female Aedes aegypti mosquito can transmit the virus that causes Dengue fever to humans.

The days of the flying mosquito may be drawing to a close.  In a study published in the February 22nd issue of the Proceedings of the National Academy of Science, a team of American and British researchers report that they have engineered a mosquito in the lab that produces offspring that cannot fly and consequently cannot infect humans with the virus that causes Dengue fever (full article).  Their findings may lead to a sustainable mosquito population suppression strategy that dramatically reduces human morbidity and mortality from a variety of diseases transmitted by mosquitoes.

In this study, the scientists specifically focused on the Aedes aegypti mosquito that causes Dengue fever.  The researchers manipulated the genetic material of the males of this species in the lab to carry a novel trait:  the inability to fly.  When these modified males were mated with normal, wild-type females, they passed the trait on to their female offspring.  By rendering the female offspring flightless, the scientists effectively imposed a death sentence on this group.  If the females cannot fly, they cannot elude predators, mate with males, escape from water, or seek out human blood.  Most importantly a flightless female may lead to the eradication of Dengue fever, since the disease is transmitted by the bite of female Aedes aegypti mosquitos.

The researchers predict that 6-9 months after introducing the modified males into the wild, the wild-type females in the area will be completely replaced by the flightless offspring of the modified males.  This is big news with important applications in the control of mosquito-borne disease.  This method of control offers several advantages over traditional techniques because it specifically targets the species of mosquito that causes Dengue fever and bypasses the use of toxic insecticides.  And as senior author Luke Alphey notes, “Another attractive feature of this method is that it’s egalitarian: all people in the treated areas are equally protected, regardless of their wealth, power or education.”

The next step for the researchers is to study the mating competitiveness of the modified males in the wild and whether their flightless female offspring will actually suppress the wild-type population as predicted.  Additionally, the methods used by these scientists could be adopted to control other species of mosquitoes that spread serious diseases such as West Nile virus and malaria.

Dengue fever is a flu-like illness with no vaccine or treatment that infects 50-100 million people each year in over 100 countries in tropical and subtropical climates, including Puerto Rico and tourist destinations in Latin America and Southeast Asia.  It is the most common mosquito-borne disease and the CDC estimates that one third of the world’s population lives in areas where the disease is endemic.  Other diseases transmitted by mosquitoes include West Nile virus, malaria, Rift Valley Fever, and Yellow fever.  Taken together, these illnesses represent growing public health issues that require effective and sustainable mosquito population control measures.  The flightless mosquito may just be the answer to this urgent problem.

Want more information?

Press release

CDC site on Dengue fever

Air Pollution: A Radiation Umbrella

By: Kate Good

In the world of climate change there is much debate over the reality of greenhouse gases and the volatile nature of toxic chemical emissions. However, in a new study, published February 17, 2010, scientists are beginning to look at air pollution as a possible inhibitor of global warming.

The thick black clouds of smog produced from coal burning power plants in Asia seem to be having the reverse effect of warming in the atmosphere. In fact, the dark layer acts like an umbrella, blocking the sun’s radiation from reaching Earth’s surface reflecting them back into space.

The most recent work being done on the climate effects of air pollution is being done in New York at NASA’s Goddard Institute for Space Studies, led by scientist Drew Shindell.

In Shindell’s study, a number of scenarios have been run for the years 2000-2080, putting controls on the output of SO2 and NOX from power plants. While initially SO2 creates a cooling effect, when unchecked, once controls are put on the warming potential of CO2 comes into effect. When run for longer time trials, without controls on SO2, the effects of CO2 eventually catch up to SO2, eliminating the net cooling effect.

In the 1970’s, the United States began the Clean Air Act, which cut emissions of SO2 and NOx to reduce acid rain and to improve public health. Many other industrial countries followed curbing their own emissions, interestingly, during this period global temperatures increased rapidly after having been stable in the preceding decades.

If having high levels of air pollution in fact produces lower global temperatures, all the work done by environmentalists in the past will be completely void.

Meinrat Andreae, an expert on aerosols from the Max Planck Institute for Chemistry in Mainz, Germany, is quoted describing this phenomenon as,  “enjoy now and make others pay later.”

While SO2 may seem like a good temporary fix to rising global temperatures, it is also a deathly chemical. Sulfur dioxide is associated with increased respiratory disease, difficulty in breathing and premature death. So, even though this chemical may aid in blocking the sun’s radiation, it is still a harsh chemical compound that is harmful to humans when present in air.

A Human Powered Future? Maybe.

