genetics – Writing Science News

Change Your Mind: How Stress Reshapes Your Brain

By Kelly Lohr

It has been known for a while that too much stress can be bad for your health. A new study now shows that it can affect your brain too. Research through a collaboration between Rockefeller University and Cornell University suggests that stress can been linked to harmful changes in some brain structures. Sometimes these brain changes can be advantageous, such as making new synaptic connections to remember and learn from a stressful, life-threatening event. However, some changes can be detrimental.

g001098 — A mouse hippocampus labeled with NeuroTrace® green fluorescent Nissl stain

The project has identified a protein possibly involved in remodeling the brain under stress. It was found that the brains of mice lacking the protein called brain-derived neurotrophic factor (BDNF) look like the brains of stressed mice. The study examined changes in the neurons of the hippocampus, a brain area important in memory, mood, and cognition. When normal mice were stressed through confinement to a small space, the tiny projections on their neurons called dendrites retracted in the hippocampus. The hippocampus itself was also reduced in overall volume. The study compared these mice to other mice that were missing a copy of the gene that produces BDNF. It was found that these genetically-altered mice had brains resembling those of stressed mice.

Not only does this finding show that stress can produce brain changes. Bruce McEwan of Rockefeller University suggested that BDNF also may be “one of the proteins that play a role in mediating the brain’s plasticity.” This holds promise for a better understanding of the role of neuronal remodeling in the hippocampus and its importance in memory and emotion.

Written April 13, 2010

For more information, visit http://www3.interscience.wiley.com/journal/123249229/abstract?CRETRY=1&SRETRY=0.

A Fungus with a Deadly Sweet Tooth

By: Kristen Kocher

This is your brain on Cryptococcus — severe brain swelling caused by a Cryptococcal infection

As it turns out, humans aren’t the only ones with a sweet tooth. According to an article published last week (April 5, 2010) in mBio online microbiology journal, a certain species of fungus, Cryptococcus, were found to thrive and reproduce through consumption of a sugar, inositol, which is commonly found in the human brain and spinal cord.

Joseph Heitman, M.D. and Ph.D. and his team of researchers who have been studying Cryptococcus at the Duke Department of Molecular Research believe they have identified a set of almost a dozen genes that code for sugar transport molecules. Sugar transport molecules are important in borrowing sugars from parts of the body to use where they are needed. Normal fungi have only two genes that code for these sugar transport molecules. It is therefore hypothesized that because of the increased number of genes coding for sugar transport molecules in Cryptococcus, this fungus is able to more quickly gather sugars to consume. According to Heitman, “Inositol is abundant in the human brain and in the fluid that bathes it (cerebral spinal fluid), which may be why this fungus has a predilection to infect the brain and cause meningitis. It has the machinery to efficiently move sugar molecules inside of its cells and thrive.” Meningitis is a serious health problem that involves the swelling of the area around the brain, causing a build up of fluid, which can have negative effects on brain function. Meningitis is a medical emergency because it occurs quickly and often results in permanent brain damage or death.

Before it was able to infect the brain, it is believed that Cryptococcus originally localized itself on plants. Plants are rich in inositol and most likely caused Cryptococcus to adapt and change its genome to produce more sugar transport molecules in order to survive and replicate. Because the brain and spinal cord naturally have very high concentrations of inositol it makes sense that Cryptococcus would target the brain as a niche.

Furthermore, it has been found that inositol stimulates sexual reproduction in Cryptococcus, so in areas of plentiful inositol concentrations, such as the brain, reproduction occurs often and rapidly.

Chaoyang Xue, Ph.D., formerly a postdoctoral research associate in the Heitman lab and now an assistant professor at the Public Health Research Institute at the University of Medicine and Dentistry of New Jersey, comments, “A connection between the high concentration of free inositol and fungal infection in the human brain is suggested by our studies. Establishing such a connection could open up a new way to control this deadly fungus.”

While Cryptococcus’ love for sugar may seem only beneficial, it turns out that because the fungus relies so heavily on inositol for nutrition, scientists have found a way to essentially put the fungus on an “Atkin’s-esque low-carb diet”. This “diet” would greatly reduce the ability of Cryptococcus to multiply, thus lessening its effects on the human brain.

Original Press Release

Check out mBio online microbiology journal for more articles and other information on this research.

Click here information on the Heitman lab

A Truly Sweet Deal

By: Kristen Kocher

Today, geneticists at Cold Spring Harbor Laboratory (CSHL) in New York and their colleagues at Hebrew University in Israel published a recent study about a genetic mutation in tomato plants. According to their research, a gene, called the florigen gene, has been isolated that has the ability to boost the yielding potential of tomato plants and controls when a plant matures and flowers. The harnessing of this gene is incredibly beneficial because it works in a variety of tomato plant species and across a range of environmental conditions.

