Brian

 Hello my name is Brian. Well actually it used to be Bhrian. I'm pretty sure it was Brian first though. I'm going to be a rising junior at Roy C. Ketcham Sr. High and I live in the "Vassar Bubble" of Poughkeepsie. The town of Poughkeepsie is so well known that the wiki tries to tell me that I must be spelling it incorrectly. Unlike New York City, the town of Poughkeepsie is quiet, serene, and most of the time downright boring. The summers are hot, the winters are filled with snow, but one thing remains the same, the fact that there is nothing to do. That is, unless you go out and look for things to do. Something such as BLI...



 My sophomore year was filled with chemistry and AP World. On the side, I was busy playing piano for our school pit orchestra or training for tennis. With all my friends in the grades above me stressed about colleges and majors, I was also pulled into thinking about what I wanted to study in college. I was (and still am) stuck between Engineering, Biology, and Business. I became especially interested in Biotechnology in my freshman year, when I was taking both Honors Bio and Business Law. One of the end of the year projects I did was exploring the role of business in the medical field. Not only is Biotechnology or Synthetic Biology a growing field, it is also providing new opportunities for business. Synthetic Biology also helps to combine the fields of Biology and Engineering, which is not something I thought could have been possible. My goal for this camp is to explore the my interests and find out if biology is truly the way to go for me. I would also love to explore the business opportunities in this field.

 In my school, besides being involved in the yearly Masque and Mime spring production, I'm also part of our school's Science Olympiad, and Math team. (shush) Although our school failed to make States this year (lesgo RCK Indians!), I truly learned a lot learned a lot and had a lot of fun working with my friends on projects. Science Olympiad helped me explore many different fields of science. I helped build a Boomilever out of balsa wood, studied epidemiology, played with Legos, and even filled in for a Physics event when one of our team members was missing. After getting a feel for many different areas, I realized that sometimes you really need to explore for yourself to see what interests you. Sometimes, it isn't what you would expect. I enjoyed Disease Detectives immensely, but on the other hand, I came to the conclusion that physics probably wasn't the thing for me. I had a similar experience with Math Team. Although I am good at math (2+2=.......4?), after being on the team and training that brain, I knew that advanced math wasn't my calling. It was fun to do in school, but I knew I would hate having a job that involved doing calculus every day. I believe that being involved in "da pit" and being on the Varsity tennis team not only helped me realize the importance of hard work, but also the importance of the little details. The pit, although not usually recognized by most of the audience (-___-), is a key part of any successful production. A lot of people in the audience don't realize that the pit spends just as much time rehearsing as the cast. Somewhat ironically, when the pit sounds good, no one notices. However, when the pit sounds bad... the musicians are suddenly put in the spotlight! Production week (aka he!! week) is comprised of sleepless nights practicing and practicing and practicing. That one melody that you can't seem to get down could make the difference between a smooth performance and an utter train wreck. Playing tennis and losing has helped me realize that people fail. Small mistakes can make a difference. That one overhead that you missed in the last game. That one backhand that you shanked on match point. People (epic) fail all the time, but its is important to keep trying until you succeed :D

(^^^^^^^^.^^^^^^^) //(2nd on the left *cough cough*)//  I feel that all my experiences have really driven my interest in science. Science now is headed towards bigger things through smaller mediums. In science, details are absolutely crucial. In science, people fail all the time, but these failures can lead to even greater successes. I hope this program can help me explore the field of Synthetic Biology and Biotechnology and steer me in the right direction for the future.

=**Research Project: Biosensors** =

 Biosensors. What are they? Basically, a biosensor is a device that utilizes biological components to indicate the amount of a biomaterial.



