- National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States (2014): n. pag. Centers for Disease Control and Prevention. U.S. Department of Health and Human Services, 2014. Web. 11 Sept. 2015.
- "Number (in Millions) of Civilian, Noninstitutionalized Persons with Diagnosed Diabetes, United States, 1980–2011." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 28 Mar. 2013. Web. 10 Sept. 2015.
A problem that the iGEM team had from the inception of our project was deciding how we could practically apply our system in a real-world setting. Logically, we looked for positions in the body where bacteria already live cooperatively with the body. Our research took us to the microbiome of the human digestive tract, where bacteria located in the gut facilitate digestion. This region appeared to present a strong possibility for the in vivo application of our system, as we could manipulate the gut microbiome to create an environment where our system could live symbiotically with other microorganisms in the human digestive tract.
Our manipulation of the microbiome would work in a manner similar to fecal transplants performed in patients suffering from infections of Clostridium difficile1. C. difficile often presents in patients who have previously been treated with an antibiotic regime that imbalances the gut microbiome and causes a condition of severe diarrhea and colon inflammation. C. difficile is difficult to treat with antibiotics, but fecal transplants help to restore a healthy gut microbiome in patients by exposing it to the healthy microbiome of a donor2. We imagined that our project could be implemented in a similar manner. Placing our therapeutic system in the gut would subject it to conditions where it can optimally function. In order for the system to work, the therapeutic E. coli must be placed in an area where it can sense changes in glucose. Additionally, placement in the gut would allow the therapeutic bacteria to be in close proximity to SGLT1 and SGLT2 channels found in the intestines. From here, the tripeptide drug, QSP, will inhibit the ability of SGLT1 and SGLT2 to absorb some portion of glucose into the bloodstream after meal times.
After talking about our project with the public, and learning their reactions, we realized that procedures seem more acceptable in the laboratory than when proposed as a future treatment method to potential patients. Specifically, in a series of debates we held at our local Maker Faire and the New York Hall of Science, we were confronted with some in the public who felt that synthetic biology isn’t natural based on claims that it goes against everything from natural selection to religion. These discussion made us realize that it is important to take patient’s wishes and expectations into account when developing a treatment idea. To learn more about patient expectations and the viability of our treatment proposals, the iGEM team met with the head of endocrinology at Stony Brook University Hospital, Dr. Harold Carlson.
Meeting with Dr. Carlson made us aware of aspects of our proposed treatment that we had not previously noticed. We learned that medication transitions for and treatment compliance in diabetes patients are difficult periods. Type 2 diabetes patients are often reluctant to begin treatments with oral medications. This reluctance increases as the treatment becomes marginally more invasive and necessitates the injection of insulin. Therefore, patients, he suggested, may feel extreme reluctance and trepidation towards a procedure that can permanently alter their microbiome. He suggested that the treatment regime that was least invasive and labor intensive would have the highest success rate. Otherwise, patients would opt for other, safe, widely-available diabetic treatments that exist on the market to manage their condition.
Synthetic biologists have a commitment to implementing their systems in a way that is safe and prevents contamination with the environment. A relatively small amount is known about the functions of the microorganisms in the microbiome. Implementing new bacteria into this environment has the potential to eliminate favorable microorganisms whose functions are still unknown. For this reason, the effect that a new synthetic bacterium can have on the environment of the microbiome cannot be predicted. Additionally, Dr. Carlson broadened our thinking to help us imagine conditions where contamination involving our system could occur. His primary concern was contamination of the system between patients with diabetes, and people who do not have diabetes. Thus, if people without diabetes are exposed to the therapeutic bacteria, they risk disrupting their own natural microbiome and being subjected to unnecessary treatment. Additionally, there is the risk that the E. coli in the therapeutic system can be released into the environment after disposal from the human body. Here, there is a very small and unlikely chance that it can outcompete other bacteria in the environment for vital resources.
