RicochetScience Goes Twittering

The sign of a true geek is their desire to try out new tech - after all, new e-toys are like crack to a geek... and I am no exception. Although I have been a little slow in seeing the benefits of Twitter, I am beginning to come around. At first I thought that it might just be the next generation of social text messages, but now I am starting to see it in a new light - a new form of scientific communication.

Although I will always be a geneticist at heart, my research interests now focus on how to effectively communicate information quickly to students and interest groups. Obviously blogs are a component of that communication, but I also am experimenting with eBooks, Kindle, Nings, and Wiggios (these are for textbook development mostly). RicochetScience is already on Facebook.... and I am sure that there is more to come.

So if you have an interest in following some of the latest developments in science, with a strong focus on genetics, then go ahead and subscribe to my twitter post, RicochetScience. At least once a week I will send out posts about some of the more interesting stories in the news, and maybe a few links back to this site as well. Please feel free to email me at any time about your comments, good or bad - feedback is important!

And I promise you... you won't have to read any posts about what I am doing right now...

Genetics Community Online

Nature Publishing Group has just released a new genetics education website called Scitable. It represents a new generation of making science content and experts available to undergraduate students and the general public. My first impression of this is that it is pretty impressive. Community-based learning is widely recognized as an effective learning strategy, and it will be interesting to see how scientists, students, and the general public react to Scitable.

For more on the potential uses of Scitable for developing a genetics community - see my column on ScientificBlogging.com. For now, check out the site and let me know what you think. Should this be the way that education is addressed in the future?

Links for Scitable were repaired on January 23rd

Book Review: What is Life?

Anyone who has taken introductory biology is familiar with the stories of Mendel, the discovery of DNA, and Charles Darwin's adventures with evolution and natural selection. What most of these people probably do not realize is why this material is relevant in the modern age of molecular biology.


Ed Regis's book What is Life? Investigating the Nature of Life in the Age of Synthetic Biology takes the reader on the journey from the 1943, and the publication of Erin Schrodinger's What is Life? to the labs of modern day biochemists, cell biologists, and geneticists, who are beginning to unravel some of the fundamental questions about life. The book explores how we, as scientists, have reached the ability to develop life in the lab. This is often called synthetic biology, and it is frequently thought of as being the stuff of science fiction. Several of my blogs have covered topics relating to synthetic life (for example, see Synthetic Life Makes Synthetic Proteins), most because this is going to be a hot topic for society in the next few years. For as Ed Regis points out in his book, the work is already underway, and scientists are getting closer to unlocking some of the secrets of what it means to be "alive".

For those students who are burdened with a heavy reading load, or those non-students with hectic lives, this book is a mere 171 pages in length. Better yet, it is written in a non-technical style that brings to life many of the historical people in the study of the life sciences. It is an easy read, and anyone who has an interest in understanding science should check out this book.

The Death of Junk DNA and Birth of the Junkome

Not so long ago, geneticists considered the vast stretches of non-coding regions in DNA to be “junk,” nothing more than the remnants of our evolutionary history. If it wasn’t a traditional gene, and didn’t produce a protein, it wasn’t of interest to most scientists. Luckily, not everyone considered these regions of DNA to be junk. Some considered the junk DNA to be the dark matter of the genome. They believed that it must have some function, but no one had yet determined exactly what that function was.

One of these individuals is Dr Craig Pikaard at Washington University- St Louis. His research group has discovered another use of junk DNA – it acts as a component of the cellular immune system by enhancing the ability of the cell to combat infection by viruses and transposons (also known as “jumping genes”). In a recent manuscript published in the journal Cell (vol 135 #4) Pikaard and associates demonstrate that in Arabidopsis , the fruit fly of plant genetics, the RNA polymerases within the cell use these non-coding regions of DNA to silence viruses and transposons. RNA polymerases are normally active in the process of transcription – the first stage of gene expression. Pikaard’s work suggests that these regions of “junk” DNA may be important in the generation of small interfering RNAs, so siRNAs. siRNAs are known to be involved in the silencing of genes by interfering with the transcription process. The medical community is very interested in the use of siRNAs in the prevention and treatment of diseases. Pikaard’s discovery in Arabidopsis should pave the way for additional studies in animals.

