A Fungus with a Deadly Sweet Tooth

By: Kristen Kocher

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

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

Uncovering a Missing Piece to the Puzzle

by Kristen Kocher

Researchers at the University of Edinburgh, have recently uncovered that the behavioral disorder, autism, is linked to abnormal brain development caused by Fragile X syndrome. Providing a critical clue into this puzzling disease, this research has begun to demystify the complexities of autism.

To begin unlocking the mysteries of autism, Professor Peter Kind at the University of Edinburgh, began research in an attempt to locate the differences between a normal brain and a brain with Fragile X. Through the use of a mouse model, certain sensory regions of the brain were found to react differently to stimuli, such as touch. Kind and his team believe that these differences may be found in other regions of the brain, which would aid in explaining the effects of Fragile X in patients. This discrepancy, it was also found, is caused by certain irregularities in brain development caused by the Fragile X mutation. Further studies by Kind and his associates also showed that abnormal brain development occurs during development in the womb. The identification of this window of time in which autistic brain development occurs may provide a more tangible and effective option for treatment methods to combat the disease.

Fragile X syndrome affects approximately one in every 4,000 males and one in every 8,000 females around the world and is the leading cause of autism. In terms of genetics, Fragile X is caused by a mutation within a gene sequence of the X chromosome. Autism presents itself in early childhood and is usually identified in a child that slow speak and does not interact with others. Compulsive, ritualistic, self-injury behavior are also characteristic of autism. As a result, this condition severely inhibits an affected individual’s ability to communicate with the outside world, causing numerous social, language and behavioral problems.

In the past, autism has proved difficult to study because it affects the inner workings of the brain without having any visible pathogenesis. In addition, those affected by Fragile X/autism are unable to reveal hints about the disease because they are unable to communicate with others. Therefore, without a fundamental understanding of the disease, treatment and therapy options are extremely limited, making autism a frustrating condition for the individual, the family, and the doctor. However, thanks to the research of Professor Kind and his team, the autism puzzle is one piece closer to being solved.

Original Press Release

Act Early, Spread Awareness

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

Kristen Michelle Kocher

Kristen is a sophomore Biochemistry and Molecular Biology major at Dickinson College. She’s from Philadelphia, Pennsylvania. On campus, she’s involved with community service and Delta Nu sorority. During the summer of 2009, she worked as a research assistant in the neuroscience department at Drexel University College of Medicine doing research for ALS.