Example+of+synbio+research+project

Example 1
Research Project: Cyanobacterial Energy




 * Problem:** Fossil fuels have been the main source of energy around the world for decades. These fuels, such as oil and coal, pose several problems. They cause pollution which contributes to the greenhouse effect and thus global warming, and they are also non-renewable; we will soon run out of readily available fossil fuels. Alternative energy sources have been developed, such as solar, wind, hydropower, geothermal, nuclear, etc. Bioenergy, however, is the only type of energy that has been able to be used as fuel in current vehicles. Current biofuels are expensive and unable to compete with traditional fuels. Scientists have thus turned to synthetic biology to produce more cost-effective alternatives.


 * Solution:** Cyanobacteria are simple prokaryotes that produce a variety of chemicals that can be used as eco-friendly, sustainable fuel. While these are produced naturally, the efficiency of their production is inhibited by naturally limiting factors. Synthetic biology has allowed the modification of these organisms to maximize the production of these fuels.


 * Options:**
 * **Hydrogen:** Cyanobacteria may produce hydrogen through two different types of enzymes; hydrogenase or nitrogenase.
 * **Nitrogenase:** Heterocysts are bacteria that fix nitrogen. In their nitrogen-fixing processes, they use nitrogenase and produce H2 as a byproduct. This fixation occurs in an anaerobic environment, which synthetic biologists can produce by inhibiting PSII in these bacteria. The problem with this type of H2 production is that the H2 is quickly consumed by an uptake hydrogenase. Biologists are working on engineering a mutant which cannot recycle the hydrogen it produces. Another downfall of this method of production is that it uses a considerable amount of ATP. Hydrogenase presents another, more efficient method of production.
 * **Hydrogenase:** Bidirectional hydrogenases naturally found in many bacteria can either oxidize or produce H2. The problem with this enzyme is that it is intolerant to oxygen, and so oxygen must be constantly removed along with the H2. To combat this obstacle, certain attempts have been made to introduce enzymes which are less oxygen-sensitive to these bacteria. Another challenge of hydrogenase is its necessity for electron donors which cannot be met through natural metabolic processes of the cell. Synthetic biologists are working on directing electron flow away from other metabolic processes and towards H2 production


 * **Ethanol:** Ethanolcan be produced through fermentation. Previously, it has been harvested from crops. This is a controversial practice, as crops are food sources. Cyanobacteria are not food sources, and they ferment naturally when in the dark, unlike crops. Ethanol production occurs through a series of enzymes. The enzyme PDC converts pyruvates to acetaldehyde, which is in turn converted to ethanol by the enzyme ADH. This production is generally minimal, as it is limited to what the organism needs. Synthetic biology has allowed the engineering of strains that can produce greater amounts of ethanol through the overexpression of relevant enzymes. Ethanol is useful in powering cars; it can be mixed with diesel and used in diesel engines without their modification.




 * **Butanol:** Butanol has a higher concentration of energy than ethanol, closer to that of gasoline, and so may be seen as a more favorable alternative. Butanol can be produced through two distinct pathways. The synthetic 2-ketoacid pathway uses intermediates from amino acid production pathways. The intermediate, 2-ketovalerate, is decarboxylated and thus turned to 1-butanol. An alternative pathway, the coA-dependent pathway creates butyryl-CoA from acetyl-CoA and then reduces butyryl-CoA to 1-butanol. This pathway does occur in nature for the production of butanol, along with ethanol and acetone. Introduction of certain enzymes allowed synthetic biologists to concentrate this production, resulting in bacteria which create an average of 20 mL/day of butanol. Butanol is produced directly from CO2. Butanol can be used in petroleum engines, or mixed with diesel to be used in diesel engines.