Based on this discussion, we knew we had to go back to the drawing board and redesign the administration of our system in order to make it safer and more appealing to patients. After much subsequent research, we found inspiration in the 2011 Slovenia iGEM team’s work, who were able to incorporate synthetic bacteria into the bloodstream by protecting them with an alginate encapsulation. The microcapsule can be delivered subcutaneously to the patient. This treatment delivery would be no more invasive than one insulin treatment, and has the potential to deliver treatment for an extended period of time in the same manner as the gut microbiome delivery system. A microcapsule delivery system may be considered a safer option because it localizes the therapeutic bacteria in its own environment instead of having it free in the body. Additionally, E. coli can be tagged for degradation by the immune system with the addition of specific antigens in the event that the integrity of the microcapsule membrane is ever compromised. The microcapsule itself can also be designed in a way that allows it to be degraded on command in the event that treatment is no longer needed or discontinued. These features allow the treatment to be less permanent and act as a safety switch when applied in vivo.
On Campus Outreach and Education
Stony Brook Summer Research Symposium
Our team was invited to present the Stony Brook summer research symposium, an exhibition of student summer research. The team used this as an opportunity to create a preliminary version of our poster and practice our presentation skills for the jamboree.
Pre-College Institute Presentations
The Stony Brook Pre-College Institute, consisting of high school students from disadvantaged high schools, visited our lab to learn about iGEM and synthetic biology one afternoon. We were also able demonstrate some of the tools we use in laboratory protocols.
Admitted Students Day
Our team advertised the synthetic biology club to incoming freshmen as a part of Stony Brook University’s admitted students day. While talking to admitted freshmen about iGEM, we were also happy to offer tips and advice about getting into research, majors and picking classes at Stony Brook.
While educating the younger generation is important, we also wanted to spend time educating our peers. Our iGEM team founded and currently runs Stony Brook's first and only Synthetic Biology Club. This past semester, we presented at the annual Fall Involvement Fair. We were able to speak to hundreds of Stony Brook students about synthetic biology and our iGEM team. We also had people signup to join the club and stay informed.Our first general body meeting was a huge success! We had tons of interested students come down and spend a few hours learning! We think that the students had a great time and learned a lot. We plan on having meetings monthly, having different activities at each.
BIO202 & SSO101 Lecture
During one of the final days of class for BIO202: Molecular and Cellular Biology, we were able to present the idea of synthetic biology and iGEM to a class of about 500 students. These students were given a presentation on the meaning and applications of synthetic biology, the brief history and goal of iGEM, and the ways students can get involved in this emerging field. We were also able to present iGEM and synthetic biology for an SSO 101 event. Incoming freshmen are placed in themed residential colleges with one of them being SSO: Science and Society. Students must attend events which unite the residential college. At this event, our team presented our project, taught about the emergence of synthetic biology, and brought awareness to the rich research opportunities offered by iGEM.
Off Campus Outreach and Education
Cold Spring Harbor
During the months of July and August the Stony Brook iGEM team presented to hundreds of middle and high school students at the DNA learning Center in Cold Spring Harbor Laboratory. At each presentation, the students were introduced to an age-appropriate lesson on synthetic biology concepts and an overview of our project design. Many students were interested in learning about how to start an iGEM team at their high school; we provided them with the information needed to learn about how to start a high school team.
The Stony Brook iGEM team was proud to participate in Long Island’s first Maker Festival, an event aiming to inspire young people’s interest in science and technology. The team worked with young fair attendees to build synthetic circuits using pre-cut foam pieces representing promoters, a gene of interest, and a terminator. The Maker Festival was also used as an opportunity to spread synthetic biology awareness in the community.
Teaching at Wantagh High School
On June 3rd, members of the Stony Brook iGEM team visited Wantagh High School to educate high school students in biology and research methods classes about synthetic biology. Our presentation introduced the students to basic synthetic biology terminology, BioBricks, the iGEM competition and our project design.
Hall of Science
The Stony Brook iGEM team also went to the Hall of Science to teach children and their families about synthetic biology. We used games and some small scientific experiments to make families think about synthetic biology and why this could be perceived as a controversial issue.