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iGEM Competition and the University of Thessaly team: Is Amalthea Project The Future of Healthcare?

In the second part of the Greek iGEM teams article series that were successful and won a medal at the 2020 Giant Jamboree competition, that took place virtually due to the COVID-19 situation, I have reached out and asked some questions to the guys from the University of Thessaly.

Excited for the accomplishment of winning a gold medal🥇, I thought I should go forward and come in touch with them.

To say the least, I found their iGEM project insanely interesting!

That was mainly because some years ago, it must have been 2017, during my stay at the Weizmann Institute of Science in Israel, I had my lunch break in the lab of Dr. Ilana Kolodkin-Gal. My mouth-watering food obsession back then was hummus, which I was buying every single day from the “Hummus Place” as we were calling it in the lab, that was located right across the main gate of the Institute.

Anyway, my hummus addiction made me to digress a bit.

While I was enjoying my lunch, I see across a Nature Magazine (from the known Nature Journal) which I grabbed and started browsing through its pages.

I remember, still, encountering in the magazine’s pages a compelling research project taking place at MIT. Long story short, the project’s main goal was to bioengineer bacteria for the purpose of having a sensing mechanism that could secrete themselves biodrugs to patients’ gut environment.

But this could happen only when they were sensing that the patient had fever!

The idea behind the University of Thessaly’s project seems to have been inspired by similar scientific principles.

So, this Q&A session went somehow like this:

  • What exactly is the purpose of your project (Amalthea)?

Project Amalthea, essentially, aims through successive optimization procedures to provide, a clear example of translational Medicine (from bench to bedside) and a tangible indication of the potential of synthetic biology to therapy. We believe that Amalthea is the product of many innovative ideas and practices. It is not a medicine in the classic sense of the word. On the contrary, it is a microbe, a bacterium in particular, that has been genetically modified and programmed externally to recognize a pathological condition, in this case inflammatory bowel disease, hereinafter referred to as IBDs (intestinal bowel diseases), and which responds to the pathological signals appropriately, thus bringing a therapeutic effect to the patient.

Allegoric representation of Amalthea’s Horn📯
  • The inspiration and setup of your project came from ideas of previous IGEM teams. How did you mix up as a team your expertise, as well as the knowledge derived from previous projects by going one step further and making the Amalthea unique and yours?

Amalthea is, essentially, a genetically enhanced organism (GMO). We would say that it is a synthetic probiotic. We imagined a “smart” bacterium, which will certainly meet all the safety standards to the fullest, which can detect a pathological condition and at a subsequent time it will launch a chain of reactions in order to stop the course of the disease, alleviating its symptoms.

“Natural” biology has developed a particularly attractive and interesting class of proteins, the receptors, which are based primarily on the membranes of organisms and their role is to detect extracellular signals or stimuli and trigger an intracellular process of response and adaptation in these systems. In essence, receptors ensure and mediate the interaction and interplay of the microorganism or cell with their environment.

“Synthetic biology” exploits the products of “natural biology”, redesigns and modifies them in the context of external purposes, our own purposes, the researcher, the doctor, and the patient. In this case, we hypothesized that we could reprogram bacteria to detect and respond to a pathological condition by building an artificial signalling pathway to the standards of the TANGO GPCR system, an artificial pathway based on GPCR proteins, the largest family of receptors in organisms. Then, we meticulously and thoroughly immersed in the existing literature, we found some corresponding projects from the iGEM repository that dealt with this technology, and we tried to make a creative sorting and composition for the final formation of Amalthea. It is worth noting that very few teams had undertaken a similar project and we hope that we also added a little steppingstone for the teams that will follow.

  • What difficulties did you encounter throughout the project ( + the duration of covid -19 of course) and how did you deal with them as a team? 

The pandemic and the lockdown measures gnawed the available time we had, while at the same time depriving us of the benefits of direct live communication. However, in our work we were supported by our responsible teachers Mrs. Katerina Moutou, Mrs. Kalliopi Papadopoulou as well as advisors of the previous iGEM Thessaly team. 

Without the help and support of previous members we could not have done it.

  • Were there people who stood by you as supporters and mentors, and if so, what did you admire most about them? Were some tips crucial to the success of the project, and if so, what were they?