 * **Photanol:** Photanal is the combination of chemiotrophic organisms and phototrophic organisms to create “photofermentative” metabolic pathways in the resulting microorganisms. Photanol may significantly increase the production of biofuels through the use of microorganisms e.g. cyanobacteria. The only products consumed in this system are H2O and CO2.
 * **Phototrophs:** Phototrophs are organisms which use energy from the sun’s light (photons) to power metabolic processes. One of these processes is the production of different types of C3 sugars during the Calvin Cycle of photosynthesis. These C3 sugars are used by these organisms in subsequent anabolic processes.
 * **Chemiotrophs:** Chemiotrophs are organisms which obtain energy through oxidation of organic and inorganic compounds in their environment. In chemiotrophs, the same C3 sugars produced by phototrophs play a role in catabolic processes. Chemiotrophs often break more complex sugars down into these C3 sugars, and then further degrade the latter into CO2 under aerobic conditions, and other products under anaerobic conditions.
 * **Combining the two:** synthetic biologists are working on engineering a combinations of phototrophs and chemiotrophs. An organism such as this one would, using phototrophic systems, be able to produce C3 sugars using only sunlight, water, and CO2, and subsequently use chemiotrophic systems to these sugars into products that can be used for as biofuels. The only byproduct of these processes would be O2.



//Sources:// [] [] [] [] [] [] [] [] [] [|http://webcache.googleusercontent.com/search?q=cache:twmdnxYzd48J:www.researchgate.net/publication/26251912_Alternative_routes_to_biofuels_light-driven_biofuel_formation_from_CO2_and_water_based_on_the_'photanol'_approach/file/32bfe50d065c844fd8.pdf+&cd=2&hl=en&ct=clnk&gl=us]

Example 2
=__ **Research: Artemisinin** __= There are an estimated 400 million reported cases of malaria, which result in around 1-3 million deaths. Malaria kills more than 2,000 people a day. Many of the victims were children in Africa, often under the age of five. This mosquito-borne infectious disease greatly affects the subtropical and tropical climates of the world, with the multitude of cases in sub-Saharan Africa and south Asia. The warm climate and humidity provide an excellent habitat for the mosquito larvae. Unfortunately, these areas are also the developing countries of the globe.
 * The Issue **
 * [[image:bli-biotech-research/Malaria Map.png align="left" caption="Malaria Map.png"]] ||
 * The area in red are Malaria Hotspots ||

** Miracle Plant ** The people in these regions are often hard pressed for adequate medical protection and they cannot afford the effective vaccines, and thus, many meet their ends. However, there is hope. There have been various treatments and vaccines, most notably quinine and chloroquine. Unfortunately, evolution kicked in. Various strains of mosquitos have developed resistance to the oft used antimalarial drugs. Enter to the global medical stage: artemisinin. In nature, artemisinin is found in the sweet wormwood plant, // Artemisia annua // (pictured below). The compound is then isolated and then manufactured as a drug. Recent studies have displayed that the antimalarial drug artemisinin has had a nearly 100% success rate in its patients. All point to artemisinin as the miracle drug of malaria. But just how does it fight the mosquito parasite? It goes into a telephone booth and changes- No. The process is quite simple. The drug basically releases oxygen based free radicals that target the mosquito parasite in the red blood cells. After the WHO (World Health Organization) declared artemisinin as the most effective weapon against malaria, ACTs (artemsinin-combination therapies) have become the standard treatment for the //P. falciparum// strain of the parasite. But there is a catch. A slight wrinkle in the silk. It has been mentioned earlier that artemsinin needs to be extracted from its natural source, the sweet wormwood. This means that the entire, global supply of the most effective drug against malaria is dependent on a crop that is temperamental, picky, and only able to grow in certain regions. Certain years may yield a plentiful harvest, and people are able to get their hands on treatment. But what about a decline? The prices would rise, and the people would have to suffer. The steady call for artemsinin for treatment has been pressurizing the delicate plant. The rapid increase of demand has left the supply exhausted. Herein lies the problem. We can no longer be reliant on a specific crop that produces that little amount of artemisinin. And it is here that we turn to the area of miracles: Synthetic Biology.
 * [[image:bli-biotech-research/Parasite In Red Blood Cell.gif caption="Parasite In Red Blood Cell.gif"]] ||
 * X-ray of the parasite in a red blood cell. It is very vulnerable at this stage. ||
 * Problems With Natural Synthesis **