So, why is this a sweet deal for farmers? Well, the gene would give farmers the ability to grow tomato plants year-round, greatly increasing the income of money of the agricultural market. Head researcher at CSHL, Zach Lippman, Ph.D, notes, “This discovery has potential to have a significant impact on both the billion-dollar tomato industry, as well as agricultural practices designed to get the most yield from other flowering crops.” To make this deal extra sweet, this gene also enhances the taste of the tomato, making it sweeter and more palatable than normal tomatoes. Normal, non-genetically modified tomato plants produce a limited amount of sugar that they equally distribute to their fruits. With the florigen gene, the amount of sugar produced in tomato plants increases, thus making the fruit produced sweeter and better tasting overall.

The discovery of the florigen gene came when the team at CSHL was searching for genes that initiate increased yield, or hybrid vigor. Hybrid vigor, or heterosis, is a breeding process in which two plants of different varieties are crossed to produce hybrid offspring with higher yields. Charles Darwin discovered heterosis over a century ago through the study of corn and rice crops. The CSHL lab team recently rediscovered heterosis and while the mechanism is largely still unknown, their research has provided some clues as to what the mechanism may be. According to their findings, this phenomenon occurs due to a single gene that when present causes something called, “superdominance.”

The CSHL team tested many varieties of plant to identify if the florigen gene was superdominant, or always expressed when present. They catalogued a collection of 5,000 tomato plants and located single gene mutations that affect certain characteristics of the plant, such as fruit size and leaf shape. In this mutant library they noticed a trend among 60% of the plants that found a certain gene, the florigen gene, causes increased yield. According to a breakthrough publication in 2005, the florigen gene codes for the production of a certain protein, florigen, which is associated with the timing of maturation and flowering.

They believe that in tomato plants there is a delicate balance between the production of the florigen protein and another protein that controls plant development. Maturation, the 60% trend seen in tomato plants with a single gene mutation, still occurs when a single copy of the florigen gene is present, thus suggesting that it may have heterosis properties.

In the future, geneticists working on harnessing heterosis and improving crop yield have planned on researching the effects of the single gene mutation more fully. Lippman comments, “Mutant plants are usually thrown away because of the notion that mutations would have negative effects on growth… our results indicate that breeding with hybrid mutations could prove to be a powerful new way to increase yields, not only in tomato, but all crops.”

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Original Press Release

The Sea Squirt: An Answer to Alzheimer’s?

Ciona_intestinalis2 — Ciona intestinalis

By Kelly Lohr

The newest breakthrough in Alzheimer’s research is coming from an unlikely source–a sea squirt. Just this week (March 2, 2010) Mike Virata and Bob Zeller of San Diego State University believe that Ciona intestinalis, known commonly as the sea squirt, may be the perfect model organism for this disease.

The brains of Alzheimer’s patients are typically filled with tangles and plaques made of the protein fragment beta-amyloid. Alzheimer’s disease affects nearly 4 million Americans and an estimated 27 million people worldwide. It is the most common form of age-related dementia and has no cure. Current drug regimens only relieve symptoms and cannot halt the progression of the disease. Research in the scientific community is currently aimed at slowing the disease through drugs such as Aricept and Namenda which are focused on decreasing plaque accumulation.

Recently, research has shown the need for an improved model organism to aid in understanding the pathology of the disease. Currently, genetically modified strains of mice have been the organism of choice in the research of this disease. However, there are limitations in the use of mice including an extremely long waiting period for plaque development like those seen in Alzheimer’s brains. Also, these mice do not contain the same genetic mutations linked to hereditary risk of Alzheimer’s disease. Mice are also more costly to purchase and maintain for research.

Sea squirts are tunicates, marine organisms with a hard outer tunic and a soft body. They live on underwater structures and are filter feeders that eat small plant material. It has been suggested that sea squirts are actually our closest invertebrate relatives. As far as research benefits, sea squirts share nearly 80% of our genes and resemble vertebrates in their immature form. These animals are inexpensive to house and contain all of the genes needed for the development of Alzheimer’s plaques in humans.

