Kira

Hey, I’m Kira. Here's my biography in the form of Q&A: I’m from a city called Grand Rapids, Michigan, about two hours from Detroit.
 * Where are you from? **

As a lover of science, I am passionate about all things biology. I am very interested in synthetic biology and the ethics behind it, as well as many forms of biotechnology and what researchers are doing to improve these fields. I am truly fascinated with genetics, DNA, heredity, insertion, mutation, embryology, and so many other areas of biology.
 * Why are you here at the Biology Leadership Institute? **

My interest in science and biology began when I was very young. The basis of life as we know it has always fascinated me. When I found that I could actually found out where life came from, why we are here, and all of the other prodding questions in all of our more nerdy brains, I was enthralled. This opened up an entirely new focus on the pathway my life would follow, and I knew that my creativity and desire to learn would make for a whimsical journey towards the many fields of biology.
 * How did your interest in science/genetics/biology start? **

In the future, I would love to be a doctor. I am really interested in the medical field, including embryology, anesthesiology, etc. I also love genetics, but honestly, I’m not sure how I feel about research.
 * What do you want to do in the future? **

As far as some general school experiences, I was elected as President of my 11th grade economics class, in which we ran our own business selling a product. I have participated in choir for many years, and, after a vigorous audition, I was selected to become a part of my school's Chamber/Jazz Choir. PALS, or Peer Assisted Learning, has also been a big part of my life. It is a program for students of all ages who need to be helped and listened to by students like myself. Being nominated to guide younger students towards a healthy lifestyle/mindset, provide tutoring if needed, and help them come to a conclusion about real-life issues on their own has been extremely fulfilling. Another school experience includes last year (2013), when I had the honor of performing as the lead in my school's spring musical, Brigadoon.
 * What school experiences have you had (in school or otherwise)? **

I have also had many biological experiences in school; I have taken various helpful courses such as Biology, AP Biology, Chemistry, Forensic Science, and whatever else I can’t think of at the moment. Furthermore, I have performed labs involving Gel Electrophoresis, PCR Amplification, etc., classified organisms, and various other tasks that will be very beneficial in this program.

I love music, art, and science. I have performed in musicals, I sing, I write music, I play a little bit of piano, and ultimately, I love to create.
 * Any hobbies, sports, or special/unique interests? **

You may be surprised by the fact that despite being in a grudgingly average public high school, I have been able to achieve a top-ten standing. I strive to be good. I make mistakes, I am human, but I love knowing that no matter what, I can do it.
 * <span style="font-family: Georgia,serif;">What have you done that might surprise us? **

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif; font-size: 200%;">Synthetic Biology: Artemisinin <span style="font-family: 'Times New Roman',Times,serif; font-size: 120%;">By, Kira Hooker

<span style="font-family: Georgia,serif;">On April 11, 2013, a revolutionary, partially synthetic, anti-malarial drug called Artemisinin will finally begin large-scale production. Jay Keasling, a professor of chemical engineering, has been working on the synthesis of semi-synthetic Artemisinin for about twelve years; only now is the breakthrough drug being released. A plant called Artemisia annua, the sweet wormword plant, produces artemisinin, a chemical with the extremely potent ability to treat malaria.



<span style="font-family: Georgia,serif;">The extracted artemisinin is then turned into a drug called artesunate and then mixed in with another antimalarial drug. This process is known as ACT (artemisinin-based combination therapy) and has been recommended for use to treat Malaria. Instability reigns however, as ACT manufacturers struggle. The supply for the plant-derived chemical has declined as the global demand rose dramatically since the World Health Organization recognized ACTs as the best way to treat the disease. Shortages and high prices have consequently followed, and the therapeutics of malaria has fallen. As an affordable source of artemisinin is needed, Keasling and his researchers began their exploration in the possibility that Artemisinin could be synthetically produced.



