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Engineering Biology in Cambridge

 

The 2022 Cambridge iGEM team won a Gold Medal and received a nomination for the ‘Best New Basic Part’ special prize in the Undergrad Category at the 2022 iGEM Grand Jamboree. Their project ‘AdaptR’ worked on developing a synthetic biological integral controller for increased genetic circuit robustness.

iGEM stands for International Genetically Engineered Machine and is the world’s largest synthetic biology competition and community. The competition involves teams of undergraduates spending the summer within the lab tackling an important problem that can be solved with synthetic biology. The process is similar to founding and building a biotech start-up, including coming up with an idea, and implementing it in the lab. It requires working on many varied aspects of the project, including computational modelling, communicating with interested stakeholders, education, fundraising, and even presenting your findings at an international conference!

Cambridge has a long history with iGEM. Cambridge was the first UK team to compete, in 2005, and even won the iGEM Grand Prize in 2009, but had not entered a team since 2016. In 2022, led by the Cambridge University Synthetic Biology Society, the Cambridge iGEM team made a long-awaited return with our project, “AdaptR”. We won a Gold Medal, and received a nomination for the ‘Best New Basic Part’ special prize at the iGEM Grand Jamboree.

AdaptR was an entirely student-run team composed of 6 undergraduate students from diverse backgrounds and year groups: Sharon Ho (3rd year Medicine/Engineering), Anthony Phung (1st year Natural Sciences), Kazimir Uzwyshyn-Jones (4th year Biochemistry), Charlie Anderton (2nd year Natural Sciences), Shau’ri Wiggins (1st year Natural Sciences), Joni Wildman (4th year Physics), who were supervised and managed by PhD & MPhil Students, all members of the Cambridge University Synthetic Biology Society.


   What is AdaptR?

 

Synthetic biology is incredible and allows us to engineer biology with novel abilities and use it in many different applications. However, synthetic genetic circuits are fragile and often fail, especially when scaled to industry. AdaptR aims to fix this proverbial crack in the pillar of synthetic biology by improving robustness of synthetic genetic circuits. To achieve this, we apply engineering principles of control theory to synthetic biology to create an integral controller, which acts to hold the production of a protein at a reference level in response to perturbation, minimising steady state error.

AdaptR has numerous potential use cases, ranging from microbial drug delivery and biomanufacturing to metabolic engineering. To make our circuit as usable as possible, we made use of a one-step modular implementation to replace the gene of interest depending on the user. We also took a factorial approach to building our circuit, expedited by the use of a modular DNA assembly technique (JUMP Golden Gate Assembly). This was guided by extensive modelling, which allowed us to explore how varying the strengths of promoters and ribosome binding sites would affect our circuits and, thus, informed the most efficient path to building usable circuits.

To read more about our project, please visit: https://2022.igem.wiki/cambridge/index.html

Timeline of AdaptR

The journey of AdaptR started with brainstorming sessions during Lent Term held by the Cambridge University Synthetic Biology Society where people interested in the iGEM competition got together to share ideas. After team formation in April, we had more focused brainstorming and we had settled on our project by July. After we settled on our project, we worked on the various elements of our project, in both the wet lab and dry lab until late September. Simultaneously, we also worked on other important aspects of any iGEM project, such as ‘Human Practices’ (engaging with stakeholders to show that our project is responsible and good for the world) and Education and Outreach. Everyone had different roles and worked together in order to carry out experiments and obtain results. To ensure our work would remain available as a resource to future iGEM teams, as well as the wider synthetic biology community, we also needed to document our work on our Wiki, gaining useful web design skills in the process.

Nomination for Best new basic part

Since its inauguration in 2003, iGEM’s ethos has always been to develop and curate an open-source Parts collection (called the iGEM Registry) for biological research. Every year, as part of their projects, each team will design, build and characterise many new Parts and improve on existing Parts. They will then submit the sequences and carefully document the design rationale and characterisation results on the Registry, which are then made available to everyone.