The Institute at OneWorld Health and PATH’s Drug Development branch launched the program to synthesize a new source of artemsinin. The UC Berkeley team headed by Jay Keasling were also partnered with Amyris Inc and the pharmaceutical Sonafi. Extensive funding from the Bill & Melinda Gates Foundation were crucial to the research. These groups invested copious amounts of capital and effort into the ambitious project. Due to the relative new technologies of synthetic biology, there was not a great chance that the project would succeed as hoped. The doubts were replaced by relief soon after though. Jay Keasling and his team announced initial success in their endeavors in 2003. They figured that implanting genes into //E. coli// bacteria would enable them to produce a precursor to artemisinin, called amorphadiene, or artemisinic acid. These genes were obtained from three distinct organisms, among them yeast and the //Artemisia annua//. The team was able to make the //E. coli// bypass its natural metabolic pathway, in favor of the transplanted pathway. The product, the artemisinic acid, is then chemically transformed into artemisinin. The process can be seen below. The gray box represents the various metabolic pathways of the bacteria, eventually producing the artemisinic acid.
 * Here Come the Heroes **
 * [[image:bli-biotech-research/Jay Keasling.jpg caption="Jay Keasling.jpg"]] ||
 * Synthetic biologist Jay Keasling in the UC Berkeley labs ||
 * The Process **
 * [[image:bli-biotech-research/Artemisinin Map.gif caption="Artemisinin Map.gif"]] ||
 * A diagram of the general process, revolutionized by Jay Keasling and his team. ||

It is much cheaper, and far more efficient, to have the bacteria produce the precursor and turn the acid into artemisinin than it is to naturally extract the artemisinin from the plant. Thus, it is far more affordable for the impecunious families of the devastated victims. No longer is the global supply of artemisinin from the untrustworthy plants. Pharmaceutical company Sonafi has become the first producer of the semi-synthetic method of producing artemisinin. Furthermore, the process has been approved by the Pre-qualification of Medicines Programme (PQP), a subgroup of WHO. Sonafi plans to produce 35 tons of artemisinin this year alone, and roughly 55 tons this following year. This translates to an estimated figure between 80 and 150 ACT treatments. The company also announced that roughly one-third of the world's artemisinin would be synthetically produced this year. It was officially released April 11, 2013. Jay Keasling and his team at UC Berkeley subsequently launched Zagaya (“Spear”) to ensure that artemisinin is given at affordable costs to all people in the regions. Artemisinin is a part of the isoprenoid family. Isoprenoids are organic compounds composed of two or more hydrocarbons.
 * Success and Recent Advancements **
 * Ramifications **


 * [[image:bli-biotech-research/Artemisinin Formula.gif caption="Artemisinin Formula.gif"]] ||
 * The Artemisinin compound, a part of the isoprenoid family. ||

The other members of the family are used in combating other diseases, such as the anti cancer drug taxol. Such, the potential mass production of Artemisinin through the pathways of // E.coil // offer the same solution for these applications. The methods used by Keasling’s team should also apply to the other members of the isoprenoid family. One such example is the potential anti cancer drug, Eleutherobin, which is now found from a rare source. (in a rare form of marine coral). With the pathways used for the bacterial production of Artemisinin, the same can be used for that drug. Keasling has succeeded in opening the floodgates, by refining the techniques of synthetic biology and applying them to advocate for the amelioration of the world. After all, that is what science is for, is it not?

In his own words: Jay Keasling and his team talk about the project and what it means to help the world through science. [|Watch] If you can and are willing, please help Jay Keasling and his endeavors for a better future through the foundation Zagaya [|here]