Kevin+Wu

Week 3: Gene editing through TALENs

This week in class we debated whether we would utilize gene editing in order to cure genetic diseases (or for cosmetic reasons). The question that repeatedly arose was "Assuming it is possible, would it be safe?" In order to answer this question, I researched one method of gene editing, Transcription Activator-Like Effector Nucleases

Gene editing: Plausible?

First of all, lets learn how genomic editing works. "Genomic editing is a type of genetic engineering in which DNA is inserted, replaced, or removed from a genome using artificially engineered nucleases, or "molecular scissors."' Although, this may seem simple enough, scientists predict that it will be decades before this technology can be used by humans. Transcription Activator-Like Effector Nucleases (abbreviated to TALENs), works in a similar way, although many complications prevents the. safe use of this technique in humans.



Often times, the cause of diseases such as cystic fibrosis, stem from broken genes. One of the greatest difficulties with finding and fixing these broken genes is finding them. This is where the TALEN comes into play. The TALEN is a combination of the TAL plant bacterial gene, and an endocuclease, which will allow the TALEN to cut the broken gene. The TAL is an interesting gene that can recognize unique DNA sequences for genes that can allow the bacteria to enter the cell (normally harmful to plants, but useful to scientists in this case!), it also is able to locate the broken genes that need cutting.

Once the broken gene is found, the next step is to repair it! Once the endonuclease cuts out the "broken" segment, the correct segment must replace it. Because cells do not "know" the correct gene configuration, scientists must step in and add the missing DNA sequence. From there, the cell takes over and fixes the mistake in the DNA. This is done through a process called homologous recombination, where nucleotide sequences are exchanged between two identical strands of DNA.



One of the biggest reasons this new tool cannot be used to cure more complicated diseases like cancer where lot of genes are effected is because it would require scientists to make a different pair of scissors for each broken gene, and as the the number of "scissors" floating around in our cells increases, so does the rate of error.

While the technology works, like the cures being researched at Janssen, this process must be thoroughly tested before it can be applied to humans. Scientists predict we are at least 5-10 years away from seeing this technology being used in patients. It must first be tested on a small number of patients, and if all goes well, this technology may be used in hospitals around to world to cure genetic diseases.



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Week 2: Hydraulic Fracturing: Whats the Big Frackin' deal?!

What is "Fracking"?
Hydraulic Fracturing, or "Fracking," is a new technique that allows for economical extraction of natural gasses that were once unreachable, with just water. Although it may seem like a great concept, it has spurred a great amount of controversy. So what's the big Frackin' deal?

Well in order to understand what Fracking is and just how much it can impact the environment, you have to understand how it works. First, Trucks must bring water and supplies to and from the Fracking site. On average, each gas well requires around 400 tanker trucks in order to transport all of the supplies. At the Fracking site, the water must first be treated with sand and chemicals to help it fracture shale with efficiency. Some of the chemicals added to the water include Lead, Mercury, Uranium, Ethylene Glycol, Radium, Methanol, Hydrochloric Acid, and Formaldehyde (Keep in mind that most of this treated water ends up in the ground, bodies of water, and the air.) The water is then injected 10,000 feet into the ground, where the high pressure causes nearby shale rocks to fracture and release natural gas into the wells for collection. At these depths, toxic chemicals from the Fracking solution often leaks out into nearby bodies of water. Finally, around 40% of the Fracking water is recollected and is left in air pits to evaporate into the air. **The rest of it is left in the ground, and is not biodegradable**

**Somewhat** unbiased video that explains the process of Fracking and its effects. media type="custom" key="26110230"



Some interesting statistics
Fracking can produce 300,000 barrels of natural gas per day.

There are an estimated 35,000 fracking wells currently in the US.

Toxic wastewater produced in 2012 - 2 billion gallons.

Air pollution in one year (tons) - 450,000.

