After conducting a bacterial transformation lab with my students, where we genetically engineer the bacteria to make a jellyfish protein that fluoresces, we always jump into the discussion of why this technique is important.  I always try to get the students to think of ways that this could benefit them.    

Among other uses, we finally get to the idea that these bacterial cells can be used as factories to make any protein you want, even human proteins.  It all depends on what recipe, or gene, you give them.  If you give them the recipe to make human insulin, they will. And then this insulin can be used to treat diabetes. 

They can see the benefits when discussing bacteria, but once I show them a picture of a multicellular organism that has been engineered with this protein, such as a pig or monkey, the debate begins to heat up.  That while the protein is harmless to the organism, they don’t fell it is necessary to make pigs glow.  While this may be true, many researchers would beg to differ. 

Researchers use this protein in many studies that were once invisible.  If they are studying the production of a protein, maybe when the protein gets produced during development, or in what type of cell it gets made, they can visualize this process with the help of the green fluorescent protein.  This will hopefully give insight to many disorders that result from the faulty production of a protein.  We need to see how and when the process works normally to gain more information about when it does not work.  Then we can hopefully use this information to fix it.

Many debates arise during discussions involving genetic research because of the potential benefits that could arise from the study, while disturbing a few people or groups along the way.  These are good discussions to have with students though, as they may be faced with decisions in the future about potential career choices or matters that will affect them on a more personal level.

The initial goal of the Human Genome Project was to find, map and sequence all of the genes within the human genome.  Since the completion of the initial draft back in 2000, the White House predicted that this would lead to a new era of molecular medicine, bringing new ways to prevent, diagnose, treat and cure disease. 

It has been amazing to see what we have learned since then, but even more interesting to think of where this could go in the future.  Hopefully soon we will be able to apply this on a more individual basis, with people being able to identify potential risk factors for certain diseases at their primary care physician.  This then will lead to new developments for drug therapy, having a drug that will be able to target a certain pathway that is specific to that patient.  I can only wonder and look forward to what will come next.

Dr. Charles Arntzen (Co-Director of the Center for Infectious Diseases and Vaccinology, The Biodesign Institute and Florence Ely Nelson Presidential Chair, Arizona State University) has spearheaded the genetic modification of plants to enable food crops to produce antigenic proteins.  So far, he has experimented with bananas that protect against Norwalk Virus and potatoes that promote antibody production against Hepatitis B and pathogenic strains of E.coli.  Dr. Arntzen cautions that vaccine containing crops are medicines, not food that would show up at a local grocery store, and would be regulated as pharmaceuticals.  You can read an interview with Dr. Arntzen here.

Plant based, edible vaccines would not only make vaccine-aged children happier, they would also simplify global vaccine distribution. Currently, vaccines require refrigeration and skilled health workers to inject them.  Fruits and vegetables can be freeze dried and pulverized into powders that would be heat stable: vaccine powders and pills could then be shipped around the globe without concern for a “cold chain” to preserve them, and could be eaten by populations without access to trained health workers.

The US government has also acknowledged that plant based vaccines would be faster and cheaper to produce than conventional vaccines, which are made in eggs over the course of several months.  In early 2010, the research arm of the Department of Defense, the Defense Advanced Research Projects Agency (DARPA), awarded the Texas Plant-Expressed Vaccine Consortium a $40 million grant for Project Green Vax, an initiative to develop vaccines in tobacco plants.  The Project’s first task is to show that tobacco can yield 10 million effective doses of the H1N1 vaccine per month.  It would be incredibly ironic if tobacco redeems its reputation for being a public health scourge by becoming a public health staple.

One very amazing example of this is the Widowbirds that live in the grasslands of southern and eastern Africa.  During the non-mating season, the males and females look very similar to one another.  Once breeding season begins, the males molt and produce long black feathers, some that can be up to half a meter in length.  Studies have been done where feathers have been glued on to some males, and females chose these males over others with shorter tails.  You also have to wonder why the tails don’t get even longer.  That even though females desire very long tails, if they get too long, they could hinder the flight of the birds, which would decrease their fitness.    

Other examples that might be more familiar to you are the elaborate feathers of male peacocks, and the beautiful plumage of male birds.