Dan Conant
What the chip would look like

 

With all sorts of alternative energy sources vying to prove themselves the cheapest and cleanest of them all, human generated energy has recently made a big stride due to a new piece of technology from Princeton.  However, before you begin to think of something similar to the Matrix with humans being plugged into a power grid, it is important to note that humans will not generate mass quantities of energy.  This is because the energy generated is by our muscles movement, not by the small but frequent electrical impulses that trigger muscle movement. 

Princeton University engineers created a chip composed of ceramic and rubber nanoribbons.  This allows the chip to be able to flex.  The idea behind the chip is that when a muscle moves, this chip attached to it will also flex and by doing so, create a small amount of energy.  The chip is also fairly efficient in terms of energy conversion, turning mechanical energy into electrical energy at an efficiency rate of 80%. 

This chip is very important to the many fields of medicine.  There are currently a number of medical devices such as implants that require a source of energy.  Currently batteries fill this role, but when they begin to run out of energy, the patient has to undergo another surgery to have another battery put in.  With this chip implanted, repeated operations would never have to happen again unless the chip became damaged or the pacemaker was having issues.  For someone with a pacemaker, this chip would be implanted near the lungs due to its proximity to the heart as well as the constant movement of a person’s lungs due to breathing would provide a consistent a steady source of energy for the pacemaker. 

This is not the first human powered energy converter to have been conceived, but it is arguably one of the best ones.  Due to the materials in the chip, the body should also accept the chip with no issues.  Furthermore, due to the simplicity of the chip and the materials not costing too much, chips like these should become affordable soon after their debut and mass production; certainly a relief for the many people out there with heart problems and wallet problems.

Information for this article was gathered from this link.

Parachuting into Combat: If the bullets don’t get you, the ground will

      When parachuting out of a plane into combat, there are two competing considerations at play. The soldier needs to reach the ground as quickly as possible (spending as little time in the air as an easy target for enemy fire as possible) without being injured on landing.

      This first goal means that military parachutes do not provide the softest possible landings, and poor landing technique often leads to injuries. What happens when you add over 100lbs. of body armor, weaponry, ammunitions, communications equipment, and other combat gear to this equation?

      A study carried out in January of 2010 at the University of Pittsburgh has demonstrated that the extra weight from combat equipment can alter soldiers’ landing mechanics and lead to increased incidence of musculoskeletal injury.

      In this study, researchers compared the kinetics (the relationship between the motion of a body and the forces acting on it) of the landings of 70 active duty Air Assault soldiers with and without equipment. High-speed cameras and computer software were used to capture and analyze the soldiers’ landing biomechanics under the two conditions, and force plates were used to measure vertical ground reaction forces (force exerted by the ground on a body in contact with it) of the landings.

      Soldiers performed two-legged drop landings from a height of less than two ft. with body armor, helmet, and rifle, weighing a total of less than 40lbs. Real parachute landings are more similar to dropping from a height of ten feet without a chute, and real weight of combat gear exceeds 100lbs. Even though experimental forces were far less than those typically experienced by soldiers in training and combat, the additional weight was still observed to significantly alter soldiers’ landings.

      It was determined that with the additional weight, soldiers experienced significantly greater maximum knee flexion, significantly greater maximum ground reaction forces, and greater time between initial ground contact and these peak values.

      These changes in landing biomechanics and force of impact increase the risk of musculoskeletal injuries in soldiers. Such injuries are a primary concern in the military. The Armed Forces Epidemiological Board reports that musculoskeletal injuries “impose a greater ongoing negative impact on the health and readiness of U.S. Armed forces than any other category of medical complaint during peacetime and combat.” According to records, 58% of hospitalization cases in 2005 in the Navy were due to musculoskeletal injuries. These types of injuries result in significant amounts of lost duty time and can often be long-lasting and difficult to make a full recovery from, so prevention is crucial.

      While jumping into combat without equipment is obviously not an option, proper strengthening and conditioning of the lower extremities, incremental increases in the weight with which soldiers train, and emphasis on proper landing technique can help mitigate the increased risk of injury associated with the weight of combat gear.

Nicole Myers

For more information follow: http://proquest.umi.com/pqdlink?Ver=1&Exp=02-21-2015&FMT=7&DID=1954679781&RQT=309

Where can I get that gene “juice”?

By Abby Larson

Athletes are competitive by nature, and many will do whatever they can to win.  Steroid usage is heavily monitored in competitions, yet with the coming of the Winter Olympics, whispers of “gene doping” are becoming audible. There has been a craze by athletes for “gene juice” ever since a 2005 study performed by Dr. Ronald Evans, a geneticist at the Salk Institute for Biological Studies in San Diego, California, produced the “Marathon Mouse”.  Evans discovered a gene involved in muscle formation and altered it, producing a mouse that could run twice as far as normal mice.  This spurred the World Anti-Doping Agency (WADA) to list gene doping as illegal.

