Noise, in electronics, is an unwanted disturbance in an electrical signal. On the other hand, in information theory, noise is considered to be the opposite of information. But what about noise and stochasticity in biological systems?

Noise permeates biology on all levels, from the most basic molecular, sub-cellular processes to the dynamics of tissues, organs, organisms, and populations. Due to biological noise, it is mostly impossible to determine with absolute certainty how a system will evolve from a specific initial state. The stochastic fluctuations in the level of cellular components can be caused by multiple factors. They can roughly be divided into two categories: intrinsic and extrinsic. Intrinsic noise refers to the stochastic fluctuations within the system under consideration, usually caused by the inherently probabilistic nature of the underlying biochemical reactions. The stochastic processes outside the system under consideration may serve a source of extrinsic noise.

At first, synthetic biologists considered stochastic gene expression an important obstacle to overcome. Nowadays, it has arguably become one of the main insights contributed by the discipline, since it reconstructs our comprehension of why, how and when specific genes are expressed. Within synthetic biology research, the use of the term noise often refers to stochastic fluctuations which can potentially have a functional status. For example, with synthetic biology pursuing the re-organisation and control of biological components to make functional devices, biological noise can be a source of inspiration and a field of observation for scientists in order to design new systems that exhibit the desired properties. Another way to approach biological stochasticity as a functional tool, is by considering it as an accelerator of the pace of evolution.

However, despite the positive effect of biological noise in the field of synthetic biology, there are cases where the systems being designed must be very precise. One such example is the system our team has designed this year. The decision-making in the system we propose in our project is based on multi-prismatic stimuli which have different weight and importance for the final result. With our system based on data collection and evaluation biological noise can lead to false results and be a problem for making the final decision.

This is why our team during the Aegean Meeting, organised by iGEM Patras, gathered many Greek iGEMers and organised the following collaboration. Wanting to observe noise in biological systems and in which cases it can be a problem, we organised the following game. Twenty iGEMers were placed in specific positions to form a square and each of them was given three circular cards of different color, one red, one green and one blue. Each time a member of our team told the participants a specific word and then they had to pick up the card with the color they thought matched the word they had heard and place it above their head. Their decision shouldn’t have been influenced by what color the other participants had picked. We took a photo of how the square was shaped in color for each word that was heard. The technique we followed was simple. At the beginning we told the participants apparently 'simple' words that clearly express one of the three colors. For example, the word 'fire' would obviously be represented by the color red for most participants. But then we moved on to much more complex words, much more abstract, where the choice of color is purely subjective and is not influenced by the physical properties of the idea or the object. The result for each word is shown below.

Having now received the photos in our hands we were ready to do a little statistical analysis of the results and draw our conclusions about the noise. The following chart summarizes our findings.



The square formed by the participants during our collaboration represents a biological system, by observing the choice of the chosen color for each word we are able to judge how an individual member would react in relation to the decision that the entire biological system finally made. As expected in the first words the participants heard the final decision was clear, the word fire brings to mind the color red, the word sky blue and the word forest green. The three words that showed 100% agreement between participants were the word fire, the word forest, and the words sky and dream. However, as we progress to much more complex concepts such as the word success or the word teamwork, the biological noise increases and now each participant can have a different opinion than what the biological system as a whole finally chooses. The most biological noise was presented in the words success and party on the island where the change of the decision of two participants would have a great influence on the final result.

The conclusions we draw from this action have a big impact on how we approach our system. It is also an explanation of the reason why the biosensor we designed consists of multiple populations. So, as our system aims to recognize and analyse multifaceted stimuli and combine information, the final decision must come from many populations and be the result of the majority of the decision of the individual populations. If we had designed a biosensor that consisted of only one population, it might be effective in detecting simple stimuli and recognizing small patterns, but it could not be reliable for making decisions based on complex stimuli, each of which has to have a different weight for the final decision. In conclusion, the proposed system consists of many subpopulations of bacteria and thus can overcome metabolic barriers and make better decisions since it is based on majority-based choices.

Finally, we would like to thank iGEM Patras because our collaboration took place during the Aegean Meeting they organised. Also, we would like to thank the teams that participated: Patras, Crete, Thessaloniki and Thessaly, Patras_Uni_Hellas for their excellent cooperation and the will to explore biological noise with us!

References

1. https://link.springer.com/article/10.1007/s11569-020-00366-4
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033672/

An educational process that arose during the first few months of our journey in the competition was the one with the team Thessaloniki. We reached out to them to organize a virtual game on Instagram based on a very popular board game. Every week one of the teams would post a mystery story related to synthetic biology, leaving the followers with a huge question. The members of this team accepted and answered questions from the public for 24 hours. After a day, the other team would reveal the end of the mystery story, finally answering the big question that had been posed to the audience.