It seems that the time has come to let the term “junk DNA” fade into obscurity. In its place lets use the term “junkome” – those regions of DNA that we have no idea what they do, but agree that they must do something. After all, assuming something does not have a function because we do not understand what it does is not a lesson that we should be teaching young scientists.

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WUSTL news release

The Battle Against Viruses Heats Up

Viruses are nasty opponents, as anyone who has followed the battles against influenza, SARs and HIV/AIDS can attest. They are diverse and in many cases evolve at rates that confound efforts to contain them. Anyone who has gotten a flu shot, and then came down with the flu a few months later because the “strain” of virus that the vaccine was not the same as the “strain” that they were infected with, knows just how fast viruses can evolve. In many cases, medical professional never really know which virus has caused the symptoms in their patients, and this complicates treatment and often leads to the misuse of antibiotics, which, of course, are never effective against viruses.

At the ScienceWriters 2008 New Horizons in Science meeting at Stanford University (sponsored by CASW) this week, Dr. Joseph DeRisi of UCSF presented an interesting talk on his research to develop a new form of “chip” as a diagnostic tool for identifying the viral contributions to diseases. Gene chips are often used by molecular biologists to determine the relationship between a gene and an observed condition. Dr DeRisi's work takes this approach one step further.

What is interesting here is Dr. DeRisi’s application of evolutionary genomics to his work. Like microbiologists, virologists recognize that they have only identified a small fraction of the diversity of viruses that are out there in the natural world. Despite advances in sequencing technology, the ability to sequence every virus in a given environment, such as a fecal or nasal sample, is still not cost effective. However, what Dr DeRisi has done is to develop a “viral chip” that contains not the entire sequences of every virus, but rather the sequences of key genes that are evolutionarily important to certain families of viruses. When one of these viral chips is exposed to a sample, a computer program determines the level of similarity between the DNA (or RNA) in a virus and the sequence on the chip. For previously unknown viruses, this can allow a quick classification of the virus to a certain group, and has been proven to be very successful by Dr. DeRisi’s team in diagnosing diseases for which no known cause could be determined by diagnostic tools.

Furthermore, Dr DeRisi has proposed making these chips available at cost to the medical community through a non-profit organization. The availability of a new technology at an inexpensive cost would represent an important new development in the war against viruses, and would rapidly generate an increase in data for public health officials.

Additional Links

DeRisi Lab at UCSF

Synthetic Life Makes Synthetic Proteins

The genetic code is the metabolic instructions by which the genetic information in the DNA is translated into a protein. The fact that almost all organisms use the same code is prime evidence that all life is related in its evolutionary past. The code is considered to be "conserved" and "universal". Of course, the concept of universality may be challenged by exobiology's explorations of Mars, Europa, and Titan, but the conservative nature of the genetic code, with the exception of a few Archaebacteria, has always been a cornerstone of biological science.


But the reality of course is that the Genetic Code is like the Cobal language of computer science. The Genetic Code is old (over 3.5 billion years). Of course life on this planet is not going to update the genetic code anytime soon - it is thriving using the old code, but evolution is a weird thing, if something better comes along, and a mechanism to adapt to that change exists, the out with the old and in with the new. Until recently it appeared to be metabolically impossible to "update" the code. But one species, Homo sapiens, may have discovered a way to fast-track the process.

The basic tenants of the genetic code is that the information coming from the DNA, in the form of messenger RNA, is "read" by a ribosome three units (also called a codon) at a time. Each codon codes for an amino acid, the building blocks of a protein. Proteins are the workhorses of the cell - everything depends on them. In other words, genes code for proteins. While we have had the ability to change genes for some time, using recombinant DNA technology and genetic engineering, until recently we were always confined to the use of the same old programming language.

Earlier this year, independent teams of researchers at Harvard University and the University of Cambridge have found ways to alter not only the genetic code, but also the cellular machinery responsible for deciphering the code - the ribosome. (see Synthetic biology: Rewriting the code for life by Linda Geddes, 2008). This process is called synthetic biology, and due to the efforts of biotech giants such as Craig Venter, this is no longer science fiction. We now have at our fingertips the technology to create new forms of life that are designed for specific missions and environments.