Evans was searching for a way to treat muscular dystrophy, characterized by muscle wasting and inability to build muscle.  His study was based on the idea of gene therapy: treating a disease caused by a mutated or malfunctioning gene by inserting copies of the normal gene into cells.  The cells essentially replace the non-functional gene with the normal one.  So, if you can use gene therapy to treat mutated genes, why can’t you use gene therapy to replace a “normal” athletic gene with a “high performance” athletic gene?

A review article by Dr. Craig Sharp that will be published in March, 2010, titled “The Human Genome and Sport, Including Epigenetics, Gene Doping, and Athleticogenomics,” discusses many athletic performance gene discoveries that may be possible targets for gene doping.   One example is a gene encoding myostatin, an inhibitor of muscle growth.  Exercise tears muscles, which results in increased expression of actin and myosin.  This increase in expression is eventually repressed by the protein myostatin, preventing excessive muscle growth.  In 2004, a boy was born with a mutated form of myostatin that disrupted some of the protein’s function.  The boy had significantly hypertrophied muscles, and was still unusually muscular at age 4.  Based on studies like this one, by injecting muscle cells with the mutated form of myostatin, Sharp believes that athletes and bodybuilders can create greater muscle mass than without the gene doping because inhibition of muscle production will be decreased following exercise.  Who knew genetic studies could lead to Schwarzenegger-sized people?

Death does not seem to scare overzealous coaches and athletes, who may bypass the risks of gene doping to achieve that extra edge.  In several gene therapy studies, some patients developed cancers or severe autoimmune responses to the product of the injected genes.  A 2008 report by Dr. E.B. Wheeldon showed that a patient went into an extreme immune response due to a reaction with a carrier virus used to transmit the gene of interest into his cells, causing death from organ failure.  This does not seem to discourage some athletes and coaches.

Have athletes started using gene doping to get ahead?  An experimental drug, Repoxygen, was developed to treat severe anemia due to a mutated gene.  As several Olympic coaches discovered, Repoxygen contained the gene for erythropoietin (EPO), which increases red blood cell production and performance.  EPO itself is a currently banned substance by WADA for performance enhancement—but how can one detect the gene for it?  There are no current established methods for gene doping detection aside from muscle biopsy, says Sharp, which is a painful and unappealing method of detecting changes in tissue development.  A rising technique commonly used in cancer genomics may be the key: DNA microarray.  A DNA microarray detects changes in gene expression in a person between two periods in time.  In order for anti-doping agencies to use this method in top competitions such as the Olympics, an athlete’s genetic file must be established as a reference.  WADA has already developed a “passport” program to keep blood and urine samples of athletes on file to use for future genomic comparisons.

Gene doping raises an ethical issue that surpasses steroid use due to its difficulty in detection, although gene doping has been banned for over 5 years for major competitions.  By the 2012 Summer Olympics in London, genetic testing could be a common procedure by anti-doping committees.  It seems that as we learn more about the way the body responds to exercise and why the world’s top athletes are so good, more daemons are unleashed from Pandora’s box.

How heart malfunctions function

By Justin Williams ’13

Calcineurin Enzyme

Heart disease is among the deadliest diseases in the world. Last year it was responsible for  631,636 deaths in the United States alone. For many years it has been known that the enzyme calcineurin plays a major role in heart function, but what exactly it did was not known until now. Just this week (February 19th), researchers at the Cincinnati Children’s Hospital Medical Center and the Howard Hughes Medical Institute published the results of their study, which shows that calcineurin plays a major role in regulating many vital functions of the heart.

In this study, the researchers observed the hearts of mice, manipulating the level of calcineurin in their systems. Their data shows that “calcineurin in hearts of mice is directly linked to proper cardiac muscle contraction, rhythm and maintenance of heart activity.” When mice were almost completely stripped of calcineurin they displayed major heart problems which included “heart arrhythmia, failure and death” said Dr. Marjorie Maillet, one of the leading investigators in the study.

Prior to this, calcium has also been identified as necessary for a healthy heart. In this study, in addition to the aforementioned results, researchers found that the mice who were bred with a calcineurin deficiency displayed a severe reduction in the expression of these calcium related genes. Using this newfound link they have proposed a “feed-forward” mechanism, hypothesizing that when the calcineurin is activated by calcium, the effects of calcineurin on the heart will be increased.