<span style="font-family: Georgia,serif;">This is a monumental discovery in the field of synthetic biology, as malaria affects millions of people all around the world. It all begins with Plasmodium, a parasitic protist, which infects a certain type of mosquito that feeds on human blood. When the parasite coming from the mosquito is introduced into the circulatory system, the Plasmodium travels to and multiplies in the liver.



<span style="font-family: Georgia,serif;">Common symptoms of the disease include fever, headache, chills, and vomiting, setting in about 10-15 days after the bite from the mosquito. If the malaria is not treated properly, it can cause improper blood distribution throughout the body, preventing the adequate supply of blood to many vital organs. This may progress to coma or even death.



<span style="font-family: Georgia,serif;">This disease is widespread more among the tropical and subtropical regions, including but not limited to sub-Saharan Africa, Southern Asia, and America. Every year, approximately 500 million people around these areas become infected with Malaria. Of these, about three million – mostly children – die from the merciless disease. This is largely due to the fact that, as mentioned above, the victims’ symptoms were not properly treated or not treated at all, perhaps because of the high-cost-only anti-malarial drugs that lead many to poverty – and if they cannot afford it – death.



<span style="font-family: Georgia,serif;">Strains of Saccharomyces cerevisiae, otherwise known as baker’s yeast, can be developed to yield artemisinic acid, a predecessor of artemisinin. A biosynthetic pathway has finally been developed in order to produce artemisinin through the use of biologically generated artemisinic acid. The actual metabolic pathway involves combining 10 genes from three difference organisms, bacteria, yeast, and plants. These genes are united into one bacterial chassis, or the “frame” for the internal workings of a specific biochemical function. The genes produce enzymes; acetyl coenzyme A is then turned into artemisinic acid. The resulting product can be purified and transformed into Artemisinin inexpensively. This technique avoids the use of pricey photochemical equipment and biosynthetically produces safe Artemisinin to be used for the major malaria crisis that has taken over many regions that fall under the broad band around the equator.



<span style="font-family: Georgia,serif;">Studies have shown that artemisinin exhibited a near 100-percent success rate when treating any known malarial strain. The parasite causing malaria is destroyed by artemisinin by releasing many oxygen-based free radicals. These attack the parasites residing in the red blood cells. “The artemisinin produced by this semi-synthetic process will substitute directly for the artemisinin from the plant, so there will be no difference in the final ACT product,” Keasling explains. Only the price will be affected, and the efficiency in which the product will be produced. One cannot even begin to explain the immeasurable benefits that will come of Keasling and his team’s findings. This is just one more step towards creating a safer, healthier world, where malaria will no longer be a life or death issue. Synthetic biologists are saving the world, discovery to discovery, one breakthrough at a time.



<span style="font-family: Georgia,serif;">Thank you so much for your time and interest in this subject! The world thanks you, too. :)

<span style="font-family: Georgia,serif;">Other Sources to check out:

http://www.youtube.com/watch?v=dHGApEGcbQ8#action=share

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif; font-size: 200%;">The Design: "BaPteria" <span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif; font-size: 110%;">Created By Kira Hooker

Scientists have been measuring the effects of smoking for many, many years. We know that long-time exposure to cigarette smoke means carcinogens perilously accumulating in the lungs. Exposure to certain carcinogens, such as benzo[a]pyrene, may lead to damage in the reproductive system, gastrointestinal irritation, skin irritation, and cancer. Benzo[a]pyrene is classified as a PAH compound, otherwise known as a polycyclic aromatic hydrocarbon. Many PAHs have been found to be carcinogenic, mutagenic, and teratogenic. Benzo[a]pyrene is listed as one of these pollutants, yet people continue to inhale these substances, damaging their bodies and giving themselves voluntary cancer.
 * Purpose **

This is an obvious problem that needs solving. Researchers around the world have tried to cure the epidemic of cancer that seems to continue spreading past the knowledge of our finest minds.



