Team:UCL/HP/Gold

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UCL iGEM 2016 | BioSynthAge

HUMAN PRACTICES: GOLD




OVERVIEW

Our project has evolved from a single idea to a multidimensional project that extends the healthy lifespan through many routes. The influence of human practices has formed an integral part of our project and has greatly changed not only the design of our therapies, but the team’s perception and understanding of the problem. We truly believe that every person we have interacted with within our human practices has resulted in either changing the way the team thinks about our project, to an addition of a new BioBrick or an improvement to the design of our ideas.


See our integrated practices page for a detailed overview of how human practices has shaped our whole project. See below for how each topic explored has changed the design and execution of some of our sub-project ideas.



Understanding ageing: From the beginning


Our experience at the Dementia care home really gave us an insight to the life of an elderly person with an age related disease, we loved listening to the stories of the elderly over a cup of tea! Not only could we understand first-hand how Dementia has impacted their lives, but we could ask our potential end users directly if they would go as far as synthetic biology to prevent them from getting Dementia and other age-related diseases.


Our interaction with the elderly pushed us to go further and actually personally find out how it is to be old, which is why we designed and tested our very own old people simulation suit. The team members felt that it was a painful, yet eye opening experience and again, really made us realise how ageing can make doing everyday tasks a lot harder to carry out. It was a miniature expense in terms of time and money, but valuable in investment and what we learnt.


At this point, we knew that we wanted to do an ageing project, but we were still deciding which aspect to focus on. The ageing simulation suit and our interactions with the elderly made us realise that ageing is something that causes a lot of problems which make everyday living harder. We wanted to improve the quality of life and by doing so we realised that our therapies should be targeted towards most vital parts of the human body to make the biggest impact to the quality of the ageing populations lives. As a result, we started to research vital organs such as the heart and lungs which really can cause a lot of problems as we age.


The experts: Formed an integral part of our biobrick designs


Our interactions with the experts formed a major part of our project. Our current understanding of ageing was basic, and in order to build therapies that were going to work, we needed to find out what people who dedicate their careers to the field think. Initially, we spoke to our main project inspiration, Aubrey de Grey (the full skype video can be seen here). Aubrey mentioned that our lycopene idea was promising if the data we obtained showed that Lycopene can survive in the gut, can successfully secreted from the bacteria and if our genetically modified bacteria can survive under low pH of the digestive tract. Filipe also agreed that that we need to think about how to create a compelling proof of concept for our cassettes and to get enough evidence from the experiments that show that the Lycopene secretion will not be effected by the gut and that Lycopene will not affect the gut microbiota. As a result of talking to Aubrey and Filipe we designed further characterisation tests for our lycopene biobrick. More specifically, we now aim to stress our bacterial cells to then see the effect on the growth of our bacteria as well as the secretion of lycopene compared to wild type cells.

We also collaborated with Dundee GEM team by sending our lycopene construct to them, so they can simulate if our bacteria survive under stomach conditions using a stomach simulating device.

From talking to Filipe, we realised that developing a probiotic is much more complicated than we initially thought. Which lead to us enquiring – what if we have a multi-solution approach where we focus on many organs to increase impact on healthy lifespan? Filipe and Aubrey inspired us to think of new and more effective ways that we can increase healthy lifespan that may be more effective if combined with our lycopene probiotic. Hence, the birth of a new idea: SOD3 gene therapy.



Maximina, an expert in senescent cells had really helped us understand that the research in senescence and ageing is new and there is still a lot of confusion about the markers of senescent cells and whether these cells are good or bad for us. Which is why, the UCL iGEM team came to the conclusion of dropping our senescence and ageing idea, because we felt that the safety risks were too high.


Our interaction with William Bains was extremely useful. We came to the conclusion that it might be better to combine many antioxidants and overexpress more than one in one biobrick. He also suggested that an oxidative stress sensitive promotor that only responds to high levels of oxidative stress might be a good idea to put in front of our SOD3 and lycopene construct. And that we can titrate the system (add more binding sites) to only express the gene when high levels of oxidative stress are detected. As a result of this interaction, we decided to add the nfkb promotor to our SOD3 biobrick to increase safety of our device.


As a result of talking to the experts, we realised that we could have a better impact on increasing healthy lifespan if we had a multidimensional approach with more than one solution. We introduced our Superoxide dismutase 3 BioBrick to our experimental plan. When we fed this back to other experts such as Piers and Alexanda Stolzing they approved and also thought that it was a good idea. Talking to Maxwell from Sigma Biosciences has enabled us to think more about the route of delivery of our lycopene system. He mentioned that a faecal transplant may be an easier way to put bacteria into the gut compared to a probiotic.


Outreach: More than just educating the younger generation


We started outreach with the aim of educating the younger generation about synthetic biology and the importance of healthy ageing. We understood that a lot of the general public do not see ageing as a disease, or yet even as a problem so we wanted to educate them through our interactive workshops. However, we did not expect that we would learn so much from these outreach sessions and that it would shape the execution of our project as much as it did.


We came to realise that ageing will effect nearly everything, from the economy of the world to overcrowding issues. It has a lot of positives as well as negative implications as we have learnt not to ignore but to embrace these. Hence why our outreach has been integral to the execution of our project.


The debating sessions really helped us visualise that ageing research is not just a great thing for society but also raises a large about of issues that are long term. Some of the students raised issues that the we didn't even think about. For example, year 12 students mentioned that overcrowding and a change in the pension scheme will result from people living healthier lives for longer, which may be a negative implication of ageing research. We noticed that the more debates we organised with different classes, more points were raised which increased our perspective on the implications of our project.


We really understand that as ageing is a global problem, we want to incorporate as many perspectives, issues, barriers towards our project as we can in order to fully evaluate the benefits to our therapies. Outreach inspired us to then reach out to as many different people as we could to broaden our network to the wider community and making our project integrated into today’s society.

Public engagement and education


Through talking and interacting with the public, we were able to not only educate them about synthetic biology innovations, but to also learn about what our end users are afraid of with our therapies. Once we listened, and engaged in a 2-way conversation, we then understood that our project can impact nearly everything. From pension schemes to the socio-economic demographic, and that we needed to consider these factors through our project.


With that being said, we also learned that most all of these challenges and long term implications can be worked through with enough consideration, making us comfortable with the notion that our ageing therapies could do a lot of good if it were implemented in the real world.


Public engagement has really developed our ability to communicate our project and ideas to a wide range of audiences and execute our project. We now understand that good communication is important as these therapies will affect them and their lives.