Dr. Lindner is a research director at the French National Institute of Health and Medical Research (INSERM). He was also an IGEM team advisor in 2014 for the Paris Bettencourt team. One objective of this 2014 team was treating Trimethylaminuria(TMAU).

Dr. Lindner expressed his excitement for the continuation in research of Trimethylaminuria. He expressed the importance of further research for this community in need and was more than willing to help our team. Dr. Lindner shared with us the ways in which their team connected with the TMAU community and learned the stories of TMAU patients. This included social platforms such as Reddit, and The Mebo Blog. These two social platforms were great tools for our team to hear the stories of TMAU patients that have been publicly posted.

Furthermore, the most beneficial patient platform Dr. Lindner provided was a website called Rareconnect. In Rareconnect, TMAU patients have created their own community. This community is a safe place where people can share their own stories, give advice to other patients, or post at-home remedies that they believe have worked for them. Our team wanted to use this platform in a respectful way to share our project and give hope to this community.

Dr. Wood is the Labratory Directory of Colorado Children’s Hospital in Colorado which is one of two sole TMAU testing centers in the United States.

During our meeting with. Dr. Wood, our team discussed the process of being tested for TMAU, which includes: the analysis of a urine sample, which is over-night shipped to Colorado Children’s Hospital, to test the ratio of TMA to TMAO. He explained that in a healthy human, the ratio of TMA:TMAO is typically 10%:90%, and any ratio that has a greater percentage of TMA is where symptoms of TMAU begin. This also answered our teams concern as to why there are different levels of symptoms. As the ratios can vary, some patients may experience minimal symptoms when the concentration of TMA is only slightly greater than 10%, or may experience much more extreme symptoms if the concentration is much greater percentages than 10%.

Dr. Wood then put us in contact with a, then, master’s student, Jillian Kirk, whose thesis was on TMAU and the patient experience. Which will be seen later in the timeline, Jillian Kirk offered invaluable information regarding the emotional states of these patients, as well as survey numbers to show how rare TMAU and TMAU testing is.

Dr. Wintermute is a Ginkgo Bioworks Employee, Synthetic Biologist, and former iGEM advisor.

Our team met with Dr. Wintermute for various reasons. One of the main reasons was that Dr. Wintermute was a member of the 2014 Paris Bettencourt IGEM team, just like Dr. Lindner. In this meeting, our team discussed the necessary factors to keep in mind when choosing an enzyme for our probiotic. Dr. Wintermute advised our modeling personnel to research enzymes who do not require energetic cofactors as well as enzymes that could survive in low oxygen environments. The warning of low oxygen was a thought our team had to keep in mind if the small intestine had a low-oxygen concentration. However, in a future meeting with Dr. John W.K. Oliver, Vice President of Research and Development at ZBiotics, our team learned that a low-oxygen environment isn't necessarily the case in the lining of the small intestine. Another model we discussed was the efficiency of the trimethyl monooxygenase (TMM) enzyme breaking down the TMA, and a model for the measurement of the decrease in TMA levels. The advancements and answers to these modeling questions can be seen in the "Models" section of "Engineering".

In this meeting, our team also discussed with Dr. Wintermute how this project is good for the world and can benefit a community desperate for help. Similarly, we discussed the quickest and safest ways to get this treatment to the patients in need. We knew there was a part of the drug developing process that makes it unprofitable for pharmaceutical companies, therefore, we needed to find a way to make this step cheaper. This problem would later be solved by our team learning to go the route of a probiotic rather than therapeutic.

Jillian is a certified Genetic Counselor at AdventHealth.

Jillian was another individual who was crucial in connecting our team to the TMAU community support groups. As stated earlier, at the time when our team contacted and held an interview with Jillian, she was a master's student under Dr. Wood. She described the biggest request of this group, relief. Any sort of relief, whether it be as big as a full-blown cure to as small as making the health care system aware of their disease. Those suffering from TMAU are desperate for any and all type of progress as no research has seemed to find any way to treat this disease.

As a part of her thesis, Jillian created a detailed survey for people who have TMAU or suspect that have TMAU to fill out. Despite her platform, she was only able to obtain less than 100 responses, and of those 100, only 20 had been tested for TMAU. These numbers not only show the rarity of the disease, but also the pure lack of testing due to price or inconvenience or lack of knowledge. Increased awareness of this disease become even more important after this interview as there is not only a lack of knowledge among physicians, but also a lack of knowledge among the general public, who might suffer from the symptoms of Trimethylaminuria, but are not be aware of the resources available to them.

Karen is a Patient Suffering from Trimethylaminuria.

Karen described to our team the horrors she has experienced living with this mentally crippling disease. She told us how she would be harassed on public transportation, as people would spray perfume towards her, and was forced to find jobs that required her to be outside. She also had to make significant dietary changes based off of tips other people who have TMAU stated help reduce the smell, which only helped to a certain extent. Other consequences in her life as a result of having TMAU is that she has been forced to sleep in a separate room from her husband and must leave windows open at all times in their house. This is not Karen's fault! Most people would be clearly blaming TMAU, however, when Karen approached medical professionals for help, she was insulted and told all she needed to do was shower. No matter how strong you are, hearing a doctor disregard your pleas for help and being told to simply take better care of your personal hygiene cannot be easy. But Karen has stayed strong. No matter how many obstacles Karen has faced, she has persevered.