Our collaboration aimed to increase public engagement with small questions about synthetic biology. Our followers had the opportunity to be concerned about "problems" that occurred in every iGEM team on a daily basis, as some of our mystery stories were indeed true. Troubleshooting is a big part of the iGEM competition, by creating those “SynBio Stories” we gave the participants a good picture of what paths our thinking should follow every day in the lab when problems arise or things don't go exactly as planned. We were happy to receive so many questions and possible solutions from synthetic biology fans. Some of them were very close to the real solution of the problems we were presenting each time.

One day in the lab we noticed that a plate was contaminated and maggots had grown on it. However, looking at them through the stereoscope, we noticed that they had grown into a beautiful shape that had a grace to it. Wanting to emphasize the spirit that mistakes are part of the process, and we can learn from them and become better, we decided to create a mini collage to emphasize that our mistakes, if they are harmless, can be very beautiful.

We also thought that we are probably not the only group that has encountered these kinds of problems, and that many of our colleagues may have made "beautiful mistakes". So we decided to approach them for a collaboration. We asked them to send us photos of lab errors that had an aesthetically pleasing look. We are so happy that the teams iGEM Tec CEM, Estonia_TUIT and iGEM-RUM responded. We saw beautiful mistakes in every picture they sent us, from gels that were not running in a proper way to single dots growing on plates. We thank them for not being ashamed to show the world that mistakes are pretty and useful sometimes, and we hope they enjoy the collage as much as we do!

iGEM MSP-Maastricht organised one more year the iGEM Proceedings Journal 2022, an online Journal accessible to everyone interested in synthetic biology. We are honored to be a part of it.

Through this initiative, we had the opportunity to review the field of biocomputing by exploring realted papers and finally submitting "A Review On Extraordinary Biocomputing Applications". Through this work, we provide an overview of the most eye-catching software and hardware applications of biocomputing, from tunable oscillators to biological encryption systems. Our goal was to help researchers and welcome newcomers to the field of biocomputing.

The procedure consisted of three main steps:

• 1. Submission Step: First, we had to write the review an submit it to the iGEM Maastricht organising committe in order to be peer reviewed.
• 2. Peer-Review Step: Then, we had to peer-review the papers of three different teams. At this step, our paper was also peer-reviewed by three teams.
• 3. Revisions Step: Finally, after receiving our reviews we had to integrate the revisions requested and submit our final improved paper.

This year's alteration lies in the fact that the three best articles, based on the pper-review grading, were forwarded to researchers and journal editors working in the field of synthetic biology for review and feedback. The articles and the review from Dr. George Church, Dr, Michael Funk and Dr. Yevgeniya Nusinovich are included in iGEM MSP-Maastricht team’s Journal 2022.

You can find more about iGEM MSP-Maastricht team’s Journal here and our final submission here

This year we had the pleasure of being in close contact with members of the Technion-Israel team. Our communication was multi-level and both groups were equally helped. In addition, it was especially pleasant to organize meetings where we could talk and see that we were not alone against the difficulties we faced.

Consultative approach

During our first communication, the dry lab members understood that when modeling their systems they would need to take similar approaches. So the idea to join our forces and knowledge and create a two-way consulting relationship began to become a reality.

Initially team Technion, who needed a kinetic based on enzyme equations sent a very early draft of their model to us so that we could understand the main key axes they intended to analyze. Based on knowledge we already had on enzymatic kinetics, we created a file with tips and scientific tools that could be useful to them during the development of their model. The proposals focus on areas such as:

On enzymatic kinetics we suggested using the COPASI software. COPASI is widely used in many research projects for: modeling biological, biochemical, and chemical systems, in the development of theory and computational methods,in the development of “wet” laboratory methods. This software allows the user to determine kinetic constants and production rates based on an experimental dataset. Also it gives the opportunity to predict how a system will evolve overtime based on kinetic constant the user has imported. Members of our team were already familiar with this kind of software and thought that is would be useful for team Technion to use it and reach us whether a problem came up.

We also suggested Matlab for running their kinetic ODEs. We provided them with useful tutorials on how to use Matlab and SimBiology.

On microorganisms growth we suggested using the Monod model. We provided them useful equations and diagrams in order to have a better understanding on the different faces of a growth curve. We also provided equations on Monod first and second order kinetics and we summarised a way to determine the kinetic constants based on experimental data.

Both teams were dealing with diffusion. On this subject, team Technion was already aware of the Fick’s Diffusion Law and intended to use it just like us. So we discussed on possible difficulties that would come up in the process of modeling diffusion and were open in new ideas and suggestions.

Finally, we suggested using the COMSOL software if team Technion was interested in dealing with matter transfer phenomena. This would maybe be useful if they wanted to simulate mass transfer in, outside a cell or across membranes.

On a follow-up meeting between the dry lab members of each team, we were so happy to hear that they actually implemented some of our suggestions.

