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People died from malaria since the beginning of this year.

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360000 People died from malaria this year

projected based on WHO World Malaria Report 20171

Despite joined investments of over 2 billion dollars each year, malaria continues to be one of humanity’s biggest burdens1. Armies of scientists, engineers and volunteers combine their efforts to reduce malaria burden each year, but as their quest continues, their goal remains ever out of reach. Why is that?

Malaria Deaths per 100,000. Age-standardized death rates from malaria, measured as the number of deaths per 100,000 individuals2.

In most industrialized countries malaria was eliminated or nearly eliminated. Present infrastructure and constant access to medical care and preventive measures allows efficient containment and limits disease spread. However, in developing countries, malaria elimination remains a challenge.

Synthetic Biology for a future without malaria

Currently used mosquito traps rely on a lure-and-kill mechanism. Common baits are CO2 or synthetic attractants. All these substances are volatile and quickly depleted, lacking sustainability in regions that have no constant access to preventive measures. Here we present a novel malaria prevention method that is based on synthetic biology. We take advantage of living bacteria steadily producing both bait and an insecticide readily available at any time.

Click on the Parts to learn more about their functions

The cyanobacteria S. elongates provides nutrients to sustain an E. coli co-culture. E. coli is engineered to produce odour baits and an insect toxin from the black scorpion, acting as both attractant and killing mechanism for malaria mosquitoes. To maintain a stable culture over extended periods of time, multiple soft growth inhibition mechanisms are employed, limiting E. coli growth instead of killing surplus bacteria, ensuring stability over extended periods of time.

Every environmental synthetic biology applications faces the problems of stability and containment.
Bacteria have a straight forward evolutional strategy: Grow faster than you die. This biology becomes a pitfall for elaborate systems designed to function well for a long time without maintenance. Environmental synthetic biology applications are practically impossible to implement outside of the laboratory.
Biosafety is best ensured by not releasing any GMO, how safe by design it may be. We solved both problems.

Mindfully designed hardware encloses the bacteria, elaborately balancing containment and a selective connection to the environment. Employing novel technologies, our synthetic biology is complemented with spatial co-culture separation, 3D-gel embedded culture, and a condition-responsive hydrogel to provide sustainability that exceeds all current environmental synthetic biology applications.

Hover over the S.H.I.E.L.D. to show details.

S. elongatus by iGEM Düsseldorf. Used with permission.

Nutrient production

Cyanobacteria such as S. elongatus convert CO2 into glucose using sunlight as energy source. As part of our collaboration with iGEM Düsseldorf, we employ a spatially divided co-culture of S. elongatus engineered to secrete glucose and our E. coli to enable sustainable production of lure molecules and insecticides over extended periods of time.

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Tight-sealed hardware

For improved producibility, the S.H.I.E.L.D. is composed of multiple interlocking parts. To protect the trap microenvironment and to ensure biosafety, all contact surfaces are sealed using durable NDR-70 sealing rings. Despite an easy technology, this exceeds common biosafety standards for storage and shipment of genetically engineered organisms.

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Self-healing hydrogel

A self-healing Polyammonium salt (PAS) hydrogel acts as reservoir for odour bait molecules and insecticides, and provides a surface for mosquitoes to land on. Bait molecules evaporate evenly from the surface of the gel. Mosquitoes take up the insecticide from here. If too much water evaporates from the S.H.I.E.L.D., the gel acts as a protective layer to prevent the bacteria culture from drying out. As soon as new water is taken up, the gel returns to its tasks.

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Biosafety and culture separation

A commercially available nano filter is sufficient to keep everything where it belongs. It separates the cyanobacteria compartment from the E. coli compartment underneath, as well as the encased genetically modified organisms from outside, and keeps the S.H.I.E.L.D. free of contaminations. Its simple production makes it economically fit for its task, contributing to the application’s industrial scalability.

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Dextran gel by iGEM Eindhoven. Scanning Electron Microscopy image taken by Ingeborg Schreur-Piet at Eindhoven University of Technology for iGEM Eindhoven 2018. Used with permission.

Tight-sealed hardware

To maintain an even distribution of cells, we employ the novel 3D gel-embedded culture developed by iGEM Eindhoven. E coli, which lifts the heavy-duty synthetic biology, is embedded in a dextran-based gel and kept stable for unlimited time. This way, no sedimentation takes place, and the gel prevents E. coli from dividing on top of our synthetic biology growth inhibition, ensuring maximum sustainability.

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References

  1. WHO. World malaria report. (2017).
  2. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117–171 (2015).

Funding