Team:TAS Taipei/Design

Human Practice - TAS Taipei iGEM Wiki





Human Practice Summary

What we discovered through our findings in policy and practice helped shaped the trajectory of our project. We gathered data from researchers, medical doctors, veterinarians, cataract patients, and public opinions to find out the best way to develop our project so that it can benefit as many people as possible.

Our Policy and Practice is separated into three categories, Research, Outreach and Impact. In the Research category, we collected and analyzed data from researchers, doctors, vets, investors, patients and the general public. This information shaped the direction of every part of our project, including the construct design, nanoparticle prototype synthesis and delivery, biological modeling and the development of a marketing plan for selling our final product. In the Outreach category, we educated the public and spread awareness of our cataracts project, synthetic biology and science in general. We also collaborated and communicated with two iGEM teams to help solve problems together. Through educating and raising awareness, we hope not only to get more people involved in finding a solution to cataracts, but also to get more people involved and interested in synthetic biology research. The final category, Impact, includes working with organizations and infrastructure that is already in place to actually help people who suffer from Cataracts. We have raised funds, through bake sales and other events, to donate to the Himalayan Cataracts Project, a non-profit organization based in Nepal. With the help of our business and economics teacher, we have also created a marketing plan and started discussions with several biotech investors about the possibility of getting our project to market.



Research


Professional Help

In order to improve how we develop our research and prototype we needed to get in contact with experts in the fields of eye surgery and cataracts research. Our first step was to contact eye doctors to discuss any problems associated with current cataracts treatment. Finally, while developing our project we realized that cataracts is a major issue in pets and other animals as well as people. As a result, we contacted local veterinarians to discuss what pet owners do when their pets contract cataracts. As our project developed, we needed more specific information regarding our genes of interest, cataracts development, and our delivery mechanism. We contacted scientists doing research similar to our own to get their opinion on our projects progress.




Contact with Eye Doctors

We contacted local Taiwanese eye doctors to ask them about cataracts surgery. Here is a list of the doctors we contacted along with the information they provided:

Dr. Wei-Chi Wu is a retina specialist and an associate professor at Chang Gung memorial hospital in Taiwan.

According to Dr. Wu current cataracts surgery methods are efficient and effective, but are not without their issues. Besides the issue of high cost of surgery, there can also be several different post-surgery complications such as infection, hemorrhaging, or secondary glaucoma. In regards to our project, he said one of the biggest issues we would face is non-invasive delivery. Currently, injections and incisions are the only methods for delivery because all current potential methods of noninvasive delivery either lack efficiency or induce with side effects.

Dr. Tsu Chieh Cheng is a optomologist at Chang cheng eye hospital in Taiwan.

Dr. Cheng points out that aside from possibly causing complications such as astigmatism, myopia, and hyperopia, cataracts surgeries have risks, for wound infections, dislodgement of lens, and massive bleeding during surgeries aren’t uncommon. He remarked that our project sounded very promising, but the effect the drug has on other parts of the eyes must be checked. Furthermore, he suggested us to use rabbits or dogs as animal models, because they can be observed more easily.


Contact with Veterinarians

Cataracts trouble millions of people’s lives as a result of aging and diseases; however, many pet owners come across the problem of their pets suffering from cataracts as well. To alleviate this problem, we investigated if the potential benefits of our solution for preventing and treating cataracts can be applied to domestic animals as well.

As we continue to develop our project with consideration for the application on other animals, we realize that the slight dissimilarities among the lenses of different animals must be accounted for. Therefore, we consulted with veterinarians at clinics around Taipei. We visited two veterinarian clinics, (Nicholas Animal Hospital and Tai Pu Veterinarian Hospital) and asked various others about relevant questions regarding the viability of our project solution. From the interviews we gained valuable insight on the eyedrops that pharmaceutical companies have developed to mitigate the cataracts in the lenses. One of the drugs developed is called Ocluvet(R) which we purchased and used in our experiments to compare to our treatment model.

Team members and Dr. 李國閔 from Nicholas Animal Hospital after an interview.