This year, our team designed and constructed a multitude of components that could be assembled into a more complex circuit. One of our submissions was well-received by the judges, earning its spot among the Top 5 Best New Basic Parts in the whole competition. This prestigious nomination is dedicated to the newly-improved araBAD Promoter (or pBAD for short). pBAD is a regulatory region of the native araBAD operon in E. coli, responsible for arabinose metabolism. Though it is widely exploited in genetic circuitry and fundamental research, the promoter is quite long and has sub-optimal strength. One of the team members, Anthony, set out to reengineer an improved version (called pBAD_AP) which is not only half the original length but also displays a fourfold increase in maximal activity. The Part is now accessible on the Registry, and we hope it will become useful for future teams and research applications.

To read more about this Part, please visit the Registry at: http://parts.igem.org/Part:BBa_K4491007.

The Jamboree

In iGEM 2022, the Grand Jamboree was held in Paris for the first time. The Grand Jamboree features booths and presentations from international iGEM teams, startups and other biotech companies. It was a fantastic experience for us all to meet, engage with, and learn from both experts and other iGEMers from all over the world. It also gave us the opportunity to present our work in front of an international audience of synthetic biologists.

Why should you join iGEM?

iGEM is a uniquely rewarding experience and a fantastic opportunity to learn - hear what the AdaptR team members have to say below:

“iGEM gives me an opportunity to brainstorm, design and execute a project from scratch in an area that I am passionate about and learn how to work together as a team. This experience gives me a chance to both improve on my wet lab skills and modelling skills. iGEM is not only about science where I also get the opportunity to make YouTube Videos to educate the public about the topic I am interested in. Most importantly, it feels amazing to be around like-minded people with a similar passion, I am very thankful for the friendship that I made during iGEM.’’ - Sharon Ho

“iGEM was a fantastic experience, it really allows you to drive your own project through from start to finish, so you end up really invested in the project. It was great fun, and it gave me fantastic experience in the lab, which has already been extremely valuable in my final year project, and I’m sure the head start it has given me will continue to be valuable as I start my career. Working with such a fantastic group of people, team members and instructors really made the experience for me, and I learnt so much from everyone over the summer.” - Charlie Anderton

“iGEM is comparable to building a start-up and the single most valuable summer experience I have had. It teaches you about the world of synthetic biology and has developed my wet and dry lab techniques as well as interpersonal skills. Notwithstanding that the competition was extremely fun as you meet other competitors from around the world. I am incredibly grateful for the opportunity iGEM gave me.” - Kazimir Uzwyshyn-Jones

“iGEM came to me as an excellent opportunity to both develop my passion in synthetic biology and meet new formidable rivals through competitive sportsmanship. I have also gained invaluable experiences, from operating complex instruments, computational literacy, to science communication and entrepreneurship. Cambridge will be running the competition again after this year’s success, and I hope more people will take on the challenge!” - Anthony Phung

“iGEM has given me so many experiences, and taught me so many lessons that I have been able to take forward and use beyond the summer. Not only has it given me the opportunity to learn invaluable wet-lab and dry-lab skills but I was also able to build my independence in the lab by handling one of our side-projects, through which I was able to build on my computational data analysis skills too. On top of this, I was able to revisit an old interest in 3D printing and CAD in order to meet one of our medal criteria which was a great opportunity. For me, it was the best use of my summer, and it really packed in a lot of experience that is invaluable for a future in the scientific field.” - Shau’ri Wiggins

Sponsors

Finally, we would like to thank all of our Sponsors, particularly The school of Biological Sciences, Evonetix, bit.bio, Integrated DNA Technologies, Twist Biosciences, Colorifix and C2D3 Computational Biology for supporting Cambridge iGEM 2022. A big thank you also to Biomakespace for letting us use their lab space, as well as to our Departments, Colleges (Gonville & Caius College, St Catharine’s College, Queens’ College, Peterhouse College and Murray Edwards College) and everyone who contributed to our success.

Getting involved

To know more about iGEM at Cambridge or to get involved with future Cambridge iGEM teams, please get in touch with the Cambridge University Synthetic Biology Society, who will be hosting information, brainstorming and team-selection sessions during Lent Term 2023. To connect with us and to view the current assignment set for those interested in joining the 2023 Cambridge iGEM team, please visit: https://linktr.ee/cusynbiosoc

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