Team:Tuebingen/Safety

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Short Safety-Overview

We...

  • chose a non-pathogenic chassis
  • chose parts that will not harm humans / animals / plants
  • substituted safer materials for dangerous materials in a proof-of-concept experiment
  • recommend including an "induced lethality" or "kill-switch" device for future use

Safety Measures

Would any of your project ideas raise safety issues in terms of: researcher safety, public safety, or environmental safety?

All our work is supervised by PhD students, PhDs and professors of our university who are very experienced in laboratory work and are currently working at the Interfaculty Institute of Biochemistry (IFIB). Their expertise reaches from genetics over molecular biology to structural biology. We document our work in our laboratory notebook to enable replicability. Our project does not pose any dangers to researchers or the public: we are following widely used laboratory protocols in an appropriate laboratory facility (biosafety level 1 laboratory, S1), as requested by German law ("Gesetz zur Regelung der Gentechnik (GenTG)", German Gene Technology Law).

Joining regular briefings concerning laboratory safety is an essential element of our education at the University of Tuebingen. In addition all members of our team heard a special talk about biosafety. The organisms used in our project, namely Escherichia coli and Saccharomyces cerevisiae, are well-known and considered safe. These organisms are specifically optimized to not carry out any pathogenic, toxicogenic, or colonising activities and due to the harmless nature of our parts we do not foresee any security concerns. In case of success in yeast, we try to test our system in higher eukaryotic cells, such as MEFs or human cancer cell lines. We do not plan to experiment with any other organisms. Our project is intended to be used inside the laboratory. We are working at a S1 laboratory, which implies several methods for guaranteeing safety to researchers and environment are constantly enforced but research is limited to well known and nonhazardous species.

What is the goal of the project? What will the engineered organisms do?

Our yeast cells, equipped with both, a biosensor to regulate gene expression, and our memory-module, will be put to use according to the necessities of the biosensor. Our memory-module will, upon activation and swift subsequent inactivation, excise a stop cassette from a portion of the population, according to the activity of the biosensor. The ratio of yeast cells with and without stop cassette will be a quantitative measure of the activity of the biosensor at the time of memory-module activation. Yeast cells without stop cassette will express a marker protein (GFP or Luciferase). The readout may occur at any point after the activation.

What risks does your project pose at the laboratory stage? What actions are you taking to reduce those risks? Do any of the new BioBrick parts (or devices) that you made this year raise any safety issues? The organisms we are working with are exceedingly well characterized and not known to pose danger to either humans or the environment. The same is true for the DNA fragments we use in our system. These organisms and recombinant DNA reagents are classified S1 according to the German Gene Technology Law (GenTG). Our experiments are performed under S1 conditions. These conditions include the usual safety features of wearing laboratory coats and rubber gloves, sterilizing waste, regularly disinfecting the workspace, etc. We have designed different BioBricks and none is found toxic or dangerous by any means. We re-used parts from 2013, which are also not toxic or dangerous. All of the parts we use are not known to have any harmful effect on humans or other organisms.

How would your project be used in the real world?

We do not intend any direct applications outside the laboratory. Any use as consumer products or in any small device is conceivable, but not intended.

What risks might your project pose, if it were fully developed into a real product that real people could use? What future work might you do to reduce those risks?

In a fully developed device neither the release into the environment, nor the contact with humans could be ruled out with 100% certainty. Such a device could implement a "killswitch" (to ensure that any cells released by accident would quickly and surely perish without access to required conditions that are only available in the laboratory). Also, the GMOs are held under physical barriers to the environment. A fully developed safety-approach would have to be part of any following project, concerning real world application of our foundational advance.

Do you have any other ideas how to deal with safety issues that could be useful for future iGEM competitions? How could parts, devices and systems be made even safer through biosafety engineering?

Parts that are able to induce cell death (apoptosis or autolysis) could be expressed under promoters that are activated in an uncontrolled environment as opposed to a laboratory. A huge amount of examples for these so-called kill-switches was designed by the iGEM community and is now available in the registry (see for example 2011's team of UCL London and the 2013’s BGU Israel's iGEM-team "Programmable Autonomous Self Elimination").