If there was a way to slow or even stop these devastating consequences, the effects of cigarette smoke in the lungs may dwindle. This would be a monumental discovery: curing of one of the many sources of cancer. A carcinogen is defined as any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. Cancer by carcinogens may be due to damage to the genome or disruption of cellular metabolic processes. Usually, if the DNA is severely damaged by carcinogens or otherwise, apoptosis (programmed cell death) will take place. If the cell death pathway is damaged, however, the cell will further mutate and become a cancer cell. Benzo[a]pyrene is one of the most prominent carcinogens in cigarette smoke. When the body attempts to metabolize benzo[//a//]pyrene, the resulting compound, diol epoxide, reacts and binds to our DNA, resulting in mutations and eventually cancer. A study conducted in 1996 provided evidence that linked components of tobacco smoke (which includes cigarette smoke) to lung cancer. Benzo[a]pyrene (or BaP) was proven to cause genetic damage in lung cells, which was identical to the damage in the DNA of malignant lung tumors. The purpose of my bacterial design is to eliminate the cancer-causing benzo[a]pyrene carcinogen within the lungs. Using bacteria with the ability to survive within the body’s upper respiratory tract, certain genes from one bacterial cell that code for the metabolism of BaP, which cannot necessarily survive in the lungs, will be inserted into the genetic sequence of another bacterial cell that can. These genes will code for taking the BaP carcinogen and adding enzymes until CO2 is ultimately produced. The remaining CO2 product will then be exhaled.

As far as scientists are concerned, little information is currently known about the levels or repair of the damaging of DNA by carcinogens. These limitations are mainly due to sensitivity in humans; the only data we have so far comes from adult occupational exposure studies or animal experiments. The only known ways to prevent the harmful outcome of carcinogens on the lungs include the body’s natural attempt to metabolize benzo[a]pyrene. Though this is often even more destructive, it is the only way we know to react to this foreign substance that invades the lungs and overtakes the system slowly, silently killing us. As there are no other competing technologies to address this hazy crisis, the likelihood of scientists solving the said issue of carcinogens is slim to none.
 * Competing Technologies **

For my design, called “BaPteria,” a // Haemophilus influenzae // bacterial cell would be used to conduct the metabolizing of carcinogens in the lungs. It has a niche specificity to live in the upper respiratory tract. As of now, scientists have found many strains of this specific bacterium to be opportunistic pathogens; the bacteria will survive in their host without causing any sort of disease until some other factor (i.e. reduced immune function, viral infection, etc.) create an opportunity to infect the cells. In 1995, //H. influenzae// became the first free-living organism to have its entire genome sequenced. This can only lead to more discoveries pertaining to the bacteria – researchers may eventually have the ability to alter the bacteria in such a way that would create a non-pathogenic strain that could be released into the lungs. This can be left as a “black box” of sorts in my design.
 * The Design **

To further this design, I intend to use two specific genes from bacteria called //Mycobacterium vanbaalenii,// a non-pathogenic, risk group 1 bacteria. This is the first known microorganism to have the ability to degrade/metabolize polycyclic aromatic hydrocarbons (such as benzo[a]pyrene). Using a pathway called the PYR-1 pathway, //M. vanbaalenii// has been shown to be able to take BaP and metabolize it with the help of many different enzymes, eventually leading to the product of CO2. This is what I propose to be exhaled after the various processes of the PYR-1 pathway.



This PAH degradation pathway, as mentioned, begins with a benzo[a]pyrene molecule. Using an enzyme called benzo[a]pyrene cis-4, 5-dioxygenase, benzo[a]pyrene-cis-4, 5-dihydrodiol is created. From there, benzo[a]pyrene-cis-4, 5-dihydrodiol dehydrogenase is used in producing 4, 5-Dihydroxy-benzo[a]pyrene. With the help of 4, 5-dihydroxy-benzo[a]pyrene dioxygenase, 4,5-Chrysene-dicarboxylate is constructed; 4,5-chrysene-dicarboxylate decarboxylase is then used to get Chrysene-5-carboxylate, a final factor in the production of CO2.

