Students compete in international synthetic biology tournament with a model to assess risks of Antarctic bacteria

Identifying the risk of new mechanisms of resistance to antibiotics in bacteria discovered in Antarctica and formulating molecules that allow these properties to be inhibited are part of the objectives of Tan Tari Bricks, a team from the University of Chile and the only one that represents the country in iGEM Design League 2022, one of the largest synthetic biology student competitions in the world. During the end of October and the beginning of November, the team must present different advances of its work, which proposes an experimental model and computational biology, as well as educational actions and incidence in public policies.

Communications University of Chile.- Last March, the scientific magazine Science of The Total Environment released a study on the discovery of numerous bacteria in Antarctica with hyper-resistance capacities against different antibiotics and other antimicrobial substances. The article presented part of the results of an extensive investigation that during the years 2017 and 2019 collected soil samples from different points of the Antarctic Peninsula. The work, headed by the academic of the Faculty of Sciences of the University of Chile, Andres Marcoletaalso warned about the risk that this phenomenon posed for public health, especially in the context of climate change and the increasing movement to and from the White Continent. He also raised the possibility that the hyperresistance properties found in Antarctic bacteria could be transferred to pathogens.

The discovery, as amazing as it is worrying, raised a series of new questions, some of which were addressed by a group of students from the University of Chile. This is the origin of Tan Tari Bricksa team that has been working since June on a proposal that integrates an experimental model and bioinformatics to understand and evaluate the resistance properties of these bacteria, generate possible inhibitors of these mechanisms and check whether these resistance capacities can be transferred to other pathogens. The initiative was presented to the iGEM Design League 2022, the Latin American section of the largest synthetic biology student competition in the world, a tournament where this group is also the only Chilean representative.

The project is limited to the search for answers and solutions to the challenge of antimicrobial resistance. The phenomenon is considered a threat to global health that could mean about 10 million deaths per year by 2050, which is why health authorities have emphasized the need for an interdisciplinary approach to establish policies and actions aimed at investigating its causes, monitoring its occurrence, and mitigating its impacts on different ecosystems. In this line, Tan Tari Bricks not only proposes a scientific model to know and counteract the resistance properties of these Antarctic bacteria, it also proposes actions to educate the population and influence public policies that allow facing risk scenarios for public health.

Science, education and public policy

Based on some resistance genes found in Antarctica, the team proposes a “design based on synthetic biology and computational biology, which makes it possible to take these genes, put them inside a model pathogenic bacterium, and study whether these genes really confer resistance to the bacteria. In addition, it will seek to predict which antibiotics in particular the new resistance genes act against and a search will be made for possible molecules that inhibit these resistance mechanisms among thousands of known natural compounds. This proof of concept, based on the knowledge of these Antarctic resistance genes, would allow progress in dealing with possible pathogenic bacteria that may arise in the future”, explains Andrés Marcoleta, who integrates the project together with the teachers Juliet Orlando Y Francisco Chavez as instructors.

In its scientific line, the The study proposal is focused on the so-called beta-lactamases, a variety of enzymes capable of inactivating and degrading beta-lactam antibiotics, such as penicillins, which are currently the most widely used to treat infections globally. “To assess their potential risk, we propose the use of computational biology to predict which antibiotics these new beta-lactamases would give resistance to (spectrum of action), as well as whether or not they would be sensitive to currently available inhibitors to neutralize these mechanisms. of resistance. Likewise, the project contemplates an experimental strategy to test the resistance properties of the new beta-lactamases in a model pathogenic bacterium”, details the team.

On the other hand, the design plans to develop new inhibitors directed especially against these Antarctic beta-lactamases. “Furthermore, we propose a method for large-scale testing of rationally designed variants of these inhibitors, in order to obtain optimized inhibitors. This will allow the discovery of new Antarctic resistance genes to antibiotics and the development of new inhibitors for these new mechanisms before their possible appearance in pathogenic bacteria”, state the members of this initiative.

Learn by researching

During the end of October and the beginning of November, the team must present different advances of their work before the competition jury. The award ceremony will be held on November 26, where the winners of the iGEM Design League 2022 will be announced., who will receive funding to implement different stages of the proposed design. The first place will also win the opportunity to participate in the iGEM Grand Jamboree, a global meeting that will bring together the winners of this competition from each region in Boston, an instance where mentoring and meetings with companies and entrepreneurs in biotechnology from all over the world are held. world.

Regarding this regional competition focused on the development of solutions to local and global problems through synthetic biology, Professor Francisco Chávez points out that “it is the first time that Chile participates in this new initiative, although several Chilean teams have participated in the Grand Jamboree, the most important Synthetic Biology competition in the world and that the iGEM Foundation organizes every year with teams from all continents”. In fact, he comments that two teams from the Faculty of Sciences of the U. de Chile participated in the 2017 and 2018 editions of this competition held in Boston, obtaining a Bronze medal in the last edition for their marine toxin biosensor prototype designed using synthetic biology. In this sense, he comments that “the participation of Chilean teams in these instances has been fundamental for the promotion of innovation and particularly in the use of synthetic biology in new ventures and biotechnological solutions”.

Who leads this team? Amelia Cox, student of Molecular Biotechnology Engineering at the University of Chile, who coordinated the team to fulfill each task. Regarding this experience, he highlights that it has been challenging and “extremely enriching professionally and personally, since it has meant learning from an area that is not my expertise, such as resistance to beta-lactam antibiotics and the development of inhibitory proteins. . In addition, I have been able to develop and improve skills around the different deliverables of the competition, such as writing a large amount of writing in English, creating audiovisual material and collaborating with teams from other countries. But above all, I think the coordinating such a complex team, such as one made up of undergraduate and graduate students and professors, has been the greatest challenge, but at the same time a task where I have had several learning and where I confirm the idea that teams should be understood as human groups where working towards a pleasant and collaborative environment is key”.