One Scientist from Baylor College of Medicine in Houston Texas, Richard A. Gibbs, decided to test whole genome sequencing on his colleague, a medical geneticist, Dr. James R. Lupski, who suffers from a rare genetic disorder known as Charcot-Marie-Tooth Neuropathy (this disease damages nerves to the hands and feet and causes muscle weakness). As it turns out, this disease is caused by a single mutation in any of 39 genes. Dr. Lupski’s mutation turned out to be in a gene called SH3TC2. He inherited the mutated variant from both parents; however, the mutations were in different sites within the gene in each parent. His father had an error on one site, his mother in another. These mutations were also passed on to three of his seven siblings.

The second team, run by Leroy Hood and David J. Galas at the Institute for Systems Biology in Seattle WA, also decided to use Whole Genome Sequencing. They sequenced the genomes of a family of four, where two children each inherited rare, single gene diseases known as Miller Syndrome (this can cause malformation of facial features and limb development, but does not affect intelligence) and ciliary dyskinesia (this impairs the development of cilia in the respiratory tract and the fallopian tubes, which can lead to difficulties expelling mucus). The completed sequencing allowed the researchers to identify the genes causing these diseases.

Today, the cost of sequencing an entire genome has gone down quite a bit, from approximately $500 million to about $50,000. This technique has also allowed the Seattle scientists to estimate the number of mutations passed from mother to child, which turned out to be less than expected.

There are many diseases that are caused by a single, rare mutation in a gene. However, common diseases, such as cancer, may have mutations in many genes. This is what prompted the beginning of the Human Genome Project in 1987 at the cost of about $3 billion dollars.

After the project’s completion in 2003, scientists created a $100 million project called HapMap, which identified common mutations among human populations. This was meant to be a “short cut” to finding disease causing genes. As it turned out, about 2000 of these sites were linked to assorted diseases, but many more did not appear in working genes, implying that HapMap was somehow missing some of the connections between these mutations and diseases among individuals. Too much money was being spent, but not enough answers were being found.

Now some scientists lean toward the belief that common diseases do not have common mutations, but actually have rare mutations in multiple sites. Whole genome sequencing seems to be the “way to go” for gene and mutation analysis of diseases. The price for this type of sequencing is dropping as technology advances. In the near future, sequencing companies are hoping to get the price down to a $5000 genome.

Information for this blog was taken from:  http://www.nytimes.com/2010/03/11/health/research/11gene.html?hp

Undergraduate students are now being challenged during the International Genetically Engineered Machine (iGEM) competition at MIT to take this very common tool and apply it to a new field called Synthetic Biology. They can order different pieces of DNA to string together and function inside of living cells, almost like LEGO pieces being built up together to form a castle. There is actually a catalog of different types of gene segments, such as promoters, terminators and primers. Organizers of the competition are striving to go beyond simple gene transfer, by making new synthetic pieces of DNA that can be attached together to form a new set of instructions that can be taken up by a living cell, such as bacteria. Projects ranged from banana and wintergreen smelling bacteria, to an arsenic biosensor, to Bactoblood, and buoyant bacteria.

In a bone marrow transplant, a patient’s own marrow is destroyed and replaced with tissue from a donor. The donor marrow contains healthy hematopoietic stem cells (HSCs, adult stem cells in the blood) which repopulate the patient’s body with healthy red and white blood cells for oxygen transport and immune defense. Just as with other varieties of organ donation, tissue-type matches are critical. In the case of the AIDS patient, another screen was also applied: his doctors searched for donors whose cells were also resistant to HIV infection.

In order to infect a white blood cell, HIV must latch onto 2 receptors on the cell’s surface: the cd4 receptor and the CCR5 receptor. Some people have no CCR5 receptors due to mutations in the genes encoding the protein—those people are highly resistant to HIV infection. The AIDS patient received bone marrow from a donor whose HSCs (and subsequent white blood cells) could not produce the CCR5 receptor: his new cells cannot be infected by the HIV that decimated his old cells. The AIDS patient was, rather ironically, cured by receiving “defective” cells. The absence of a CCR5 receptor does not appear to affect normal physiology.

