Synthetic Biology, Parkinson’s Disease, iGEM and Us

Matt Rogan & Karen Fung
Edited by Will Stanley

iGEM

iGEM stands for the “International Genetically Engineered Machine” competition. First starting at Massachusetts Institute of Technology (MIT), the competition comprises of teams of either undergraduate, postgraduate or high school students from over 45 countries who represent their institution by coming up with a project that aims at solving world problems using synthetic biology. During the summer project, each individual team has to fulfill a number of achievements to be awarded a medal (bronze, silver or gold) at the Giant Jamboree held in Boston Massachusetts, USA every year, which up to 6,000 fellow iGEM-ers attend. Teams that have made special contributions can be awarded special prizes (we were nominated for a measurement prize) and the most phenomenal project wins the grand prize… the Biobrick Trophy. There is a lot to talk about with iGEM, so I will try and break down what synthetic biology is, the work we had to do and the importance of what a competition like iGEM means.

At the iGEM Giant Jamboree 2019.
The iGEM grand prize! The Biobrick trophy.

What is synthetic biology?

I’ll explain synthetic biology to you the way it was explained to me! Picture a house and break down all of the parts that make it up: you have the bricks, cement to hold the bricks together, windows, doors and roof tiles. We can take these individual parts to build the house and copy it take make an exact replica with the same rooms and dimensions. Alternatively, we can build a completely different one with more rooms and floors. The outcome may be different, but the parts we use are the same.

Building a house as an analogy for synthetic biology.

In synthetic biology, we use the same analogy by breaking apart a cell into its most basic parts, starting with DNA, the famous genetic template for building life. For one gene on a strip of DNA, you have the:

  1. Promoter – the part that tells the cell where the gene is and where DNA is copied into a sequence called messenger RNA (mRNA). mRNA transcription of a gene starts.
  2. Ribosome binding site (CDS) – where the transcribed gene or RNA binds to the ribosome- the ribosome is where a protein is produced
  3. Coding sequence (CDS) – the coding region of a gene, the bit that codes for a protein e.g. the gene that encodes for insulin
  4. Terminator – the part that tells the cell machinery where the gene ends
Designing and sythesising a functioning gene from basic parts.

We call these four things “basic parts” and adding them together makes a fully functional gene, AKA a “composite part”, which codes for a protein. Like the house, we can build a gene made up of these basic parts. The good thing about this is there are many versions of each part, so can build unique genes. For example, by having a promoter that produces lots of mRNA, you can increase production of a really useful protein such as insulin for managing type I diabetes. Alternatively, you can recode a whole organism like the synthetic Yeast 2.0 project. Using this method of standardization is extremely advantageous in terms of accessibility and manipulation in biology, with many now adopting this approach.

A designed synthetic gene built from DNA makes mRNA, which goes to a ribosome to make a protein (such as insulin). That protein is then ready to do something useful, by design.

Our iGEM project

We had a team of students from a number of disciplines such as molecular biology, computer science and chemistry; for Newcastle’s 2019 project, we wanted to address the problem with the diagnosis of Parkinson’s disease, which is made based on motor symptoms like a tremor or shakiness. The problem with this is that by this time, the part of the brain that is affected by the disease, the Substantia nigra, up to 60% of neurons in this area are damaged or destroyed. This part of the brain is responsible for motor functions such as movement, so damage to this area leads to the symptoms of Parkinson’s disease. Despite this, symptoms not associated with motor problems can occur earlier, which indicates early onset of Parkinson’s (tiredness, fatigue and disrupted sleeping). We wanted to address this problem through developing a multi-diagnostic tool that can detect early signs of Parkinson’s disease using blood or skin samples. Using synthetic biology, we aimed to develop three biosensors that could detect three biomarkers. A biomarker is a naturally occurring molecule or gene that is associated with a disease and a biosensor detects these biomarkers. We designed our biosensors to detect the levels of each biomarker and how these levels differ from a healthy individual as the levels of these biomarkers change when someone is suffering from Parkinson’s.  We made three biosensors to detect the following molecules associated with the disease: a glutathione biosensor, CPLX1 biosensor using CRISPR Cas13a and an eicosane biosensor. The latter unfortunately didn’t work as we’d hoped, but the other two were successful!

Newcastle University 2019 iGEM team.

There were a number of things that we had to do for this project, including wet-lab work computational modelling, web design and human practices. The wet lab work was expected and most of us already had some experience – but the great thing about iGEM is the push to work outside of your comfort zone and learn skills in an area that is so important for the development of your project, such as kinetic modelling of our CRISPR system which helped inform and improve our project design. Not only is modelling our system important for predicting it, it also helped us secure a gold medal!

iGEM also gave many of us the opportunity to meet people whose lives could be impacted by the research in this area. With human practices, we engaged with members of the public directly affected by Parkinson’s disease (carers and those living with the disease), as well as doctors and researchers in the area of Parkinson’s diagnostics whose insight further informed and improved our project. Human practices really put into perspective how important the work researchers do; seeing the dedication of their research, along with meeting those whose lives can be massively impacted in a positive way by this research is very moving and shows the importance of their work.

For more information about Parkinson’s disease, please visit the Parkinson’s UK website.

Reflections on the iGEM experience

Now we can honestly say iGEM is an experience like no other. As  undergraduate students, you do not really have too much opportunity to partake in a group project where the students get to come up with the project, especially one where you can spend months in the lab working alongside experts in the field who help your idea come to fruition. We developed so much knowledge and so many skills in synthetic biology, and how to carry out a meaningful project over that summer. iGEM provided an opportunity to have fun with science and think outside the box. One of the most important things we learnt from this experience was that any result, even if it was deemed “negative”, was still valid. As scientists, it is tempting to disregard unexpected results but iGEM taught us that any result is still a result and it allowed us to build upon discoveries to achieve our end goal. Being in a multidisciplinary group, it allowed us to gain experiences outside our field – for example, website coding was new to some of us and something we can take away from our iGEM project.

Really in this time, we probably learnt more from this experience than in our whole degrees. But, the most rewarding thing about iGEM was the sheer sense of community when it came to the Giant Jamboree in Boston. It’s not often that you can be in a room of 6,000 people, coming together from all around the world – all of whom have gone through the same summer experience as you – to applaud everyone’s hard work, achievements and most of all celebrate our collective passion for science. When you do, it is euphoric. Our team sadly didn’t win the grand prize for Newcastle this time but we won a gold medal and a measurement nomination, which was great to show that our hard work paid off. We cannot put into words what an amazing feeling that is.     Overall, it’s an experience like no other. We learned a lot, met some incredible people, made friends for life and had many sleepless nights during the final week of submission. Projects and competitions like iGEM give students a real experience of what science is all about.   If you want to look at our project, then feel free to check it out here.

About the authors:

Following their iGEM project, Matt Rogan is now studying for a MRes in Biotechnology and Biodesign at Newcastle University.  He’s currently applying for PhD positions, with the ambition of a future in synthetic biology.

Karen Fung is close to completing her 4-year MSc in Cellular and Molecular Biology at Newcastle University and is looking for a PhD position. Her interests are in microbiology and synthetic biology.

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