Science Researchers

Researchers’ firsthand knowledge, regardless of how many papers one reads on PubMed, provides a better understanding on the topic of research. Thus, in order to gain a better view of our project, we have contacted professional researchers ,via email, who have in depth knowledge on 25 hydroxycholesterol, which is the main candidate for the cause of formation of cataracts.

Dr. Jason Cyster is a professor of Microbiology and Immunology at University of California, San Francisco; School of Medicine.

Dr. Jason E. Gestwicki is an associate professor in the Department of Institute of Neurodegenerative Diseases at University of California, San Francisco; School of Medicine.

According to Dr. Wu current cataracts surgery methods are efficient and effective, but are not without their issues. Besides the issue of high cost of surgery, there can also be several different post-surgery complications such as infection, hemorrhaging, or secondary glaucoma. In regards to our project, he said one of the biggest issues we would face is non-invasive delivery. Currently, injections and incisions are the only methods for delivery because all current potential methods of noninvasive delivery either lack efficiency or induce with side effects.

Our questions were primarily focused on how 25HC works on the molecular level. We asked questions such as: what are the current researches conducted that uses 25HC? To what extent is 25 HC responsible for reversing protein aggregation? And what are effective methods for 25HC storage? Both professors gave thorough responses on these questions, which we then used to in our experiments. One response that was particularly helpful from Dr. Cyster was his suggestions on effective ways to store 25HC, in which he provided us with a recommended storage temperature. On the other hand Dr. Gestwicki provided us with two published papers that helped us understand the mechanism by which 25HC reverses cataract formation and this helped elucidate our understanding of 25HC.

Dr. Eric P. Lee, Senior member of Technical Staff at Maxim Integrated

According to Dr. Wu current cataracts surgery methods are efficient and effective, but are not without their issues. Besides the issue of high cost of surgery, there can also be several different post-surgery complications such as infection, hemorrhaging, or secondary glaucoma. In regards to our project, he said one of the biggest issues we would face is non-invasive delivery. Currently, injections and incisions are the only methods for delivery because all current potential methods of noninvasive delivery either lack efficiency or induce with side effects.



Public Opinion


Bioethics Panel

We hosted a bioethics panel, where we invited teachers from various fields to engage in a conversation about bioethics and thoughts on our project in particular. The reason for including teachers from different fields is to allow our project and the topic of bioethics to be discussed from different aspects. Since we did this at the start of our project, the opinions shared and advice given during the panel shaped the direction of our project.

Dr. Jason Cyster is a professor of Microbiology and Immunology at University of California, San Francisco; School of Medicine.
Dr. Jason E. Gestwicki is an associate professor in the Department of Institute of Neurodegenerative Diseases at University of California, San Francisco; School of Medicine.

Survey

During TAS’s Spring Fair we conducted a survey, from which we derived a general sense of how willing people are going to buy products that are produced by GMOs, and our eyedrops in specific.

Interviews with Cataracts Patients

We did interviews with two cataracts patients about their past experiences in different cataracts treatment, and extracted this information along with the responses from survey, and incorporated into some of the ideas in our marketing plan. Something in common that the two people we interviewed had was that they both suffered from inconveniences due to the lens options, which would either make one nearsighted or farsighted. Furthermore, complications due to the surgery varied among individual cases; one suffered from dryness and irritation of the eye, while the other had no complications at all. Nevertheless, both of them stated that the surgery process was efficient and effective; however, if given the choice to apply effective eye drops instead of surgery, they’d be willing to use it despite some may fear the idea of having nanoparticles in one's eyes.

Dr. Jason Cyster is a professor of Microbiology and Immunology at University of California, San Francisco; School of Medicine.
Dr. Jason E. Gestwicki is an associate professor in the Department of Institute of Neurodegenerative Diseases at University of California, San Francisco; School of Medicine.


Education and Outreach

Science is often intimidating to many, but with little explanation and some experience, it isn’t scary at all. Thus, aside from the goal to raise awareness of cataracts, the promotion of science and synthetic biology in particular, are also topics we aim elucidate. Here are a list of activities and programs that serve our purpose.