Bone marrow transplants are, unfortunately, not a feasible treatment option for the 33.4 million people infected with HIV worldwide. Patients receiving the transplant are at major risk for infection as they wait for their immune systems to regenerate: between 10 and 30% of patients die from the procedure. In addition, there are very few HIV resistant donors relative to the number of infected individuals. On average, 1 of every 1,000 Europeans carries 2 copies of the defective gene while the mutation (a 32 base pair deletion) is very rare in people of Asian and African descent.

The tidings are not all together grim, however. This case shows that HIV can be treated by inhibiting CCR5 expression. If a patient’s HSC could be removed, rehabilitated via gene therapy, and returned to the patient, future AIDS treatment might not require life-long drug courses or dangerous transplants.

Only recently has science began to unveil some of the mysteries of these behemoths. For decades it was believed that ancient DNA, proteins, and soft tissue could not be preserved over millions of years. Now, during the last 2 years, soft tissue was discovered deep inside the thigh bones of T-Rex.

There are times that inspiration for truth comes from science fiction, such as the best selling novel and blockbuster film, “Jurassic Park.” The film took some artistic liberty with their dinosaurian profiles. One of the most noticed was giving a carnivorous dinosaur known as Dilophosaurus a special skill – the ability to spit toxic venom.

According to their fossils, there was no evidence for venom production in this type of dinosaur. In fact to most paleontologists this idea was laughable. Today venomous dinosaurs might not be so funny.

A fossil of a small dinosaur called sinornithosaurus (a chicken-sized dinosaur) was discovered in China about 9 years ago. This species existed in the mid-Jurassic (about 124 million years ago). This find caused a sensation because it had clear evidence of feathering. In 2009 a research team studied the skull of this animal intensively and made an interesting discovery. They found mysterious air pockets located above many of the teeth. These “pockets” connected to grooves in the dinosaurs teeth that spanned from the base of the tooth to the tip. This would be the perfect mechanism for a venomous bite. Even though this new theory is controversial, it is a logical explanation.

If these little dinosaurs were poisonous, it may be impossible to tell anything about the venom itself. There would be no trace of it left after about 124 million years. The answer lies within their DNA. There is an unbearably slim chance of finding any soft tissue remaining in such a small fossil. This is always the problem for every paleontologist, we just have to take what we can get, and go as far as we can go – and hope for answers along the way.

For more information on this new discovery go to:  

http://www.sciencenews.org/view/generic/id/51402/title/Groovy_teeth_suggest_dinosaur_was_venomous

The amazing part of antibody production is the fact that the instructions on how to make so many of them are found in the DNA. DNA is divided up into segments, called genes, which have the instructions on how to make proteins.  If there are only about 23,000 genes in human DNA, how do our cells make so many different types of antibodies? The number of antibodies exceeds the coding capacity of DNA tremendously.   

This brings up a whole list of events that leads to antibiotic diversity, including the recombination of gene segments in the production of the protein. Multiple gene segments will recombine in the blood cells to form the heavy and light chain in the antibody. Just to give you an idea about how diverse they can be, the heavy chain itself has almost 11,000 different combinations that can result from the recombination of all of the gene segments. After a variety of antibodies are produced, random somatic mutations will occur which lead one specific antibody being able to bind to the antigen that is present.

To learn more about how cells read the instructions in DNA to make proteins, see http://www.dnai.org/a/index.html.

Cancer cells have mutations in their genes that render them unable to respond to signals that regulate cell division. These cells grow uncontrollably and can invade normal tissue in other locations of the body and cause disrupted functions of major organs. This is why cancer is so deadly.

A mutagen is a physical or chemical substance that can alter genetic material in cells. DNA can be damaged or changed (mutated). Cancer cells have changes in the genes themselves. These changes can include mutations , deletions of part or whole genes or even the addition of extra copies of genes.

There are many mutagens that can cause cancer in cells. These are called carcinogens. Two of the most common and most deadly cancers, lung and skin are caused by two well known carcinogens, cigarette smoke and sunlight. Some studies suggest when 15 cigarettes are smoked, an error in DNA occurs.

Now the UK’s Wellcome Trust Sanger Institute has cracked the code for the mutations within DNA that can cause tumors that lead to these two devastating types of cancers.

This new information can open the door to major advancements in treatment, medication and maybe even cures in the future of skin and lung cancers.