Virata and Zeller found that by giving the immature sea squirt amyloid precursor protein, a mutant protein linked to hereditary Alzheimer’s, sea squirts developed brain plaques in a single day. Further, these plaques and the behavioral deficits seen in these animals were able to be reversed using a drug meant to remove plaques. Such techniques have been ineffective in all other invertebrate models, including the commonly used nematode, C. elegans. Now, investigators can be freed from genetic, time, and financial constraints. These findings provide a resource for an entirely new take on Alzheimer’s research…all because of a sea squirt.

For more information, click here.

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 days of the flying mosquito may be drawing to a close. In a study published in the February 22^nd 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

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.

Running in Genes

By Abby Larson

Can someone really be born to be an athlete? Science says so. The idea of a genetic basis to exercise is a fairly new area of science, but it makes sense based on how the human body works. The expression of genes controls the function of human physiology: muscle development, capillary growth, hemoglobin concentration in red blood cells, etc. After strenuous exercise, gene expression fires up to control muscle tissue repair due to increased forces on the body and tissue metabolic demand. Capillaries feeding the muscles grow and become more efficient at delivering oxygen to tissues. All of this is controlled by gene expression, the cellular switchboard of the human body.

Recent studies have identified over 200 genes that can determine the body’s ability to adapt quickly to exercise. Based on this, training and conditioning could only take an athlete up to his or her genetically predetermined potential. Does this mean that children can be genetically tested to see if they will be good at sports? Is there a gene that makes a good football player versus a good runner? It’s more complicated than saying if a person has a specific gene, he or she can be a top athlete. Like all processes in the human body, multiple genes are involved in adaptation to exercise and gene interactions play a large role. Gene products don’t interact in a linear fashion, but in pathways and networks. This makes genes harder to understand, and our knowledge of the interactions is in its infancy. Once these pathways are discovered, scientists can begin to understand the extent to genetic determination of athletic ability.

These studies on the genetic basis of exercise are not going to benefit just athletes—physical activity is one of the greatest preventative medicines for obesity, diabetes, and heart disease. It is likely that genes correlated with exercise response could be mutated in people that have obesity or heart disease, which proposes new options of drug and gene therapy as preventative medicine. The more we understand the benefits and mechanisms of exercise, the better we can understand how exercise can be used to improve public health. So next time you go to the gym or run outside, think to yourself, “this is science.”

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Not Your Average Fairytale

By Kristen Kocher February 4, 2010

Numerous genetic diseases, especially hereditary brain diseases, are untreatable therefore subjecting many individuals to a life of endless pain and suffering. However, in recent years with the development of the technique of gene therapy, new hope has been brought to life in those diagnosed as “terminally ill” with the promise of the “happily ever after” ending that everyone deserves.

Gene therapy is still not used as a mainstream medical technique because much of the process is still in the developmental stages. Recently, geneticists have been desperately working to perfect the successful transport of therapy genes into brain cells. In many cases, the diseases are caused by a single gene or protein mutation but can cause devastating affects, which normally result in the loss of brain cells and fatality.

A recent scientific breakthrough has finally made it possible for therapy genes to be inserted into brain cells and cure certain genetic diseases. Before this discovery, therapy genes were only administered through the use of viruses, predominantly the herpes virus, HSV-1. While HSV-1 has the ability to effectively transport large genes into the nucleus of the targeted cells, once the genetic information enters the nucleus it is unable to be integrated into the mammalian, host genome. This proves to be unhelpful as the therapeutic information is quickly silenced and within a few days the effects of gene therapy are no longer visible.

Another molecule used for gene therapy transport is known as “Sleeping Beauty”. The aforementioned molecule is named as such because it is innately a silent gene that was activated, or “awakened”, by scientists. The discovery of this molecule is beneficial because it has the ability to take the target gene intended for therapy into the nucleus and integrate it directly into the mammalian genome. The genes transported by Sleeping Beauty, however, must be relatively small, roughly 15 to 30 times less than the amount of DNA carried by HSV-1. This is unfortunate because the genes that are used for treatment of diseased brain cells are predominately large and cannot be carried by Sleeping Beauty.

So, where does the happy ending come in? These two molecules individually have characteristics that make them useful in therapy gene transport but separately cannot aid in the treatment of brain disease. However, thanks to the research of William Bowers, Ph.D. and graduate student Suresh de Silva, this blockade has been removed. With the creation of a hybrid molecule made up of both HSV-1 and Sleeping Beauty, geneticists have been able to successfully integrate large therapy genes into the mammalian genome, which, though current experiments, have resulted in long-term therapeutic gene expression. The creation of this hybrid therapy gene transport molecule promises a bright future and “happy ending” for those suffering from terminal, genetic disease.

Original Press Release

Find out more about the projects going on in Bowers Laboratory