 Biosensors have three components, the sensitive bioreceptor, the transducer, and the reader device. The bioreceptor is anything that can interact with the analyte (substance or chemical of interest). Examples of bioreceptors include microorganisms, tissues, organelles, antibodies, enzymes, and nucleic acids. This is where the advancements in synthetic biology have come into the field of biosensors. Either through modifying existing genes or creating new ones, biologists have helped to make bioreceptors that are sensitive to a multitude of things such as dangerous chemicals, heavy metals, or pathogens. Cells are most commonly used because of their sensitivity to the environment and ability to respond to all kinds of stimulus. The ability for a cell to reproduce is also crucial in its role in detecting stress levels/toxicity in the environment. Bioreceptors often have to be attached to the surface of the sensor. In the case of cells, the surface of the sensors contain polylysine, epoxylysine, or aminosilane to immobilize the cells and then layer by layer deposition of alternately charged coats of polymers bind the cells in place.



 After the analyte is detected by the bioreceptors, the tranducers help to convert the signals resulting from the interaction between the analyte and the receptor into a signal that can be more easily measured. There are six different types of transducer.

 The signal emitted by the transducers can then be converted into electrical signals and eventually be easily displayed on a reader device such as a computer. The signals can also be converted to into a form that can be seen easily by the human eye, such a change in color.





 Biosensors have come a long way from the times of Professor Leland C. Clark Jr. (1956), the father of the biosensor. The uses of biosensors in the modern world focus on the areas of Industry/Agriculture, Medicine, and Military. The military is increasingly becoming involved in the development of biosensors. Recently, there has been a lot of research done on landmine detecting bacteria. The military is also focused on using biosensors to monitor battlefields for chemical weapons such as nerve gas and detecting airborne bacteria in counter-terrorism activities. In Medicine, biosensors have already been making an impact, from glucose monitoring to pregnancy test strips. New biosensors that are currently in testing include sensors that can detect bladder cancer and lyme disease. Recently, a team of scientists have been able to make a "artificial skin" using flexible sensors. This revolutionary biosensor can detect temperature, humidity, and touch and help advance prosthetic technology immensely. In Agriculture, with the heavy metal or chemical contamination occurring all over the world, people are continuously searching for new ways to detect the presence of harmful substances in the environment. Bacteria have already been created that can detect heavy metal ions, ammonia, arsenic, and most recently, Brazilian researchers have been working on a biosensor that can detect the amount of pesticides in produce, water, and soil. Using enzyme inhibitors, nanoparticles, and an ultrathin film, they have been able to make the sensor the size of a thumb. This new biosensor will help farmers especially in testing their fields and getting immediate results, as opposed to conventional testing methods which involve chromatography or spectrometry and are often very expensive.



Although scientists are making huge progress in, there remain several barriers to overcome. The biggest goal for biosensors is to make them small, portable, and easy to use. The most successful biosensors (the glucose monitoring system and home pregnancy test) were cost effective, provided a necessary service, provided almost immediate results, and were portable/easy to use. On the other hand, a cholesterol monitoring system was largely a failure because the cost was high and it did not provide any immediate benefits. (What are you going to do with your cholesterol score? Cholesterol effects are long term!) Manufacturers are continuously looking for new ways to mass-produce biosensors in an effort to lower costs. Cost is a crucial factor, especially for sensors that are meant for "home" use. One of the main problems that the Brazilian Pesticide Sensor is that although it is extremely portable and convenient, it still comes with a price tag of almost $100 per sensor.

The area of biosensors is growing quickly because of its economic value and demand from all over the world. As technology continues to improve and biologists discover more ways to detect different analytes, the effectiveness and efficacy of biosensors will continue to advance. Without a doubt, biosensors will make the world easier and safer to live in.

=Design Project: Synthesis of Factor VIII Through Bacteria=

<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">Hemophilia is a genetic disorder that affects the ability of the body to control blood clotting or coagulation. Hemophilia is a rare, but definitely not uncommon disease. Currently, about 17,000 people in the U.S. have either Hemophilia A or Hemophilia B. People with hemophilia have to be careful not to injure themselves because even small external cuts or internal bruising could all result in severe bleeding.