Kindergarden

Science is often intimidating to many, but with little explanation and some experience, it isn’t scary at all. Thus, aside from the goal to raise awareness of cataracts, the promotion of science and synthetic biology in particular, are also topics we aim elucidate. Here are a list of activities and programs that serve our purpose.



Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.


We designed some easy experiments to let the Kindergarten students try playing with. We did this for several times, and the kids loved it. The experiments were usually very simple yet demonstrates important scientific concepts, for instance, we teached them how to use the microscope, why light reflects through prisms, how static electricity works etc.


7th Grade

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Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.


For 7th Grade we decided to touch on synthetic biology more in depth, and therefore aside from teaching the 7th grade students the general idea of how synthetic biology works, we also introduced them to some of the basic laboratory techniques essential to synthetic biology. We conducted games where students had to identify RBS and promoters in order to test their understanding of the topic, and for the experiments they learned how to run gels and how to use the pipette.


IBSL

During the school year when we were brainstorming for potential project ideas, our team members were divided into several groups and gave presentations on those topics. This not only ensured thorough research on each topic, but also allowed us to receive feedback on those topics from both students and teachers. This really helped us decide on our final project idea.

Figure X. Full Construct.


Science Research Symposium

During the school year when we were brainstorming for potential project ideas, our team members were divided into several groups and gave presentations on those topics. This not only ensured thorough research on each topic, but also allowed us to receive feedback on those topics from both students and teachers. This really helped us decide on our final project idea.

Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.



We invited two science researchers to come to our school and give presentations on their research. This allowed us to learn how scientists conduct actual scientific research and also expanded our knowledge in other areas of science. Below are the science researchers that came.


Club

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Figure X. Full Construct.


iGEM Club

The iGEM Club was established X years ago, and the purpose of it is to raise awareness of synthetic biology in the TAS community. Club activities allow underclassmen to experience iGEM related activities and develop potential team members.



Figure X. Full Construct.
Figure X. Full Construct.


Collaborations with Other iGEM Teams

We collaborated with various iGEM teams, including NYMU, ASIJ, Tokyo technology, etc. This not only created opportunity for us to help each other with problems that each team had, but also allowed us to exchange ideas and stimulate creativity.



Figure X. Full Construct.
Figure X. Full Construct.
Figure X. Full Construct.


Impact

The cornea is the outermost layer of the eye which protects the eye by preventing entry of foreign materials, but this function also largely prevents drugs from reaching the lens (Gaudana et al., 2010). This problem has challenged researchers and driven them to search for a way to deliver drugs through the cornea and into the lens. Currently, the most promising ocular drug delivery method is using chitosan nanoparticles as drug carriers (Cholkar et al., 2013).

Figure C. Extracted and purified CH25H and GSR with 10x Histidine tag (in yellow) encapsulated in nanoparticles to aid delivery to the lens.

He expressed his interest and liking for our ideas, but suggested an addition of cost projections and a financial plan, for it would put us in a better position to engage with venture capitalists.

Nevertheless, we weren’t satisfied with a potential business plan from a venture capitalist, for we wanted to make a real impact in real people’s lives who were experiencing cataracts. Hence we considered our resources and did a bake sale at our school which gave us a total of $400 USD. In addition to the bake sale we also conducted a fundraising event during the spring fair at our school. We thereby achieved three goals: we conducted a survey for research purposes, raised awareness of cataracts by explaining our project to locals, and garnered donations from generous donors. After that, we donated funds that would be equivalent to the cost of 10 cataracts surgeries through a partnership with the Himalayan Cataracts Foundation.



Figure C. Extracted and purified CH25H and GSR with 10x Histidine tag (in yellow) encapsulated in nanoparticles to aid delivery to the lens.


Figure C. Nanoparticles containing GSH and CH25H embed into the cornea and degrade. The released proteins are then delivered to the cornea via a concentration gradient.


Citations












Prevention

GSR Eyedrop

Treatment

25HC Eyedrop

LOCS: 0      


Eyedrops




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