Yes, the guidance we had was a catalyst for the implementation of our project. The university gave us generous access to the laboratory equipment and the mentors gave us know-how and the pace to move on.

  • Do you see a relative response to the work done on this project in the environment of Greece, or even abroad?

Certainly, our work is “raw”, in the sense that it needs to go through different stages of optimization. However, we believe that it is an ambitious venture that reflects the developing processes that are currently taking place in this field. Essentially, with Amalthea and such related projects, we are launching a new era in the field of treatment, entering the stage of “metapharmacy”, if a term like this is allowed. Instead of prescribing drugs to the patient or injecting them with drugs or proteins that will circulate throughout the body, the patient receives a “smart microorganism”, in the form of a probiotic, which acts purposefully and biosynthesizes or secretes the drug in the affected area. We believe that as a concept it is something innovative. We certainly do not claim rights of ingeniousness, we just apply the toolbox of synthetic biology to build a solution and expect it to receive some recognition.

  • The presence of short chain fatty acids in the gastrointestinal tract has positive effects on the general health of both a healthy person and a person with idiopathic inflammatory bowel disease. Have you thought about how to evaluate the percentage of SCFAs that each person will need?     

Amalthea has an integrated feedback system. Lack of SCFAs due to intestinal disruption is a major diagnostic feature of IBDs. Amalthea detects this absence of SCFAs and starts a process of synthesis and consequently release of SCFAs, in order to compensate the shortfall. A small deficit leads to small production and a large deficit leads to higher production.

  • You made a rather strange but also smart – in my opinion – biosafety system, for protecting the environment from possible contamination with the genetically modified organisms you were working with. How did you come up with idea and what steps did you take to reach its final record?

“Kill switches” are a standardized and relatively simple biosafety methodology, which has been used by other teams in the past. We found the sequences we were interested in through databases and proceeded to “staple” them into functional gene units, first in silico and later in the laboratory. Essentially, we want the bacteria to act within the set limits we want and for doing that we must be able to control their course with an inductive neutralization system just in case.

  • The use of this artificial capsule as a live-time method for obtaining the necessary data from the internal environment of the gastrointestinal tract, is it believed to find widespread use by the general population? What is your experience now? (that is, what is the opinion of the general public that you have come in contact with and talked about through your actions?).     

A similar question was posed by the selection board during the competition. Indeed, there is a minimal risk of losing a scientific idea in the paths and reefs of conspiracy theories, ignorance, and the unconcealed fear of the uninformed public. In other words, some may be afraid that we are going to chip them. We shall see!

Capsule Image
Side view of the capsule: The capsule includes a semipermeable membrane, sensing bacteria, detectors (electrodes), Parylene-C membrane, kill-switch, RF transceiver, encapsulation PDMS, PCB, Battery, Microcontroller
  • I found your treatment system very interesting. What strategy did you design / follow to design the right strains to produce the beneficial short-chain fatty acids (butyric acid, acetic acid, and propionic acid)?     

Essentially the concept is to build a synthetic “metabolon” that will enclose all the intermediate metabolites required for the biosynthesis of SCFAs within bacteria. Practically, it is a polycistronic gene that will biosynthesize in the right order the enzymes that make up the biosynthetic pathway.

  • Through outreach events you managed to address young and older people, informing them about synthetic biology and what your iGEM project is about. What experiences did you gain through these collective actions of yours (what reactions did the people have, was there interest, how did they see it)?

What a joy it is transmitting knowledge and giving in general. It is very important for young children, kindergarten, and elementary-level school to get acquainted with synthetic biology’s broader terms, to grow up in a societal context according to the needs of the times and to not be afraid of science and innovation.

  • Finally, how do you feel about the gold medal and what are your aspirations for the future?  

Satisfaction and great joy! It was the culmination of our efforts and our hard work! Our team will continue for a 2nd year in a row in the competition with the same project intending to fix it, to develop it and to win again prizes in the contest!

What is your opinion about their work and success in the contest? Isn’t Project Amalthea a think from the future or it can be applied smoothly in today’s healthcare procedures, for those mainly who are in need❓