These advances open up unbelievable possibilities, and the potential for unimaginable nightmares. It may soon be possible to manufacture proteins that were not possible from a biochemical perspective just a few years ago. This could create new drugs that could finally eradicate some of our specie's biggest problems, such as cancer and HIV. It could also allow us to develop plants that tolerate salt water, or grow on toxic waste. A new programming language means endless possibilities. It also could spell our demise as a species. After all, the evolutionary history of life on this planet tells us that if something better comes along, the old is replaced... even if it is us. Let us not be so egocentric to think that we are special from an evolutionary perspective. Unless of course, you believe that our purpose on Earth is to generate our own successors.

My Friend, E. coli

While as a geneticist my vote would go to Drosophila melanogaster as the greatest organism of all time, I do recognize that Escherichia coli is probably one of the most beloved organisms of the biomedical research community. This versatile little microbe can be found in teaching and research labs from high schools to research institutions and large biomedical facilities. We probably know more about E. coli than almost any other organism on the planet, including ourselves. Many of the advances in medicine and drug development would probably not be possible if it were not for this wonderfully versatile little bacteria. But, as we are all aware, E. coli has a dark side.

The March 24 issue of New Scientist features an article ("Mystery Food Poisoning Traced to Salads") which presents statistics on the increase in the rate of food poisoning associated with salad greens. While the article does not specifically mention E. coli, if you asked the common person on the street what was causing the food poisoning in spinach and lettuce, most would guess this bacterium. In fact, E. coli is probably the only microbe, or any other organism for that matter, that most people know by its scientific name! Unfortunately, that recognition is not a good one. From baby diapers and water parks in the 1990s to ground beef and salad greens in this decade, E. coli has earned a reputation as a menace.

I have found that most students are surprised to find out that their intestines contain more bacterial cells than there are human cells in their bodies. Most are disgusted by the thought, and some actually pale when I mention that one of the leading organisms is E. coli. I have even had a few ask if they can get antibiotics from the campus health clinic to rid them of these "parasites."

After a brief discussion of why these little creatures are present in our system, and the benefits that they provide us by protecting us from harmful bacteria, synthesizing necessary vitamins, and stabilizing our blood glucose levels, most of the students develop a real appreciation for E. coli. From that point we can proceed to discussions on how important it is to keep your intestinal bacteria content by reducing unnecessary use of antibiotics and consuming plenty of fiber. It is then relatively easy to understand why probiotics, such as yogurt and Acidophilus pills, work as supplements. With a little public relations work, E. coli is transformed from the villain to a misunderstood hero.

Why is any of this important? In the March 1 edition of Science News, science writer Janet Raloff ("Nurturing Our Microbes") presents an intriguing possibility that someday it may be possible to reprogram our natural flora of microbes to combat disease. She first discusses how probiotic supplements may be used to increase the efficiency of intestinal bacteria in enhancing our immune system, by increasing the absorption of nutrients such as calcium and by regulating weight. Raloff then presents comments by Jeremy Nicholson of the Imperial College in London, who said that future drug therapies might one day be directed at the bacterial inhabitants of the intestinal system.

As a researcher, I think that is an important advance for medicine. We all know of the problems that have plagued large-scale implementation of gene therapy. Given the number of bacteria in the lumen of the gut, it should be possible to achieve a higher rate of transformation than is experienced in in vivo eukaryotic cells. Furthermore, by having the bacteria produce the drug of interest, it may be easier to get the drug directly into the bloodstream than traditional oral routes that need to navigate the hostile environment of the stomach.

And since this is an election year, and at least some of the focus appears to be on health care, the use of genetically modified E. coli may reduce the cost of certain medicines, since once transformed the individual would have a constant, renewable source of the drug.

However, before we proceed with the development of drug-producing recombinant bacteria, I would like to make a suggestion. If the drug companies state that they are ready to produce a genetically altered bacterium, especially one named E. coli, the general public is going to have a revolt.

Movies such as I Am Legend have not presented a pretty picture of genetically engineered organisms. Recent public responses to cloned meat, and once again to certain forms of immunizations, reveal that the general public is not convinced that we know what we are doing.