It is this perseverance by Karen and all TMAU patients that further inspired our team to truly help this community. During this meeting Karen expressed that she spoke for the entire TMAU community when she says that they will take anything that will ease their symptoms and that they are grateful for the work our team is conducting

Ms. Kristy Anderson is a social work faculty member at Florida State University.

Our team met with her to discuss what our team can do to help TMAU patients apply for disability benefits. We felt the need to look into disability benefits after hearing stories of patients being fired out of their jobs or forced out of living establishments. Disability benefits would be another aid for TMAU patients.

Ms. Anderson explained to our team that for a disease to be classified as a disability, it has to be diagnosable and a life-long condition. This information meant disability benefits was definitely a possibility for TMAU patients as TMAU is both diagnosable and a life-long condition. After hearing this, our team asked Ms. Anderson who would be valuable stakeholders to further ask insight about this process.

Dr. Whittington is a member of the Florida State Department of Biological Science Faculty.

Our team decided to meet with Dr. Whittington to discuss the possible procedures for quantifying the levels of TMA. This was a major priority for our team because demonstrating with data that TMA levels drop after the ingestion of our probiotic. The literature had proposed high performance liquid chromatography, or HPLC, as a possible candidate to measure TMA. Dr. Wittington agreed with our team's initial procedure for the testing of the level of TMA. Dr. Wittington was very kind in showing us the HPLC machinery available to use at the Florida State University and discussed with our team the specific procedures for using the technology.

Dr. Nagpal Florida State University College of Health and Human Sciences Researcher.

Dr. Nagpal conducts extensive research regarding the gut microbiome. For this reason, our team believed it would be extremely beneficial to discuss with him our design. In this meeting, we discussed the viability of using an anaerobic chamber to simulate the small intestine. The use of an anaerobic chamber would be useful to test the efficiency of the TMM enzyme oxidizing TMA in an environment with little to no oxygen. Dr. Nagpal confirmed the idea that the concentration of oxygen in the gut microbiome is exceedingly dependent on the exact area of the gut in which the probiotic will target. Dr. Nagpal also showed our team how to operate an anaerobic chamber, the specific model of the chamber, and how it purges oxygen from its environment.

Mr. Edmunds is a Florida State University Licensing Manager.

Our entrepreneurship/implementation team spoke with Mr. Edmunds to understand how our team would handle the commercial market after our probiotic proves to effectively oxidize TMA. After this meeting, our team understood that 5-10 years down the road, a patent for this project would be needed, and conversations with manufactures and distributors would ensue. Mr. Edmunds reinforced our idea to produce a probiotic rather than a therapeutic drug. He explained the importance of looking for partnerships in the fields of production and distribution. This meeting was a very important piece of our entrepreneurship plan of action. Our full entrepreneurship layout can be found on the "entrepreneurship" tab.

Mr. Lickson is the Director of the North Florida Innovation Labs and has extensive experience working with the Food and Drug Administration (FDA).

Our team met with Mr. Lickson to gain a further understanding of the best path to take in regard to marketability of our product. Another important takeaway our team had after this meeting was how to approach (FDA) in a matter that would lead to fastest and safest path of getting our product to the TMAU community.

Our team now finalized that our probiotic pill would need to be classified as a probiotic, instead of a therapeutic drug. This is because probiotics contain less regulations by the FDA than therapeutics. Not only do therapeutic drugs have to be prescribed by a doctor, but they must undergo years upon years of testing before a company could even think of distributing to those in need. However, probiotics are deemed safer and require less rigorous testing trials and therefore can reach the patients in less time.

Mr. Hollimon is a Patent Attorney and well versed in Intellectual Property Law.

Our team met with Mr. Hollimon to understand the intricacies of the patent process as well as the classifications of intellectual property. From this meeting our team learned we would potentially be able to patent the method of production of our probiotic. In addition, we learned there could be an additional patent of its method of use. Mr. Hollimon advised our team to keep the potential patent novel, useful, and non-obvious. This meeting was another important piece of the building of a strong entrepreneurship aspect of this project.

Dr. Tomko is a Florida State University College of Medicine Associate Professor.

Our team felt the need to meet with Dr. Tomko to ensure the viability of our model designs. Dr. Tomko completed his graduate studies in pharmacology at the University Of Pittsburgh School Of Medicine’s Drug Discovery Institute, where he became familiar with modern drug discovery and development. During our meeting, Dr. Tomko stated to our team that our designs seem feasible. In addition, Dr. Tomko provided insight on E.coli Nissile 1917 and how it could function as an improvement to our initial iteration of designs.

Dr. Oliver is the Vice President of Research and Development at Z-Biotics.

ZBiotics is a company that used genetic engineering to develop a probiotic drink that adults can take prior to a night of drinking and will lead to the absence of a hangover the next morning. With our project being the development of a probiotic, we felt a desire to meet with members of ZBiotics.

In this meeting, we discussed our concern with oxygen concentration in the small intestine. However, Dr. Oliver said that there is ample amount of oxygen for our enzyme to oxidize TMA into TMAO. He explained our team must consider the turnover rate of the TMM enzyme as well as the concentration of blood volume to enzyme concentration in our testing trials. Other key insights Dr. Oliver provided with his knowledge of probiotics was to keep in mind that our probiotic would be competing against the uptake rate of the small intestine. We also discussed the aspect of liquid vs pill when thinking about the marketability of a potential product. Dr. Oliver expressed his favoritism towards a liquid for various reasons including: "Pills have negative existing relationships with many people, and many volunteers involved in trials favored drinks rather than pill capsules."