Team:TU Eindhoven/Society/Synenergene/Application Scenario


iGEM Team TU Eindhoven 2014

iGEM Team TU Eindhoven 2014

Application Scenario

Bacteria will be able to solve some of the biggest problems humans have to face currently. Some caused by us directly some indirectly. They can provide us with cures and treatments for diseases that most of us come in contact with during our lifetime. For example, bacteria that can function as a pancreas: sensing glucose and producing insulin within a human body. Alternatively, bacteria that can clean up leaked oil in an oil spill are a possibility. The possibilities are endless; to a certain extend.

Nowadays, the biggest constraint genetically modified bacteria encounter is their limited ability to survive under non-natural conditions, such as the harsh conditions in industrial reactors and the immune system in the human body. Since early 2014, it has been iGEM team Eindhoven’s goal to tackle this constraint. They aspire to deliver a system that would allow Synthetic Biology to fulfil its dreams; to be able to apply the great ideas in the real world.

We started out by developing a “plug-and-play” system, Click Coli, for bacteria by designing a Clickable Outer Membrane Protein (COMP). In the fall of 2014, the functionality of the system has been proven: using the COMP, any DBCO-functionalized molecule can be clicked onto the outer membrane of the bacteria. This opens up a whole new world of coating bacteria in a desired material or immobilizing the bacteria onto a desired material.

This is a great new addition to the chemical toolbox used for altering bacteria, but alone it does not solve a fundamental problem in utilizing bacteria. Many materials have to be tested on their compatibility and functionality before practical application of the Click Coli system outside of the lab environment. Furthermore, a kill switch has to be implemented for teams using Click Coli so that the coated, and thus extra resilient, bacteria can be controllably killed. Lastly, more tests have to be done on how a clicked on material affects the internal homeostasis of bacteria.

Before making the Click Coli system public property, team Eindhoven has decided to perfect the Click Coli system first. We made this choice because we did not want to take unnecessary risks by presenting to the world an incomplete system that enhances the resilience of bacteria. Also, we expect that our idea is more appealing if the Click Coli system comes along with its own safety measures. Luckily, the Technical University of Eindhoven sees the potential of our project and decided to sponsor our research. Furthermore, we wrote to several institutes, such as the RSC (Royal Society of Chemistry), to collect small grants. Using this and the facilities the university already offers us, we will be able to prolong our research.

We expect the research phase to be finished early 2016. The Click Coli system will then be finished: its functionality is proven and perfected, there is a broad knowledge on how a coating affects bacterial homeostasis and using that knowledge, procreation of the bacteria has been permanently halted. Furthermore, the genetic code of a kill switch is inherently linked to the system itself, so the risks are mitigated. We are convinced that now, the Click Coli system is ready to be released free to use for anyone.

We hope that many research groups will pick up at this point and will begin testing their own materials. At this point, team Eindhoven will leave its current formation and split up into daughter companies. These companies, as the name implies, are commercial institutes that will begin to develop their own product. Naturally, as they go into a commercial formation, they will lose the privilege of funding by the Technical University of Eindhoven. They will have to find their own capital through funding. In this paper, three possible daughter companies will be discussed, which are as follows:

  • A company which will create a product called Oil Munchers: bacteria that are able to survive in seawater and clean up spilled oil.

  • A company which will create a product called Synthetically Humane Bacteria: bacteria that are invisible to the immune system and can, similarly to the natural gut microbiotica, fulfill a predefined function inside the human body.

  • A company which will create a product called Water Purification Bacteria: bacteria that are present during the water purification process, while making it a lot more efficient and fast.

For each of these daughter companies, a paragraph is written below containing more information on the product, its stakeholders and future development. All these paragraphs are written from the perspective in 2016, when the Click Coli system has been fully developed.

Figure 1: schematic overview of the problem.

Water Purification Bacteria

In 2016, when iGEM team Eindhoven split up, one of its continuations was to create bacteria that would help the water purification process. Why take this path? The problem tree in Figure 1 answers that question.

