Finding NEMO in the Sustainable Development Goals

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In my previous article, synthetic biology emerged as an extremely powerful tool that can help tackle some of the United Nations’ Sustainable Development Goals.

As a member of the 2020 University of Edinburgh iGEM team, I would like to exemplify how this can be done in practice using our project. 

iGEM is an independent, non-profit organisation involved in fostering advances in synthetic biology through education and collaboration, both of which are integral parts of the annual iGEM synthetic biology competition. 

Every summer, more than 6000 students from hundreds of different universities across the globe tackle everyday issues by using a variety of tools synthetic biology has to offer. Each team, that is as diverse in competences as it is in academic background, creates and innovates with the motivation of challenging the boundaries of synthetic biology while addressing burning issues. Besides contributing to solving those problems that are more often than not congruent with the SDGs, team members acquire a comprehensive skill set including scientific communication, project design, international networking, and resource and team management on top of the evident deepening of expertise in synthetic biology. 

The iGEM innovation programme strongly encourages students to tackle problems incorporating human practices, implementing ethics, sustainability and social justice into their project and making these characteristics key elements of the competition. 

Every year, the iGEM community witnesses great collaboration between the teams. Students at academic institutions from every corner of the world support each other throughout the competition. 

As a part of the 2020 University of Edinburgh iGEM team, I would like to share my experience participating in this exciting synthetic biology competition with the amazing Finding NEMO team. 

Finding NEMO is an acronym for Finding Nanoscale Elements, Micro- and Macromolecules and Oligonucleotides. While the full name is a bit a mouth full, the system’s purpose is quite straightforward. Finding NEMO, in its essence, is a cell-free biosensor for a wide variety of molecules that can be applied in several different ways. For the purpose of the competition, we have focussed on its use in sensing contaminants in water such as arsenic, pathogens and heavy metals. 

In terms of Sustainable Development Goals, we aimed to tackle SDG 6: Clean Water and Sanitation. To get an idea of the historical background of SDG 6 and the current progress with regard to universal access to clean water and sanitation, we talked to a former UNHCR-volunteer who was deployed in Congolese refugee camps following the genocide in Rwanda, and discussed how the lack of access to water and sanitation has catastrophic consequences.

How did you experience water contamination, and what are the direct consequences of a lack of access to water, sanitation and hygiene? 

Especially in the situations in which I have worked, in refugee camps where people lived in huts made from plastic sheeting provided by UNHCR and where they lived very close together, the consequences of lack of water, sanitation and hygiene were disastrous. In 1994, close to one million Rwandan refugees came across the borders into the eastern DRC in a very short period of time. There was no water, and no sanitation.  While some refugees managed to settle around the Kivu lake others had to move on as there was no room for such large numbers. UNHCR had to involve NGOs to bring purified water with big trucks which was a major undertaking given the size of the refugee population and bad roads. A cholera epidemic broke out very soon and tens of thousands of people died. This then caused another problem as there was no safe way to dispose of so many bodies and the only mass grave was 26 kilometresaway from the camps. Digging graves was also problematic as the volcanic rock made digging extremely challenging. The cholera victims from the camp I worked in were in the end buried under big piles of sand and not far away from where other refugees lived.  Then medical NGOs set up infirmary tents to try to save the lives of many cholera patients by rehydrating them intravenously.  The used needles were burnt in improvised incinerators. It was all an absolute apocalyptic scene. This was, however, a long way back, in 1994, and the UN and many other organizations involved in water and sanitation have been working very hard to improve things.

What are secondary, socio-economic consequences of a lack of access to water, sanitation and hygiene? 

Experts have pointed out that people who lack access to water and sanitation also tend to be affected by other forms of poverty, including income poverty, poor health, and low levels of education. 

When people live under poor sanitary conditions then of course their health suffers. When their health suffers they get weak and unable to work which gets them further into a socio-economic downward spiral. Therefore, action on SDG 6 can accelerate the achievement of other development goals.  Experts have also noted that taking action in the areas of SDG6  where there are particularly strong interconnections and interdependencies across SDGs can be especially effective – creating a ripple effect that improves the lives of human beings. A sustainable and just economy means one in which industrial activities do not come at the expense of the human rights to clean water and sanitation.

 How much progress has the UN made with regard to water, sanitation and hygiene so far, and especially since the UN committed to the SDGs in 2015? 

SDG 6 is about ensuring the availability and sustainable management of water and sanitation for all. A lot of progress has been made and many UN entities and NGOs are involved with SDG 6 in some way or another. However, a real challenge is often effective data collection and data consistency among sources, which is needed to measure progress. UN Environment, WHO, UNICEF, UN-Habitat, FAO, etc. all have a role to play. They work in equitable access to safely managed sanitation services, including hand-washing facilities with soap and water, safe treatment of wastewater, increase of water-use efficiency. A very important factor in this is however that we need to increase the level of participation of local communities in water and sanitation management etc. I work for an organization that works with UN Volunteers and UN Volunteers often work with local communities as it is all about capacity building, participation, inclusion and involvement.

What are the major obstacles to meeting SGD 6, and what can be done?

Of course the COVID-19 pandemic which has become a serious global health concern will definitely lead to social and economic fallout to some extent that is difficult to imagine or foresee. However, water and sanitation service providers can be instrumental in stalling COVID’s advance. For example, the Global Water Operators’ Partnerships Alliance (GWOPA) is an international network created to support water operators through Water Operator’s Partnerships (WOPs). These are peer support exchanges between two or more water operators, on a not-for-profit basis, with the objective of strengthening their capacity, enhancing their performance and enabling them to provide a better service to more people. GWOPA situates WOPs as an approach for localizing the SDGs and GWOPA’s Secretariat is positioned as the global convener, catalyzer, advocate and knowledge broker for WOPs.

