Oh My Gut (Therapeutics)

Project Description

Chronic Kidney Disease (CKD) is a type of kidney disease where the kidney gradually loses its function over time. The kidney's function is to filter out metabolic wastes and help discard them out of the body. However, when the kidney begins to lose its function, the ability to filter out metabolic wastes, especially uremic toxins also begin to decrease. These metabolic wastes, especially p-Cresol that is considered toxic to humans, begin to accumulate inside the body. p-Cresol accumulation in body is associated with cardiovascular disease in hemodialysis patients and also induces the deterioration of CKD.

We plan to engineer two types of E. coli Nissle, the first one to produce bacteriocin to kill one of the major p-Cresol producers inside the gut, a bacteria called Clostridium difficile and the other to introduce an alternative pathway for tyrosine by adding Tyrosine Ammonia Lyase so that instead of being metabolized into p-Cresol, tyrosine is metabolized into p-Coumaric Acid, which is not dangerous for humans. We also wanted to ensure that the E. coli will not produce tryptophanase to turn tryptophan into indole (which will be metabolized into indoxyl sulfate, another uremic toxin that is dangerous for humans), so we have decided to knock out the tnaA gene, which encodes for tryptophanase.

With Oh My Gut, we will be able to slow down accumulation of the toxic p-Cresol inside the body. Thus allowing patients suffering from CKD to be able to live a more comfortable lifestyle, and to lower the rate of getting cardiovascular disease.

Project Inspiration

During our brainstorming session, we have stumbled upon a paper reviewing a known derivative of the bacteriocin called closticin from Clostridium Butyricum, herein referred to CBM-B, is proven to kill Clostridium difficile effectively. By looking more into C.difficle, we have found out that C.difficle is a very “nasty” pathogen, which is responsible for the “uprising” of C.difficle infections in developed countries like the UK. Amazingly for us, we stumbled upon a research paper that told us all what this “nasty” C.difficle is responsible for, i.e. a major p-Cresol producer, which in itself is a very well studied uremic toxin linked to chronic kidney diseases (CKD) and chronic vascular disease (CVD). Digging much deeper into p-Cresol has left us with a single impression, it is a “nasty” substance made by “nasty” organisms, and through weighing the impact of p-Cresol on CKD, we decided that we have to reduce the production of this toxin as well, via pathway hacking. Why this thought then? Simply put, as one may not know, Taiwan is infamously known as the “Kingdom of Dialysis”, hence we decided on pursuing this area instead, by using bacteriocin CBM-B to effectively kill C.difficle and reduce the number of people who needs dialysis, most importantly, get rid the infamous title Taiwan has.

Contact Us

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Email: igem.ncku.tainan@gmail.com
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