<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">

<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">Normally, when a person gets gets a cut and a blood vessel is broken, collagen, von Willebrand factor (vWF), and tissue factor is released. When the platelets in the blood react with the factors, they clump together and start to "activate" by changing into a stellate shape and releasing vWF, growth factor, fibronectin, B-thrombogobulin, fibrinogen, and clotting factors V and VIII. As thrombin begins to react with the fibrinogen, a fibrin "net" is formed that works with the buildup of platelets to effectively "clot blood". However, without the coagulation factors (notably factor VIII and IX), the fibrin cannot form and therefore although a temporary scab will be created, the wound will continue to bleed. Hemophilia A is when the body either does not produce enough factor VIII or produces "defective" factor. (Hemophilia B is more rare, body has a factor IV deficiency) This means that hemophiliac will bleed for a much longer time than the average person. Some common misconceptions about hemophiliacs are that they bleed "harder", or that they don't have enough platelets. In actuality, people with hemophilia bleed at the same rate as "normal people" and have the same platelet count. The only difference is the lack of Factor VIII. If Factor VIII is put into the body, hemophilia is not a problem anymore! Sounds simple, right? Not really.

<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">**Proposal**: Using //E. coli,// create a topical creme containing bacteria engineered to produce clotting factor VIII in order to help close external wounds for people with Hemophilia A. This is extremely important due to the fact that even small cuts can be harmful to a hemophiliac, as clots are unable to form and bleeding continues. Thousands of people all over the U.S. are affected by Hemophilia A and have to live careful lifestyles due to the dangers of common cuts. This design will help to aid blood clotting on external wounds and therefore prevent complications from blood loss.

<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">**Competing technologies:** Currently although there are a multitude of treatment options that can help hemophiliacs live normal lives, not all of them are efficient, safe, or cost-effective. There is currently no cure for hemophilia, although gene therapy is a promising solution, it has not proven to be successful at this point. Replacement therapy, one of the most common methods, involves using human blood to make concentrates of Factor VIII. Although modern screening techniques have greatly reduced the risks of acquiring a blood-borne disease such as hepatitis, there remains a constant risk. "Lab-made" factor concentrates are very expensive but can guarantee that no diseases will be passed through the replacement therapy. Another problem with replacement therapy is that the factor must be injected into the vein. Similar to red blood cells, Factor is constantly being broken down and replaced, however, in the case of hemophiliacs, that means that a person must inject himself/herself multiple times throughout the course of the day. Replacement therapy is a preventive method so the Factor must be injected continuously and the constant presence of foreign Factor can trigger the body to create antibodies. The antibodies stop the effectiveness of the factors and can result in many complications. So far, the most effective solution problem is to use Factor VIII from pigs. However, this solution is also very expensive and carries the classic risks of transmitting diseases. Because of the necessity of the injections, many doctors recommend installing vein access devices that help make injections easier. However, this also leads to many problems with infections. Desmopressin, a man-made hormone, can be used to treat people who suffer from mild hemophilia. Desmopressin helps to release naturally stored Factor VIII and vWF, but its effects wear off if used too often. As a result, it is usually only taken before dental work or extremely vigorous activities. Antifibrinolytic medicines are pills that can be taken to help blood clot, but are not always very successful. Similar to Desmopressin, it is usually only taken in certain circumstances. As you can see, there are definitely treatment options available, but all of them have significant drawbacks.




 * <span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">The Design: **<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">This design focuses on the creation of a gel containing Factor VIII producing //E. coli// that can be applied topically to external cuts. The modified //E. coli// will respond to the inducer fibrin, which is released naturally when the skin is cut. The presence of fibrin will then trigger the expression of the LuxS gene that produces the LuxS enzyme. A-2 is produced by the LuxS enzyme and plays a role as a signaling molecule in the process of quorum sensing. Quorum sensing can allow the bacteria to "talk" to one another and cluster around the exposed skin, much like platelets. Quorum sensing is important in this design to ensure that there is a sufficient number of bacteria around the "active site" (cut) so enough Factor VIII can be released into the bloodstream. The Al-2 then binds to the LSR transport and is phosphorylated. The new Phospho-Al-2 binds to the LsrR repressor which activates the LsrR promoter. The Porcine Coagulation Factor VIII (from pigs) is then produced and then released into blood around the exposed area, enabling platelets to gather and a fibrin net to form. //E. coli// is generally harmless to humans and any bacteria that make it into the blood stream should be taken care of by the body's immune system.