Is meeting SDG6 before 2030 a realistic goal? 

It is very difficult to make any predictions as meeting these goals depends on so many factors, many of which are not foreseeable, such as the impact of the current COVID-19 crisis. It is expected that by 2025, 1.8 billion people will experience absolute water scarcity, and two thirds of the world’s population will be living in water-stressed conditions. Drought and water scarcity are considered to be the most far reaching of all natural hazards, causing short- and long-term economic, health and ecological losses.  Therefore, at all levels, it is essential to reverse the trend of overexploitation of the global environment. Exploitation must be managed within boundaries that maintain the resilience and stability of natural ecosystems, and allow for the natural renewal of resources. And furthermore, key to achieving the SDGs is localizing the approaches, peer to peer support and knowledge transfer, participation from local communities. Advances in technology for water purification, waste management, water resource management, etc. will of course also be major contributors.

This interview was very insightful and illustrated the importance of technological advances and involvement of local communities as well as peer to peer support and efficient knowledge transfer all of which we tried to implement into our project with substantial effort. 

Based on these commitments, we developed Finding NEMO, the first biosensing platform to operate cell-free and solely through transcription. By stripping back the material necessities, we made biosensing faster, cheaper, safer and more accessible.

Depiction of how the sensor works. Image credit: 2020 University of Edinburgh iGem Team

The framework can be subdivided into four main sections: signal input, signal amplification, signal processing and signal output. 

To understand the biology of the signal input section, it is important to understand the roles of transcription factors and riboswitches. These are molecules that regulate the amount of a protein that gets produced from its DNA, by modulating production of the intermediate mRNA. They do not act spontaneously; they are activated by other factors such as cellular signals, metabolites, or – of interest to us – environmental compounds. Different transcription factors bind different compounds, so we identified some that are bound and activated by the compounds we wish to detect in water.

More abstractly, if we want to detect compound A, we will incorporate a transcription factor into our biosensor that is activated following exposure to compound A. Consequently, the transcription factor will activate the production of mRNA. In a normal system, this mRNA is used to produce the protein, but our biosensor does not continue this far. Doing so bears a lot of advantages. It is faster, because the subsequent protein production is slow and is not necessary to generate a signal output in our system. Furthermore, the absence of protein products makes our biosensor safer. It avoids the risk of potentially synthesising toxic proteins. 

Besides traditional biosensing modalities, we also incorporated direct oligonucleotide sensing as potential signal input.

Following the sensing itself, the signal must be amplified by making many copies of the mRNA. Following this step, the signal is processed before outputting a fluorescent signal which was enabled by biomolecular logic systems.

Biomolecular logic is a burgeoning field of science, and has begun to make its way into the field of biosensing and diagnostics. One unique element of our project is the development of a novel, nucleotide based biomolecular logic system mediated by T7RNAP. Through this mechanism, the biosensor is able to process a predetermined interpretation of multiple sensing targets to give a single meaningful result – without the need for complex analysis or skilful interpretation. By integrating “hard-wired” processing, we aim to democratise the technology so that even non-specialists can use it. And by integrating biomolecular logic, we avoid being truly “hard-wired” or encumbered by the additional cost increment, or infringement on disposability of actual electronic hardware. 

The interpretation of the output is relatively simple: the biosensor will output a fluorescent signal, which will indicate the presence of a contaminant. Based on the colour of the signal, the user will be able to identify the contaminant respectively.

As with any product intended for in field application, a responsible design must be considerate of the environment it is used in. From its inception, our minimal system has been designed to leave an equally minimal trace on its surrounding environment. We understood that a crucial factor for most in-situ commercial biosensors is disposability. Test samples, any materials and any produced chemicals must be non-toxic and preferably completely biodegradable. Our cell-free design facilitates a minimal mixture to be adhered to small disks of filter paper which are completely biodegradable.

For our system to be the success we envision, we need to ensure that the science is open and accessible to all. Straightforward and reproducible construction enable any prospective researchers to quickly and easily get involved. Our minimal design makes this easier than ever, as all of our base components can be acquired commercially in a matter of days and for minimal cost. After that, construction itself is as simple as pipetting into a test tube!

Any successful product must also be economical. By operating cell-free and using transcription only, we minimise the need for excessive investment for construction of each sensor. Cell-free solutions are made cheaply through cell culture and can be freeze dried on substrates as simple as filter paper. The protein components of the system can be grown recombinantly on mass scale, and nucleotide components can be replicated indefinitely by processes such as PCR –  both for a very low cost.  

This sensing technology bears exciting applications: its ability to sense heavy metals, pathogens and other contaminants facilitates its application in water contamination and as an aid for the diagnosis of overdoses, viral, bacterial and parasitic infections, soil contamination and more. 

We are very excited to present our biosensor at the iGEM competition and are proud to have contributed a small part to tackling problems that are of highest priority for a healthy and sustainable future. 

Written by Fynn Comerford and edited by Ailie McWhinnie.

Fynn is a member of the 2020 University of Edinburgh iGEM team who have developed a cell-free biosensor that can detect a wide variety of molecules. Specifically, the team has focussed on its ability to detect contaminants such as arsenic, pathogens and heavy metals in water. Read more about the application of synthetic biology to the UN Sustainable Development Goals in Fynn’s article Synthetic biology meets the Sustainable Development Goals.

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