Water used since 2005 - 250 billion gallons

Chemicals used since 2005 - 2 billion gallons

**Why does this matter to me?**
In addition to harming the environment, Fracking can have harmful effects on local communities as well. Fracking will often lower the property values of nearby areas. Also, If the natural gas wells are not completely secure, gas can get out of the well and into the water supply (and the water you drink), which can lead to this:

Fracking also requires the clearing of land to build new access roads and well sites.

This is especially relevant to those in Pennsylvania (That's us!) because of the Marcellus Shale, a sedimentary rock buried thousands of feet beneath the earth's surface

Drilling wells in PA.

**Is it worth it?**
The reason why we go to such great lengths for Fracking is because it allows us to collect previously unattainable sources of natural, essentially unlocking massive new supplies of clean energy (natural gas burns far cleaner than other fuel sources). The lengthy complex process also helps create many jobs. Engineering and surveying, construction, hospitality, equipment manufacturing and environmental permitting are just some of the professions required for Fracking. By 2012, more than 30,000 have been employed by the oil and gas industry **in Pennsylvania alone**. Fracking can also boost local economies by generating royalty payments to property owners and providing tax revenues to the government. Fracking supporters also claim that precautions are being taken to lessen the environmental impact.



Environmental Precautions :
Cementing of pipes ensures integrity and prevents leaks.

The EPA have confirmed effectiveness of groundwater protection methods.

Water for Fracking is taken from multiple different sources based on availability in order to lessen impact on local water supply.

Sources of air emissions as a result of Fracking are only temporary.

Routes to wells are selected to maximize efficient driving and public safety (avoidance of peak traffic hours, school bus hours, community events, and overnight quiet periods).

[|Ted talk supporting natural gas and Fracking]media type="custom" key="26110188"

Still interested? Check out these other sites!

http://www.energyfromshale.org/hydraulic-fracturing (Supports) http://www.what-is-fracking.com/ (Supports) http://www.dangersoffracking.com/ (Opposes) http://en.wikipedia.org/wiki/Hydraulic_fracturing (Unbiased)

= = = = = = = = = = = Week 1: Separation of Germ Cells and Somatic Cells =

A recent study at the University of Michigan has proposed the hypothesis that Mutagenic consequences associated with performing metabolic work has led to the separation of germ cells (a cell that gives rise to gametes), and somatic cells (any cell that is not a germ cell, gamete, gametocyte, or undifferentiated stem cell) in order to protect genetic material. This protection of the genetic material greatly reduces the amount of harmful mutations that can be passed down to offspring. This is important to organisms such as our plants, in order to create healthy offspring free of multiple harmful mutations.



You can also think of it as a colony of bees working together in a hive. The worker bees subject themselves to danger by protecting the hive from intruders and pollinating flowers, while the Queen Bee (the germ cell in this example), remains isolated in the hive, maintaining the hive's population. This can also apply to many other species, such as ants.

This hypothesis, dubbed "The Dirty Work Hypothesis," was tested using a digital simulation, called Avida, which I thought was very interesting. In the simulation, a group of multicellular organisms with undifferentiated cells were created. A group of these organisms began diverting most of the metabolic work towards a subset of germ cells. Those organisms later removed the reproducing capabilities of those cells, creating somatic cells and germ cells. You can see in the picture below how metabolic activity (and therefore mutational load) was first concentrated into certain germ cells, which after losing reproductive capabilities, became somatic cells.



Another thing I found interesting was that in early stages of the experiment, the organisms without separation of germ and somatic cells reproduced just as well, however once competition between organisms was introduced into the simulation, metabolic activity increased, and along with it, the rate of mutation.



ALSO, because somatic cells are free from reproductive burdens, they can complete more complex tasks, benefiting the organism. However, as these cells take on most of the metabolic activity, they also take on the most mutation. This bombardment of mutations can cause aging in the cells, as well as the organism.

If you'd like to find out more about this fascinating study, check out these links!

http://www.sciencedaily.com/releases/2014/05/140522141453.htm http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001859 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001858 http://www.nature.com/scitable/blog/accumulating-glitches/evolving_separate_tasks_8212_how