Designing a Way to Help TMAU Sufferers

Posted bydavemontezPosted inFSU iGEMTags:, , ,

We are the 2023 FSU iGEM design team! We are responsible for researching, analyzing, and designing a solution for our topic of interest, which is trimethylaminuria, or TMAU. In the spring, we did intensive research to get a good understanding of the disease. TMAU is a disease that gives a fishy smell to those that are affected. This is caused by trimethylamine not being oxidized to trimethylamine N-oxide in the liver by the FMO3 gene. Trimethylamine is a smelly compound while trimethylamine N-oxide is not. When gut microbiota metabolizes L-carnitine, TMA is a by-product of this reaction. TMA then diffuses to the liver where it will be oxidized to TMAO. Since patients with TMAU have a defective FMO3 enzyme, TMA is not converted to TMAO and through perspiration, the smelly TMA leaves their body. Although there are other pathways to oxidize TMA in the body, the liver was where it was most abundant. 

While reading these papers, we had to change our mindset to one of a researcher. Anyone can read a scholarly article but do be a researcher, one must think beyond what’s on the paper. When reading articles, we ask ourselves why and how to have a better understanding of the information. Moving forward, we must apply what we understand from the article into a well-structured design. The better we understand the research, the better well-constructed solution we will have. When we had a concrete understanding of TMAU, we were able to move on to solutions. 

By the time summer began, we had come up with several possible solutions. We investigated each of them and ranked them to determine which solution was the best one. As a team, we decided to take an appropriate enzyme, supply it in a pill, and when the patient takes it, the enzyme will react in the small intestine which is where TMA is accumulated. It would react similarly to the Lactaid pill which reacts with lactose. An appropriate enzyme we chose was trimethylamine monooxygenase, or TMM, which happens naturally in a human body. After finding out that the stomach had little to no oxygen, the enzyme pill solution became more difficult. TMM needs riboflavin and oxygen for the enzyme to function. Supplying oxygen and the coenzyme would not work due to the difficulty of supplying riboflavin. Therefore, we moved on to another solution. 

Snapegene Viewer, a common tool used to design DNA plasmids. http://www.snapgene.com

For our second solution, we will work with a probiotic and we will still be using TMM because we found it to be the best enzyme to work with. Since TMM needs riboflavin and molecular oxygen to react, we assume FDA regulated E. Coli can supply the electrons for TMM to work in the small intestine. Normally E. Coli cannot convert TMA to TMAO therefore we need to modify it. To do so, we will design a plasmid that E. Coli will uptake and express TMM.  

Soon, we will hand off our plasmid design to build for them to run tests. Eventually we will be working closely together to have the best working plasmid and go through the engineering cycle a couple times. We are excited to put our design in the lab and hopefully be the beginning of a treatment for those with TMAU. 

Featured Photo by Louis Reed on Unsplash

37 thoughts on “Designing a Way to Help TMAU Sufferers”

  1. I don’t know rather cry or run and jump
    for joy. I’m so happy that someone is taking an interest on this condition. We
    Matter.

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  2. Hola chicos gracias por su gran trabajo para nuestra, Tmau comunidad y estamos por todo el mundo sufriendo está horrible enfermedad .

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    1. Es un placer ayudar a la comunidad Tmau tanto como sea posible. Estamos muy agradecidos por lo amable que ha sido la comunidad.

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  3. Christian, Gracias por el interés sobre esta enfermedad por ahora incurable, y a todos los que sufrimos las consecuencias permanezcan con fuerza y fe que algun dia viviremos como gente normal, God bless you all

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    1. The importance of this to sufferers cannot be underestimated and if some kind of treatment is found this could be literally be life saving and life changing as many in the community are literally living on the edge! Thank you and fingers crossed!

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  5. Hello really excited about this, regarding riboflavin, many of us already take large doses of riboflavin so would the original idea of TMM in a pill with a vitamin b2 supplement work? Thanks again

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  6. I am so happy about this news. There is hope that maybe those of us who suffer from this awful disorder will finally be able to live like normal people and not be shamed by others. May God bless those working on the cure.

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  8. oh god . It is what i have been praying for the last 5 years. I am in tears. I hope it reaaly works out and there will be a cure for tmau. I can’t wait to live like a normal person and be a part of this world not be suicidal. Thank you guys. Best of luck and again thank you

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  11. Hi, I’m from Brazil and I want to be a guinea pig, I have TMAU and I’ve tried everything, I smell like dead animals, burnt rubber, feces, garbage and vultures and flies follow me, help me. Could you contact me? And tell me which formula should I manipulate?

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    4. please share this group with us. I have been searching for a social media group to follow. I also am a sufferer of this horrible disease.

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  13. I’m from Africa but got a lucky chance to visit the US for short-term. I’d like to offer myself for research, as a terror survivor who developed this condition. Please I hope you accept, as I haven’t had any testing nor medical attention, as none exists in our developing country

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  14. sufferer of this since 8,44 now tired and in despair. when the treatment comes let me know Ive learned through the years not to get my hopes up high. thanks for your help and consideration

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  16. I am SOBBING. I can’t believe the day has came where someone finally cares enough to help us. I can’t believe this at all. Thank you so much for your research. You seriously have no idea how much this means to ALL of us. We didn’t chose to have this 😦 I just donated money to help your expenses on the SPARK website.

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  17. I am SOBBING. I can’t believe the day has came where someone finally cares enough to help us. I can’t believe this at all. Thank you so much for your research. You seriously have no idea how much this means to ALL of us. We didn’t chose to have this 😦 I just donated money to help your expenses on the SPARK website. You guys are wonderful wonderful people.

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  18. You have NO idea how grateful we all are as a community of sufferers. The daily shame we carry can often be too much to bear. You will literally save lives as a result of this research. If we are interested in volunteering for this remarkable research, is there a contact person we could reach out to?

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  19. I have a community full of those who have been diagnosed and who are struggling with malodor symptoms, from the UK and happy to be of use for any trials. Are community is vast. This is something many people don’t understand and have not been diagnosed with due to confusion, therefore there is more people suffering than we think, globally. This is myself included who was diagnosed in 2013.

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  24. I’ve had this almost my entire life. Possibly born with it. I am 33, going to be 34 this year. I’m looking forward to when this pill will come out. Any updates on the progress?

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  25. watching your child suffer is horrendous. We 1000000 percent need a cure asap. Ruining mental health. Routing for everyone everything crossed

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  28. L. Randazzo – I cannot express in words how uplifting this news is. It is wonderful that TMAU has been acknowledged. Many time

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