<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">**Expected Results and Advantages:** If everything went perfectly, I would expect this design to provide a way for hemophiliacs to combat the problems concerning continuous bleeding from scrapes and scratches. This design was meant to be used as a portable "first aid" kit for hemophiliacs. When working perfectly, one could apply the gel to any bleeding scrape or cut and let the bacteria emit Factor VIII to aid in fast blood clotting. The advantages of this product would be its ease of use, its convenience, and its low risks. As opposed to replacement therapy, this process would not need the use of continuous injections and therefore helping to eliminate the chances blood transmitted diseases and infection. This process would also be <span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">effective for hemophiliacs that have developed antibodies to traditional Factor VIII that comes from human blood. This design utilizes the Factor VIII from pigs and is not affected by the antibodies produced by the human body. This product would be easy to use and efficient as it is site specific. If this product is successful, hemophiliacs will no longer have problems with external cuts and will hopefully require a fewer number of Factor VIII injections to live their normal lives.


 * Fibrin || Factor VIII ||
 * 0 || 0 ||
 * 1 || 1 ||

<span style="font-family: Verdana,Geneva,sans-serif; font-size: 110%;">This design would be further improved if there was some way to help clot internal wounds, as a major problem hemophiliacs suffer is joints swollen with blood from internal bleeding. Most of the solutions that I have considered involve placing bacteria directly into the bloodstream, where they could travel through the body and act almost like platelets, sensing cuts through the release of fibrin and then clumping to release Factor VIII in that area. This would solve the problem of having to constantly inject Factor VIII externally. However, bacteria in the bloodstream are currently not a probable solution as the body's immune system is not very willing to make exceptions to bacteria floating around in blood, even if they are "friendly". In order to further improve this current design, a kill switch would be useful to have, in case the bacteria that enter the bloodstream become harmful or the person's immune system is too weak to fight against them. One of the other major problems is the cost of the product, whether it is cost-efficient enough to be produced in mass amounts. Hopefully, the success of this design will help the thousands of people with Hemophilia A live a more fulfilling and enjoyable life, without the need to inject Factor VIII every day.



//<span style="font-family: Verdana,Geneva,sans-serif; font-size: 120%;">*Note that this design was geared towards people with Hemophilia A. The only difference between those with Hemophilia A and B is the type of clotting factor missing. Those with Hemophilia B lack Factor IV, which can be easily substituted for Factor VIII in this design. //

<span style="font-family: Arial,Helvetica,sans-serif;">Hemophilia Treatment Options: http://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/treatment.html

<span style="font-family: Arial,Helvetica,sans-serif;">Quorum Sensing Talk

http://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html

iGEM iGEM Kill switch http://2011.igem.org/Team:St_Andrews/switch

iGEM quorum sensing http://2009.igem.org/Team:Calgary/Lab/Quorum_Sensing

<span style="font-family: Arial,Helvetica,sans-serif;">Porcine Coagulation Factor VIII

http://parts.igem.org/Part:BBa_M11099?title=Part:BBa_M11099

<span style="font-family: Arial,Helvetica,sans-serif;"> Hemophilia General Information

http://www.webmd.com/a-to-z-guides/understanding-hemophilia-treatment

Nanotube Transistors for Lyme Disease http://medicalphysicsweb.org/cws/article/research/53845

Revolutionary Biosensor "Artificial Skin" http://www.sciencedaily.com/releases/2013/07/130708124423.htm

Brazilian pesticide sensor http://www.gizmag.com/pesticide-biosensor-brazil/27912/