Recording a podcast episode

As a result of our collaboration with the team Technion, the proposal to record a podcast episode came up. We were so happy to be part of the “Angel Roots” Podcast. In the episode our team guested we talked about the scientific part of the project as well as the financial part of the iGEM Competition. We were so lucky because team Technion had adjusted this episode’s questions according to our project and the bioinformatic aspects of it. We answered questions related to the following axes:

• Who are we and how did we found out about iGEM?
• Our project’s goal and its applications.
• What financial difficulties we faced during the fundraising process this year?
• Finally, we were asked to give some advice to the future iGEMers about the iGEM competition in general but also in groups that are thinking of revolving around bioinformatics. So in this case we also suggested some useful software tools that we used as well.

If you want to know more about the “Angel Roots” Podcast you can find all the episodes here and if you want to listen to our episode click here.

Mock Jamboree Judging Session

We were so happy that iGEM Technion-Israel invited us to be a part of the Mock Jamboree that they organised. The idea is that all teams participating will have the opportunity to make a presentation of their project in an “international” environment. This action is intended to occur after the wiki freeze and after the teams have prepared their final presentation for the Judging Session. It is expected to be a three-hour event with teams from different countries and projects that fall in different tracks of the competition.

Thus, a three-hour event will be organised where the teams will be invited to present their work similar to the way it will be done in the official jamboree. It will be a good opportunity to expose our project in an environment similar to that of the competition to see what questions the other teams will have. In addition, we will hear thoughts, comments and suggestions from the other groups on how we presented our results, but at the same time we will also be inspired by their work. We believe it will be a good opportunity to meet other participants with whom we have not worked so far, and we look forward to seeing their work and how they will respond to ours.

In June 2022 we took part in the exciting design collaboration by Queen’s University, McGill University, and Cornell University iGEM teams. Wanting to create an educational book to educate the public, these three teams invited us to send them a form filled with information about our favourite bacterial species. We chose the bacterium Bdellovibrio bacteriovorus, also known as The "Vampire Bacterium". Bdellovibrio is a genus of Gram-negative, obligate aerobic bacteria. One of the more notable characteristics of this genus is that members can prey upon other Gram-negative bacteria and feed on the biopolymers.* Our choice was based on our intention to show to the public that in nature there are several organisms with completely different ways of living, metabolizing and reproducing. As the young representatives of the scientific community, we believe it is important to make clear that every form of life is far more complicated naturally than it is in theory.

*Harini K, Ajila V, Hegde S. Bdellovibrio bacteriovorus : A future antimicrobial agent? J Indian Soc Periodontol. 2013 Nov;17(6):823-5. doi: 10.4103/0972-124X.124534. PMID: 24554900; PMCID: PMC3917220.

In June 2022, team iGEM Patras Med reached out to us and invited us to take part in a collaboration aiming to create a video called “iJET”. The collaboration was organized by two teams, Patras Med and Aachen. We were asked to film a short video explaining our project that was going to be a part of a bigger video that the two teams were about to create by combining all the videos they had received. We happily wrote a script and filmed the video in a park. Furthermore, we spoke about why we were taking part in the iGEM competitions and why we like it, in which track we were competing this year. Finally, we gave a brief explanation of the project, where we are aiming and what innovative solution we give to an existing project by using synthetic biology tools. Hope you enjoy the “iJET” video here.

We participated in a series of informative videos based on Biosafety Practices organized by Team IISER Mohali from India. This series aims to inform the public about the measures that are carried out in the laboratories and reduce the skepticism regarding Genetic Engineering and Synthetic Biology.

Our team demonstrated some of the Biosafety measures followed in our laboratory. It was a very fun and creative procedure! You can find our video here.

Through Pre Aegean (May 28th, 2022) and Aegean (July 10-12, 2022) meetings, we had the opportunity to meet the other iGEM teams, present our iGEM projects, earn about interesting things regarding sequencing and PCR techniques, get training in soft skills, and most importantly have fun!

We would like to thank iGEM Patras for the amazing opportunity to participate in this wonderful event and make memories and friends!

We are very happy for our contribution in creating an informative post for world dna day. Team Patras_Medicine invited you to take a photo holding one of the letters A, T, U, G. They then created a beautiful collage, creating a double helix structure, simulating the DNA. The post was accompanied by informative facts about the DNA. Best way to celebrate world DNA Day.

This year we faced many difficulties with the laboratory consumables and the equipment we had available to carry out our laboratory experiments. So when we needed two 96-well plates with black clear bottom, we turned to team iGEM Thessaly. The members of the team were very willing to send us what we needed and we thank them for their prompt and quick response. For our part, we were able to fill their need for two 96-well plates with black bottom that they were lacking.

We are very happy that through our cooperation we were able to cover the gaps of each group and help each other. We thank them for the excellent cooperation and communication in every step of the way. We believe that it is the competition’s spirit to form collaborations like this, when one team is lacking something and another that actually has a surplus helps.

We participated in the iGEM Crete initiative to create a collage on the occasion of the World Day for Safety and Health at Work. Each team participated with the photos of their members responsible for the safety and sent a sentence about why we consider laboratory safety important in our team. In this way, we brought the teams closer together and contributed to laboratory safety vigilance!