There are two genes that code for both the small and large subunits of a PAH dioxygenase, an enzyme that is responsible for catalyzing the oxygen atoms in O2 into one substrate, //nidA// and //nidB//. Both have been shown to be involved in the //M. vanbaalenii// bacterial PAH degradation pathway. It can be concluded that these genes can be taken and objectively inserted into a //H. influenzae// bacterial cell. This may lead to aerobic, synthesized bacteria that could potentially degrade the carcinogens straight from the lungs.



The cell would respond to the stimulus of benzo[a]pyrene, though it is undetermined how the cell would detect the compound. Presumably, the genes //nidA// and //nidB//, inserted from an //M. vanbaalenii// bacterium into the //H. influenzae// bacterial cell would cause the PYR-1 pathway to continue and the synthesized cell would be able to identify the BaP on its own. The new genes expressed would be responsible for metabolizing carcinogens, and the bacteria would be able to survive in the lungs because of the aerobic host cell (//H. influenzae)//.

While inventing the bacterial design, some of the genetic devices would have to include the ability to sense benzo[a]pyrene in the lungs, survive in the lungs (be aerobic and stable in the upper respiratory system), be non-toxic and non-carcinogenic; the bacteria must be able to degrade or consume polycyclic aromatic hydrocarbons (PAHs). There would have to be a device to terminate the reproduction of the bacteria. If this could not be done, then the non-pathogenic strain of bacteria would have to be able to trigger the immune system in such a way that it would automatically be flushed out. It would have to outcompete other bacteria in the lungs. Another example of criteria, yet not specifically a genetic device, would involve a concentrated dose of the bacteria to be administered through a metered-dose inhaler (MDI) in aerosol form.



Fortunately, genes //nidA// and //nidB// that come from the //M. vanbaalenii// already code for the degradation of benzo[a]pyrene as mentioned above. This strain of bacteria is non-toxic, non-pathogenic, has regioselectivity in degrading compounds and forming others, and already has developed a technique for metabolizing BaP, hence “BaPteria.”

When the design system is working perfectly, I would expect the cell to degrade the BaP compound and form CO2. If benzo[a]pyrene (inducer) is present, then the repressor will bind and will not be able to bind to the operator. The RNA polymerase will have the ability to continue transcribing the DNA onto the mRNA, which will synthesize a PYR-1 protein. This protein begins the metabolism of BaP into CO2.
 * Expected Results **

These results would bring about a successful solution to the problem because as said, exposure benzo[a]pyrene is exposure to polycyclic aromatic hydrocarbons, which have been shown to be highly carcinogenic. These bacteria could be the key to eliminating lung cancer due to the benzo[a]pyrene hydrocarbon by breaking it down into a substance that can simply be exhaled.

Advantages My biological design is an advantage over the existing technologies because there are little ways to eliminate carcinogenic activity without actually quitting smoking or becoming exposed to these carcinogens, some of which simply cannot be avoided. With a regular dose from this “BaPteria” Inhaler, the carcinogen would be eliminated in a safe, close-to-natural way – health by bacteria.

This design is worth funding because it will be the safest and most effective way to rid the body of benzo[a]pyrene, a leading carcinogen that absolutely will cause lung cancer over long periods of exposure. Smoking has always been a horrible addiction. Now that scientists have found the consequences of the action as well as the causes, we have finally found the solution. Funding this project would save millions of lives around the world – we would be just another step towards fulfilling the health needs of the global population and eliminating one major source of cancer in the process.

