Project Description
Welcome to our Project Description. This is what we in iGEM Lund set out to accomplish in the beginning of our project. Our quite ambitious plan, to remidy toxic metal exposure, described below was made into reailty, with a few adjustements. If you want to know our design, head over to our project design!
The Problem
The recent technological evolution has raised our demand of electronic products, leading to an increment in industrial mining and mass production of electronics. The increase has led to a surge in redistribution of toxic metals (henceforth referred to as TMs), and thorough regulation has been implemented in developed countries to counter this [1][2]. However, even though we may regulate our contamination, there are many other ways in which TMs are being let out into nature. Volcanic eruptions, geothermal vents and microbial activity are responsible for a major part of TM redistribution [3].
TMs exist in several forms; organic, inorganic and ions, each have different characteristics. A common trait amongst them is the ability to bioaccumulate and disrupt metabolic activities by mimicking the structure of other compounds such as phosphates and amino acids [4]. Therefore, TM poisoning has severe implications on the human body. TM-poisoning is treated with chelation therapy, a last resort-treatment with several gruesome side effects. We saw a need for a viable and sustainable way of reducing the amount of TM-poisoning worldwide.
The three most common, widespread and troublesome TMs are arsenic, lead and mercury - each contributing to TM-poisoning in major parts of the world [5]. Being the health-freaks that we are in Sweden, you often hear about the dangers of TMs in your daily lives: “wash your rice eight times before cooking it to get rid of the arsenic”, “only eat fish once a week or you’ll get mercury poisoning”. Therefore, we started looking into ways of dealing with TM-contamination and poisoning.
Inspiration
In 2006, the iGEM-team from Edinburgh successfully made a biosensor that detects levels of arsenic in water wells. Through their project, they highlighted the calamity of TMs on our systems and provided insight regarding what awaits us in the future [6]. Later on, several teams within the iGEM competition worked on methods that employ synthetic biology to remove TMs from external sources such as soil [7], water [8][9], and fish [10][11]. Therefore, we saw the opportunities of a potential project focusing on a different aspect of preventing TM-poisoning.
We realized how extensive a filtration system would have to be if it were to be implemented in bodies of water in means of reducing the amounts of TMs before entering the human body, and therefore dismissed the idea. Instead, through conversation with experts we decided to focus on preventing TM-poisoning by bioaccumulation through synthetic probiotic bacteria.
Our Goal
Bacteria has lived alongside TMs on this earth for 4 billion years, and have therefore evolved a way to deal with TMs. Through accumulation proteins and chemical reactions they’ve managed to survive and thrive in contaminated areas. Our goal is to increase the bioaccumulation-capabilities of the known probiotic bacteria Escherichia coli Nissle 1917. We're focusing on the three TMs: arsenic, lead and mercury. For each heavy metal we’ve identified the pathways of transport and accumulation in means of overexpressing some of the necessary proteins involved [12][13][14]. We’re doing so by introducing three plasmids, one for each TM.
As our engineered bacteria is ingested it will adapt to the gut microbiome, absorb and accumulate TMs, to later be excreted through faeces, returning the TMs to the earth. In the earth the bacteria will cause no harm, in fact, it will most likely die due to it's lessened survival as it's wasting energy on creating our overexpressed proteins. It will be a preventative measure implemented in probiotic products to reduce the extent of TM-poisoning across the globe. Our product also lay ground for the development of filters to be used in bodies of water and elsewhere.
References:
- [1] Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ., “Heavy metal toxicity and the environment”. 2014-08-26, Taken from [internet]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144270
- [2] (SE) Kemikalieinspektionen, “lagstiftning” 2018-12-28, Taken from [internet]:https://www.kemi.se/prio-start/kemikalier-i-praktiken/lagstiftning
- [3] Masindi V., Muedi KL., “Environmental Contamination by Heavy Metals” 2018-06-27, Taken from [internet]: https://www.intechopen.com/books/heavy-metals/environmental-contamination-by-heavy-metals
- [5] Järup L., “Hazards of heavy metal contamination” 2003-12-01, Taken from [internet]: https://academic.oup.com/bmb/article/68/1/167/421303
- [6] https://2006.igem.org/wiki/index.php/Arsenic_Biosensor
- [7] https://2017.igem.org/Team:FAFU-CHINA
- [8] https://2017.igem.org/Team:Exeter
- [9] https://2016.igem.org/Team:UConn
- [10] https://2016.igem.org/Team:Lanzhou
- [11] https://2018.igem.org/Team:ColegioFDR_Peru/About
- [12] Yang HC., Fu HL., Lin YF., Rosen BP., “Pathways of Arsenic Uptake and Efflux”, 2015-09-22 Taken from [internet]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578627/
- [13] Mok T., Chen JS., Shlykov MA., Saier Jr MH., “Bioinformatic Analyses of Bacterial Mercury Ion (Hg2+) Transporters” 2012-06-02, Taken from [internet]: https://link.springer.com/article/10.1007%2Fs11270-012-1208-3
- [14] Hložková K., Šuman J., Strnad H., Ruml T., Paces V., Kotrba P., “Characterization of pbt genes conferring increased Pb2+ and Cd2+ tolerance upon Achromobacter xylosoxidans A8”, 2013-10-12, Taken from [internet]: https://www.sciencedirect.com/science/article/pii/S0923250813001873?via%3Dihub#