While there are some drawbacks to this study, mainly that it is the first of it’s kind and was performed on mice, the results are still promising. Dr. Maillet certainly thinks so, saying that it “offers important insights for future studies that could lead to new approaches in diagnosis and treatment of heart patients.” It is still a little early to call, but things are starting to look up in the world of heart disease.

The original article can be found here.

Enterprise will “pick you up” in cleaner burning buses

By Amy Woolf

Enterprise Rent a Car company leads the way toward the incorporation of cleaner burning fuels into its fleet of cars. Over the next five years, the company is going to convert its entire shuttle bus fleet to B20, a 20 percent biodiesel mixture. It has already converted its fleets that are in high profile, metropolitan areas like Detroit, Los Angeles, Boston and Chicago.

Enterprise Holdings has the biggest fleet of buses, cars, and trucks in the world today. It is the only rental car company that is investment-grade. It has the potential to pave the way for equal companies to adopt the use of cleaner fuels. It is important for powerful companies to pursue environmental protection initiatives because they are also usually the biggest culprits of environmental harm.

Enterprise is following the goal set forth by the U.S. Environmental Protection Agency to have renewable fuel use at an average 36 billion gallons by 2022. The EPA also requires that 1.15 gallons of biodiesel be used in the US by the end of 2010, because biodiesel has the best environmental track record of any other mass-produced renewable fuel.

Biodiesel is a clean burning fuel that is able to be made from fresh or used vegetable oil, and can also be derived from animal fats and plant oils. B20, 20 percent biodiesel mixed with petroleum, can be used in any diesel engine without any modifications being made to the engine.

For more information about Enterprise Holdings environmental commitment, visit this site

Press Release

Drugs That Kill Bacteria Can Also Make Them Stronger

By Johnathan Nieves ‘11

A recent study showed that exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug under development by Radnor, PA-based PolyMedix, Inc. shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.

Click on the Image above to see Polymedix's Drug In Action (Sources: Image, World Health Organization; Video, Polymedix, Inc. )

If you don’t take your prescription antibiotics as your doctor advises, then listen up. Just last week (February 12) a paper published in the journal Molecular Cell described how exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug currently under development by Radnor, PA-based PolyMedix, Inc., however, shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.

Drug resistance has been a growing health concern for decades now since the introduction of penicillin in the 1940s, the first available antibiotic of its kind. Drug resistance occurs because of bacteria’s natural ability to evolve through mutations it incurs as it reproduces. As it turns out, researchers have found that low antibiotic dosages are triggers for increasing the rate at which bacteria mutate, thus, increasing the likelihood of drug resistance.

“Like anything in nature, bacteria have ways to fight its opponents, and do so either by pumping antibiotics out of themselves through a process called efflux, or by rapidly mutating and changing the shape of the target of attack of the antibiotic drug. They can do this, even with large doses of antibiotics, it’s their innate way to try to survive,” explains Bozena Korczak, Vice President of Drug Development at PolyMedix Inc..”

“Upping the antibiotic dosage may be a viable solution but not the ultimate one,” adds Korczak. Driven by science conducted at the University of Pennsylvania, PolyMedix is investigating a new type of antibiotic drug that works by imitating the human immune system.

PolyMedix’s investigational antibiotic agent, called PMX-30063, is the first of its kind with a new approach to address the serious health implications of drug resistance by mimicking host defense protiens. Unlike most antibiotics, host defense proteins work fundamentally different. Rather than crossing the bacterial membrane to find a target like most antibiotics, they selectively target the cell membranes integrity by poking holes into it. This diminishes the bacteria’s ability to remain intact and the bacteria and its internal components become degraded (See video demonstration by clicking on the image above).

Polymedix purports that this unique mechanism of action makes drug resistance unlikely to develop. Korczak insists that “the best approach to preventing this phenomenon is by directly attacking the bacteria’s cell membrane, rendering them destroyed and dead in a way that there is little chance of resistance.”

To study the ability of bacteria to resist an antibiotic drug, a laboratory experimental method known as “serial passage” is used by intentionally trying to create bacterial drug resistance. Using this experiment, PolyMedix has shown that resistance did not appear to its compounds in contrast to traditional antibiotics.

So far, data from two Phase I clinical studies demonstrate that the compound is safe and well-tolerated. PolyMedix is on schedule to complete the third and final segment of the ongoing Phase 1 study with PMX-30063 early this year and commence Phase 2 studies later this year.

PolyMedix has received 9 grants and research contracts from the National Institutes of Health and branches of the military to help support the development of its antibiotic compounds.

To view the press release associated with this piece, please click here.

To learn more about PolyMedix, Inc., please visit www.polymedix.com.