In 2016, the world water problem still hasn’t been solved: Drinkwater is becoming scarce and a lot of valuable chemicals are lost in the process of purification. The purification process remains imperfect to say the least: there are a lot of filtration steps, which mainly are inefficient. Less harmful chemicals are added to remove the slightly more harmful ones. On top of that, the duration of the filtration is long.

We saw a simple solution to these problems: the multipotent bacteria, genetically modified to extract just the chemicals you want extracted and immobilized onto a filter using the Click Coli system. In order to seek funding, we sought out major water purification companies, such as:

  • Aquatech, who holds ‘innovation’ as one of the corner stones of their policy.

  • Ahlstrom filtration, one of the leading companies in fiber engineering

  • GEA filtration, who specializes in the engineering of membranes for nanofiltration.

Getting the financial support done was quite the task, but a few companies were willing to support us if in return, they got rights to the technology. In 2017, the real work starts.

We theorize that creating the bacteria and implementing them in usable filters is going to be the “easy” part. Three years of research will result in a viable product in the year 2020. The real challenge is in getting it implemented in the actual water purification systems, due to strict regulations. It is only after years of safety testing and trials, that the general public allows GMO’s to filter their drinking water.

Hopefully, the acceptance will be sped up by the facts that:

  1. The water purification bacteria are much more efficient.

  2. They are immobilized onto a filter.

  3. The Click Coli system comes with a working kill-switch.

We predict that eventually, the general public will accept the newer, more effective technique, even if they hold their conservative reluctance. Increasing the general knowledge of Synthetic Biology is an important factor in this matter. Everything considered: testing and trials, decisions on new regulations and general acceptation of the product, it will take until the year 2025 before the water purification bacteria first make their appearance in a water purification plant.

Figure 2. Stakeholders

Oil Munchers

Munchers d’oil Inc. is a company that widely produces products in which bacteria are incorporated. These bacteria are able to survive in seawater and can clean up spilled oil. The products can come in different sizes, dependent on the size of the spill. The product can be placed directly into the ocean or can it be embedded on ships or oil pipelines. The product can be used for approximately 12 hours, after which the used bacteria can be replaced with new bacteria.

The company started in 2015 and now has a sizable backbone of employees. The company has connections with other big companies like Shell but also other connections with for instance repairmen, engineers, oil distributors, suppliers and customers. A clear overview is shown in the stakeholders map in Figure 2.

Figure 3: Schematic overview of the problem.

Due to a lot of oil spills in the past 5 years, the company made a huge increase in popularity and success. This is shown in the problem tree in Figure 3. The future development of the company would be for small scale usage, such as oil removers at home or in offices. This should be ready to use in 2020.

Synthetically Humane Bacteria

In 2016 there are still a lot of diseases due to organ failure. Bioengineered machinery is not a permanent solution and stem cell therapy is not an outcome yet. It progresses far too slow due to the complexity of the human body. There are still many diseases that could benefit from organ replacement. The solution for these problems would be the use of bacteria to replace the organ, but the human immune system remains a problem. Our solution is to put a DNA coating on the bacteria using our Click Coli system. This coating shields the bacteria from the immune system so they can perform the needed function.

For funding we searched for biochemistry companies:

  • Bio-Rad: One of world’s largest companies for innovative tools for life science research and diagnostics.

  • New England Bio Labs: large Research Company in the field of Molecular biology.

These companies thought that our idea had a lot of potential, so after some discussion they are willing to support our idea. In 2017 the real deal starts. In 2 year the idea has been realized in the lab and is ready for the first animal trials. Around 2021 the animal trails will be done and human trails already have started. After that the hardest part starts, people have to accept the idea of GMOs inside their body. The general acceptation won’t be easy. Eventually people will accept it because it is a solution for people who else would be hopeless. Around 5 years later the whole idea of GMOs performing an organ function will be accepted.

iGEM Team TU Eindhoven 2014