So my suggestion is this — start a public relations campaign on behalf of E. coli. Get E. coli, or its agent, on The Daily Show and Good Morning America. Start thinking about how to spin the benefits of E. coli to an increasingly research-phobic public. Work the media, begin ad campaigns, and most importantly, get the message out to the science teachers to incorporate it into their curriculum. For if we don't, this promising medical advance may be a tremendous waste of money.

Note: this article first appeared in the April 10, 2008 issue of BioWorld Perspectives, and is reproduced here by permission of AHC Media, LLC

Autism in the News

Autism is once again in the news. In the past several weeks news agencies, such as CNN, have brought autism back into public thinking through coverage both on TV and the web. While the news network has done an adequate job of presenting the concerns of parents and the opinions of the scientists, they have done very little to present the basic scientific information about autism. From my perspective, most people are completely confused about autism. In the past, an autistic child was sometimes viewed as the fault of the parents, and in the current round of coverage the disease is sometimes being presented as a result of a medical community which prefers not to face the facts regarding vaccinations. Neither of which is really true. Instead, we need to recognize that autism is a very complicated disorder – and that complicated disorders can take some time to sort out.

First of all, and probably most importantly, autism is most likely not a single disease. Like Alzheimer’s disease and cancer, autism is a term that we have adapted to explain a related group of symptoms, in this case severe communication disorders. Alzheimer’s researchers now distinguish their disease using terms such as “late-onset” and “early-onset”. We need the same approach for autism. We need to develop a common set of classifications for the disease so that we all know what type of autism we are talking about. And these classifications need to be easily understood by the news organizations and general public. No scientific techno-babble please! For those who are trying to understand autism, we need to be able to distinguish the various forms so that we know if the news and the scientific community is talking about a common form or a rare form. Also, since autism is not a single disease, we can’t expect that the disease is caused by the same factors in each case. Which leads me to the second important point – genetics.

Autism is probably what geneticists call a multifactorial, or complex, disorder. What this means is not only is genetics involved, but also environmental factors. Those environmental factors are without doubt chemicals. While the news has been focusing on thimerosal, a chemical additive that was used in many vaccines, the truth is that we live in an increasingly chemical world. Some scientists estimate that we come in contact with over 70,000 man-made chemicals over the course of our lives. We have no idea how many of these chemicals interact with each other. In other words, our cells, and especially the easily influenced cells of a developing child’s nervous system, are being bombarded with a potentially hostile array of chemical compounds. Now, back to the genetics. Many of our genes have minor variations that go unnoticed until the cell is placed in a certain environmental condition. So say for gene X there are 2 variants, lets call them X-1 and X-2. When X-1 is exposed to a certain chemical cocktail, the gene continues to function normally. But when X-2 is exposed to the same group of chemicals, the environment alters the way the gene works, called gene expression by scientists, producing slight changes in the cells. In a complex trait it may be necessary to have many of these gene variants, say X-1, Y-4 and Z-2 acting at the same time to produce a disorder. Sorting out multifactorial complex traits takes time and patience by the scientific community.

So what can we do? As parents and concerned individuals we need to aggressively lobby our elected officials to increase funding to not only study this disease, but to make life better for the increasing number of kids who are being diagnosed with autism. In addition to long-term studies of people with autism, we need to start enrolling pregnant mothers in prenatal studies that examine everything from the genetics of the parents to the types of chemicals that the mother comes into contact with during her pregnancy. Only then will we be able to provide some real answers on what is causing autism, and maybe develop a means of reducing its impact on future generations.

New Hope for Short People???

"Tall people have tall children, and short people have short children." For many this statement summarizes all that needs to be known regarding the relationship between a person’s height and heredity. For geneticists, however, these types of general observations represent an open intellectual challenge, since a more careful observation of the human population reveals that there is considerable variation with regards to height, and that it is possible for tall people to have short children, and vice versa.

