The Problem

Trimethylaminuria (TMAU), often referred to as “fishy odor disease”, is a metabolic condition characterized by the body's inability to oxidize trimethylamine (TMA) into odorless trimethylamine-n-oxide (TMAO). This deficiency results in the accumulation of trimethylamine, a volatile compound with a pungent fishy odor. When released through sweat, breath, or bodily fluids, this compound leads to the strong and unpleasant odor characteristic of individuals with TMAU.

The People

This rare and distressing condition affects those in multiple ways. Beyond the social challenges of dealing with an overpowering, stigmatizing odor, individuals with TMAU also encounter significant psychological issues. This includes heightened risk of mental health struggles due to the social isolation and anxiety caused by the condition. It is essential to understand the profound impact of TMAU on the lives of those affected to appreciate the significance of our project. TMAU is often a silent struggle, with many affected individuals feeling unheard and isolated.

E. esperance is not just a scientific endeavor but a vehicle for social change. We firmly believe that science should serve humanity, and our project is a testament to that belief—a journey driven not just by scientific curiosity, but by the profound desire to improve the lives of real people who inspire us every day.

Existing Solutions

While there is no cure for Trimethylaminuria, several treatment options and management strategies exist that people with this condition rely on. One of the primary approaches to managing trimethylaminuria is through dietary modification. This involves avoiding foods high in choline, trimethylamine oxide, and precursors like trimethylamine-N-oxide (TMAO). Individuals with trimethylaminuria are often advised to limit their intake of fish, eggs, liver, and other choline-rich foods, as these can exacerbate the condition. Instead, they may opt for a low-choline diet, which can help reduce the production of trimethylamine in the gut. Some individuals with trimethylaminuria may use acidic soaps and cleansers in an attempt to neutralize or mask the fishy odor. These products may have a temporary effect on the skin's pH, but they do not address the root cause of the odor, which is the accumulation and release of trimethylamine from the body. It is common for individuals with TMAU to engage in excessive showering as part of their efforts to minimize the characteristic odor associated with it.

Our Solution

Before embarking on our journey to develop E. esperance, we faced a pivotal decision as a team—where could a potential therapeutic solution have the most significant impact for individuals with TMAU? To make this decision, we conducted extensive research, consulted with experts, and engaged in thoughtful discussions within our team. It was essential for us to pinpoint the precise location within the body where our intervention could be most effective in mitigating the challenges posed by TMAU. Our research led us to a critical realization—the gut microbiome. This complex ecosystem of microorganisms residing in our digestive system plays a central role in many aspects of human health, including metabolism and the breakdown of dietary compounds. We recognized that targeting TMA at its source, within the gut, could offer a strategic advantage in addressing TMAU. Therefore, with a clear purpose and vision, we made the decision to design a genetically engineered probiotic. Unlike traditional medications, this probiotic is a type of beneficial bacteria intended for human consumption. It is meant to be consumed before meals, strategically positioned to assist the body in oxidizing the TMA byproducts that result from digestion.

We have designed and tested three biological devices with potential efficacy. These parts are designed to oxidize TMA into TMAO. To learn more, I invite you to visit our Engineering Success Page.

Our samples underwent comprehensive testing at the Colorado Children's Hospital, renowned as the official testing site for TMAU in the United States. This collaboration with experts in the field is a crucial first step in ensuring the safety, effectiveness, and real-world applicability of our approach. In addition to the collaboration with the Colorado Children’s Hospital, we have developed a protocol here at Florida State University.

The 2014 Paris Bettencourt team addressed Trimethylaminuria in their project. They engineered “BBa_K1403015”, a part that degraded TMA into TMAO. They used an indirect colorimetric assay as their proof of concept for the functionality of their part. We built upon their work by modifying their part and creating two more of our own to test. We employed the use of both tandem mass spectroscopy and HPLC as our assays of choice.

Our Mission

Our mission goes beyond eliminating the odor; it aims to improve the overall quality of life for individuals living with TMAU, addressing both the physiological and social dimensions of this debilitating condition. Throughout the course of our project, we've had the privilege of connecting with and listening to the stories of numerous individuals affected by TMAU. As these individuals reached out to us, it became abundantly clear that our project was not merely an academic endeavor or a pursuit of scientific curiosity. It evolved into something much more profound—a chance to create a tangible change in the lives of people who have been silently suffering for far too long. These stories are not just about the struggle with a foul odor; they are narratives of resilience, courage, and unbreakable spirit. We've heard about the daily battles, the challenges faced at school, at work, and in relationships. We've seen the tears and heard the desperate pleas for something that could bring relief. Our project is our response to these stories.

The Bradford Pear Tree

As you navigate our website, you might find yourself wondering why the abundance of trees and flowers? Throughout the duration of this project, we dedicated several months to carefully selecting both a name and a logo that would not only reflect our identity but also pay homage to the TMAU community.

Choosing the name was a deliberate process, and it eventually led us to "E. esperance. The "E" in "E. esperance" derives from E. coli, the bacterium we employed to showcase the feasibility of our devices. The term "esperance" serves as a synonym for hope. We believed that this combination of words encapsulated the essence of our project perfectly, as our primary mission has always been to instill hope within the TMAU community through innovative advancements in synthetic biology.

Designing the logo proved to be a challenging endeavor. At first glance, the most obvious choice appeared to be a fish, given that TMAU is often referred to as the "fishy odor disease." However, our team harbored reservations about using an image of a decaying fish to symbolize our project and the individuals it represents.

During a conversation with the owner of a prominent TMAU Facebook support group, who also happens to be a TMAU patient herself, we were introduced to the Bradford Pear tree. This particular tree boasts beautiful blossoms while emitting an aroma reminiscent of rotting fish. Remarkably, it has become an unofficial symbol within the TMAU community. In light of this unique connection, we decided to incorporate the Bradford Pear tree into our project's logo, as it held a profound significance for both our mission and the community we serve.

Beyond iGEM

Since the beginning, we've envisioned that our project has potential to live beyond the iGEM competition. We are thrilled to report that we aren't the only ones to agree with this sentiment. Florida State University has commited $1 million towards the new Institute for Pediatric Rare Diseases, and our project has been adopted as one of their first endeavors.