A novel potential treatment for people with spinal cord injuries developed by KCL undergraduates won “Best Therapeutics Project” in a competition run by the International Genetically Engineered Machine (iGEM) Foundation, aiming to improve daily problems by pushing the boundaries of Synthetic Biology.

Renervate, a team of 19 undergraduates in KCL’s faculties of Bioengineering, and Life Sciences & Medicine, even competed in the “overgraduate” category. Throughout 2020, the team worked in unprecedented circumstances to develop the award-winning concept. Now looking forward to the next phase, they are recruiting through a new society for Biotechnology & Synthetic Biology, accepting applications from all disciplines.

Globally, up to half a million people live with a spinal cord injury (SCI), which causes loss of motor or sensory function below the site of injury. Every year in the UK, around 3,000 people are diagnosed with SCI. The spinal cord hosts nerve cells (neurons) and their long fibres (axons) transmitting motor and sensory information between the brain and body. Renervate’s short explanatory video likened the spine to a highway, and spinal injury to a “long, lasting pothole in the road, that neurons are unable to cross”. Currently there are no treatments to restore function in the severed spinal nerves.

The project’s title: “Creation of a 3D-bioprinted polycaprolactone scaffold with mussel-foot protein Pvfp-5β-based bioadhesive coating for biomedical applications.” To pick this apart in colloquial terms and to hear more about the process, Roar interviewed co-leaders of the Renervate team, Abigail Conner, a Molecular Genetics finalist, and Steph Avraamides, Biomedical Sciences finalist, as well as Harsh Bumia, Biochemistry finalist, and Head of Structural Modelling and part of the sub-group that focused on the mussel-foot protein itself.

Abigail and Steph, both at last year’s iGEM competition, encountered a burn treatment derived from the protein of a squid. “We thought that was so cool because it was such a unique way of approaching a problem that affects so many people”. This was spurred further by encountering a paper by Professor Annalisa Pastore and Dr Caterina Alfano on a mussel-foot protein as a potential bioadhesive. This protein itself is genetically engineered in labs at King’s, where well-researched bacteria (E. coli) produce the same protein that the mussel would naturally produce.

Image credit: KCL ‘Renervate’ iGEM page. The innovative treatment aims restore function to severed nerves.

The mussel foot protein should allow regrowth of the neurons at the site of injury, Abigail said. “Attachment and adhesion are super important for any sort of tissue engineering situation, especially for the spinal cord… This bioadhesive coating could be used in all sorts of tissue engineering applications like tendon or ligament repair, because it focuses on that really important element of adhesion.”

The scaffold is made of polycaprolactone because its mechanical properties match those of the spine, allowing nerve cells’ axons to reconnect with the spinal cord to heal naturally and eventually to restore fully. Harsh outlined that “the thing is, although it’s biocompatible and biodegradable, which is great, it is not very adhesive, so if you put it into the [area of injury] it wouldn’t really stick per se, for lack of a better word, so we’re using our non-cytotoxic [i.e. not toxic to cells] muscle foot protein to coat it which will enable the cells to adhere to the surface of the scaffold.”

As the first Covid lockdown struck, iGEM adapted the competition to allow the first phase to be modelling and design aspects. Abigail said, “We had to really think about ‘what are some ways in which we can explore our project without being able to do anything in the lab?’… It was a challenge because you weren’t there in person to be like ‘ok let’s just go out and have a talk’.”

Once May exams were over, the project went ‘full throttle’. Scattered across the globe amidst a global pandemic, the team united for a common goal, collaborating on Slack and Zoom, and hosting socials, from Among Us to painting. Whilst pleased everyone was safe at home (in the USA, Australia, and China), Steph said that with team members scattered across the world “Abbie and I had quite a mountain to climb. It was a logistically interesting time to work out how we could overcome this… Whilst last year we were in laboratory with our Principle Investigator everyday, this year we benefited from their virtual support and guidance, but also from the skills we gained from the independence and responsibility entrusted to us.”

In iGEM and more generally, Steph said, “the importance of sharing ideas, collaboration, and co-operation in science can’t be overstated.” Harsh added that “if you think about it, any major scientific discovery, Nobel prize winners, they haven’t come to these conclusions on their own, they’ve built upon at least several years of research, so it’s a team effort… it’s about collaboration as much as competition. At the end of the day, we’re there to further science and help the world in some sort of way.”

The project had an important non-scientific side. “Designing one therapeutic treatment without regards to holistic approaches won’t be the most optimal way forward” Steph said. Meeting with the Spinal Injuries Association over the summer “was an honour and really did shape our understanding of spinal cord injury and inspire the direction of our project”. The discussion included “the importance of language, how the public use words [and] the role of the media in portraying the injury”.

Abigail pointed out that “individuals with spinal cord injury aren’t disabled, it’s society that disables them. So it’s about being able to take away these challenges that exist in society to make the world better for them first. These bigger societal barriers need to be taken down in conjunction with the science.”

Renervate clearly moves humanity closer to a restorative treatment for people with spinal cord injury. The team is optimistic about applicability in the real world, even in veterinary contexts. Future plans include hospitals with sterile, automated 3D bioprinting rooms, but Steph said, “it’s definitely a long road ahead if it is successful”. Whilst looking beyond iGEM, in the short term the team look forward to returning to labs for the next phase in January. Whilst at King’s they are hoping to foster a community focusing on Synthetic Biology, with Harsh believing that it has “great uses in a range of projects”.

The Renervate project is self-funded and to help support its progress, it continues to accept any public donations on its GoFundMe page, available at https://www.gofundme.com/f/kcl-igem-2021

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