A Quantitative And Multifactorial Trait

For years scientists have known that height is a quantitative trait, meaning that the population does not fall into distinct phenotypic classes. Anyone who purchases clothes knows that people are not "tall," "short" or "medium." Instead, height in humans is distributed around a mean value. This form of distribution, or bell-shaped curve, is characteristic of a trait that is under the influence of multiple genes, each one having an additive effect on the phenotype. The more of the
alleles that a person has, the further along the distribution the phenotype is located.

Geneticists also recognize that height is a multifactorial trait. Multifactorial does not mean simply that multiple genes are involved. The term multifactorial indicates that there are both genetic and environmental factors that are contributing to the observed phenotype.

A wonderful illustration of the multifactorial basis of human height is provided by Ricki Lewis in her textbook, Human Genetics, Seventh Edition. Lewis presents two photos of the graduating class of Connecticut Agricultural College, one taken circa 1920, the other in 1997. In both photos, the students were placed into phenotypic classes by height (to the nearest inch). The distribution of both classes follows a distinctive bell-shaped curve characteristic of a quantitative trait. The difference is that the mean height of the 1997 class was much greater than that of the 1920 class. Whereas the tallest individual in 1920 was 5’9", the tallest individual in 1997 was 6’5".

Since it is unlikely that a "tall" mutation has infiltrated the entire graduating class, and therefore the genetic basis of the two populations should be roughly the same, then there must be some other factor involved. Human geneticists and medical professionals say that the overall change in height over the past several decades is primarily due to improvements in human nutrition – an environmental factor. Building on this, geneticists have suggested that human height may be the
result of the interaction of environmental factors with several major genetic mechanisms and a host of minor genes.


Use Of Genome-Wide Association Studies

As a geneticist who has studied quantitative traits in Drosophila, I can testify that one of the hardest problems facing quantitative geneticists is the ability to tease out the influence of major and minor genes on a phenotype. Many methods exist to investigate the contributions of a single gene to a phenotype, but searching for all of the minor contributing genes has remained a relatively difficult task. Recently, a research group led by Timothy Frayling at Peninsula Medical School in Exeter, UK, reported the use of the genome-wide association studies (GWAs)
to identify genes responsible for variations in the height of humans (Nature Genetics, October 2007). The use of association studies in human genetic analysis is nothing new as they have been used with a variety of genetic markers for several decades. However, the use of GWAs in this manner is something significant as it allowed the researchers to look at contributing alleles across the genome, and not simply in the vicinity of candidate genes. This technique should give researchers the ability to identity a greater number of minor genes, or those that make smaller contributions to the phenotype in question. This could prove to be very useful for complex diseases and traits that are under the control of multiple genes.


Breakthroughs In HMGA2

The gene that Frayling’s group identified, HMGA2, is not a new discovery. As the researchers report, it has been known for some time that severe disruptions of this gene can cause drastic changes in the height phenotype (dwarfism and gigantism) of mice. What Frayling was able to show is that certain alleles of this gene are associated with height at specific times during development. Interestingly, the associations indicated that certain alleles are associated with an
increase in height between the ages of 7 and 11 years and persisting into adulthood. This identification of this temporal importance suggests that other genes remain to be identified that play a role earlier in life. But there is also a catch – the gene that is responsible for the added height is also associated with an increased risk of certain types of cancer. The gene product of HMGA2 belongs to a family of proteins that act as DNA-binding proteins, meaning that HMGA2 most likely has a role in the regulation of gene expression. Although HMGA2 is not an oncogene, it has been observed to be overexpressed in certain types of tumors, meaning that while a gene might be a minor gene in one quantitative trait, it may be a major gene for another trait.
With the developing promise of gene therapy might it be someday possible to prevent individuals from being vertically challenged? In today’s world there is always someone who will want to capitalize on a discovery such as this by promising increased height to short people. Though some might see it as an opportunity to change or select the phenotype of an individual, in reality this paper has a far greater significance. The identification of HMGA2’s role in height
is an important breakthrough in the study of complex quantitative traits, and it demonstrates the power of new genome analysis techniques that are coming online. As Frayling and his colleagues suggest, the true power of this technique will be when it is applied to the study of complex diseases.

This article was originally published in BioWorld Perspectives (vol 1 # 46) in November 2007 and is reprinted here by permission from AHC Media LLC.