Team:TAU Israel/Human Practices

"Human Practices is the study of how your work affects the world, and how the world affects your work." Peter Carr, Director of Judging, iGEM foundation

Exploring The Problem

At the beginning of our group's journey – the first ever igem Tel Aviv University team, we have thought about many options regarding possible projects topics. Among other things, the issue of antibiotic resistance has been raised, which is a very broad issue and has been declared as a global problem by the World Health Organization a few years ago. The problem is aggravated mainly because it is difficult to find new antibiotics, while there is a continued development of antibiotic resistant bacteria.
In addition, the public is not sufficiently aware of the problem of antibiotic resistance and how severe it is, so we as a team have taken on two important goals: one is to find a novel method to fight antibiotic resistant bacteria and the other - to make science accessible to the public and raise awareness of this problem. We started researching the problem, read many articles, consulted with our instructors and came up with our cool solution...

Our Project - The Pyocin Solution

Based on Dr. Dean Scholl's article[1], we decided to use a protein complex called pyocin, which is made naturally by the bacteria Pseudomonas aeruginosa. We take the exciting system and "upgrade" it by changing the target to antibiotic resistant bacteria. During the year, we have been in touch with Dean and he advised us regarding several aspects of handling the pyocins.
Detailed description in Project Inspiration and Description page.

Consulting with Experts

Consultation with experts about our project and getting feedback was one of the most important things for us as a group. In February 2019, Prof. Christopher Voigt from MIT visited Tel Aviv University in order to lecture about his fascinating work. At the end of his lecture, we met with him and told him shortly about our idea. Chris was excited about this idea and said it has great potential.
During Chris's lecture, he presented a specific plasmid he is working with. Following our exposure to this kind of plasmid, we have read Prof. Voigt's article[2] and were inspired to decide to use the plasmid pAJM.1642, marionette, which is operated by Vanilic Acid inducer and has a kanamycin resistance gene. Its number of copies is medium.
We used this plasmid for the PrtN plasmid in our project (more plasmid's details in the Part Page ).

Developing The Product and Keeping Safe

Another great and helpful consultation we had was with Dr. Jonathan Lellouche, director of the Laboratory at the National Center for Infections Prevention and Antibiotic Resistance. We had a tour at this center, which is located in "Ichilov" Hospital in Tel Aviv. Dr. Lellouche told us about the center and its activity, its responsibilities and the state of the antibiotic resistant bacteria in the country. Each month, the Infections Prevention Unit receives a report from every hospital in Israel that contains information about new bacteria that acquired resistance, and Dr. Lellouche described to us the common bacteria strains in Israel, which are antibiotic resistant.
Among the bacteria described, one has caught our attention- the Clostridium bacteria, which is very contagious. We have decided to implement the information we got and to try and find a suitable tail against this bacteria with our software Tail-or Swift. When we ran the software, we found suitable tails with a grade of 219 and a 33% match (which is relatively high, ranking 20 out of thousands of possible tails). The virus Clostridium phage phiCT453A got the highest matching grade out of 3 possible viruses of Clostridium. In the future, we would like to develop our system with this tail, so it will be able to attack the Clostridium bacteria and by that, helping to fight an antibiotic resistant bacteria, which is very common in Israel! We would like to emphasize that we did not perform any wet-lab experiment with the Clostridium, since it is BSL2 and BSL3.
At the same meeting with Dr. Lellouche, we presented to him our project - PYO-PYO. We got some feedback from him and brought the in-body delivery of pyocins up for discussion. We emphasized to him that we know that systemic injection will be problematic because of an immunogenic reaction, and that we are looking for a solution. In addition, entering through the digestive system is problematic due to the acidity of the stomach, which will break down the pyocin - a protein. Therefore, we thought of a capsule for delivery. Dr. Lellouche emphasized to us that providing a protein element is one of the most difficult problems in the pharmaceutical world and many are trying to find a solution for it.
He suggested that we will consider local delivery by spray or ointment. Following the productive meeting with Dr. Lellouche - we set up a brainstorming group meeting, analyzed what was said and thought it might be a good idea considering the issue of using pyocins externally. Therefore, our future plan is to deliver the pyocins as a local and external treatment of ointment/spray.

Public Outreach

Making science accessible to the public has been one of the two main goals of our project. We have taken on the task of raising public awareness to the problem of antibiotic resistance and teaching the correct use of antibiotics to try and prevent the development of resistance when possible.
On "Researchers' Night", we took advantage of the shared platform of parents and children together in order to get the message across. We did this in an interactive way of lecture with a DNA experiment and interesting facts. At the end of the lecture, we performed a Kahoot quiz, examining the understanding of parents and children. In addition, we lectured at two different conferences in Haifa - once in the ISMBE 2019 conference and the other at the Technion Bar. Details about the lectures can be seen on the Education and public engagement page . In both lectures, we conveyed how serious the problem of antibiotic resistance is and raised public awareness. Through collaborations with various Instagram groups, we have published on social media the Worldwide iGEM project. With our monthly newsletter publications and news articles that were published about our team, we have been constantly updating the general public in the progress of the project.

References

[1] Scholl, Dean, et al. "An engineered R-type pyocin is ahighly specific and sensitive bactericidal agent for the food-borne pathogenEscherichia coli O157: H7." Antimicrobial agents and chemotherapy 53.7(2009): 3074-3080.
[2] Meyer, Adam J., et al. "Escherichia coli “Marionette” strains with 12 highly optimized small-molecule sensors." Nature chemical biology 15.2 (2019): 196.