Potential Problems Some potential problems include the inability for the plasmids from one bacteria to function within the plasmid DNA of the other bacteria. There may not be a way to synthesize the // H. influenzae // in such a way as to give it the same qualities as the non-pathogenic, Risk Group 1 //M. vanbaalenii// bacteria. These different species of bacteria may not work with each other, in that the final product may not have the ability to survive in the human body’s respiratory system, etc. “BaPteria” may not succumb to the body’s immune response, and could cause an epidemic within the lungs, though this is highly unlikely if the bacteria is non-pathogenic and non-toxic as planned. For the safety of the employees, there would have to be many precautions, probably including Biosafety Level 4. The potential rewards of this design go above and beyond, completely prevailing over the risks. If the project does not turn out as planned initially, scientists could be working on it for years to come, eventually finding ways to improve the proficiency of the bacteria and its unimaginable advantages.

Testing Various testing experiments have already been conducted regarding the PR-1 degradation pathway of benzo[a]pyrene, so scientists already know that the metabolism will operate properly. The few things that researchers would have to investigate include whether the genes could be properly expressed from the characteristics desired from each bacteria.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif; font-size: 200%;">The Prezi: http://prezi.com/g9gokrztgxhs/present/?auth_key=4zhh17a&follow=imv-ymbgvwvu

<span style="font-family: Impact,Charcoal,sans-serif; font-size: 200%;">Citations: **<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif; font-size: 180%;">Research Sources ** <span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"Expanding Nature’s Toolkit: How Synthetic Biology Is Changing the Face of Medicine." Sciencebuz. Sciencebuz, n.d. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Yarris, Lynn. "Synthetic Biology Offers New Hope For Malaria Victims." Science Beat. Berkeley Lab, 24 Mar. 2004. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Paddon, CJ, PJ Westfall, and DJ Pitera. "High-level Semi-synthetic Production of the Potent Antimalarial Artemisinin." National Center for Biotechnology Information. U.S. National Library of Medicine, 10 Apr. 2013. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"High-level Semi-synthetic Production of the Potent Antimalarial Artemisinin." Nature.com. Nature Publishing Group, 10 Apr. 2013. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Sanders, Robert. "Launch of Antimalarial Drug a Triumph for UC Berkeley, Synthetic Biology." UC Berkeley NewsCenter. UC Berkeley, 11 Apr. 2013. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Sawyer, Eric. "Artemisinin: A Synthetic Biology Success Story." Nature.com. Nature Publishing Group, 23 June 2011. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"About Malaria." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 09 Nov. 2012. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"Malaria." WHO. World Health Organization, 2013. Web. 12 July 2013.

**<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif; font-size: 180%;">Design Sources ** <span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Zhang, Edward. "Benzo(a)pyrene Pathway Map." Benzo(a)pyrene Degradation Pathway. University of Minnesota, 10 Nov. 2011. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"Mycobacterium Vanbaalenii." Mycobacterium Vanbaalenii. MicrobeWiki, 19 Aug. 2010. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"Mycobacterium Vanbaalenii." Wikipedia. Wikimedia Foundation, 22 May 2013. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Moody, Joanna D., James P. Freeman, Peter P. Fu, and Carl E. Cerniglia. "American Society for MicrobiologyApplied and Environmental Microbiology." Degradation of Benzo[a]pyrene by Mycobacterium Vanbaalenii PYR-1. American Society for Microbiology, Jan. 2004. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Kim, Seong-Jae. "American Society for MicrobiologyJournal of Bacteriology." Complete and Integrated Pyrene Degradation Pathway in Mycobacterium Vanbaalenii PYR-1 Based on Systems Biology. American Society for Microbiology, Jan. 2007. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"Benzo(a) Pyrene." Pollutant Fact Sheet. Scottish Environment Protection Agency, n.d. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">"Benzo(a)pyrene." Wikipedia. Wikimedia Foundation, 07 Nov. 2013. Web. 12 July 2013.

<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Tobacco Smoke Carcinogens and Lung Cancer. JNCI J National Cancer Institute, 1999. Web. 12 July 2013. <http://jnci.oxfordjournals.org/content/91/14/1194.full.pdf+html>.