Team:Manchester/Description
Project Description
Main Achievements
- We proposed a novel environmentally friendly sunscreen from hippopotamus sweat that could overcome the coral bleaching issues associated with traditional sunscreens.
- We used computational retrosynthesis to identify a plausible biosynthetic route to this compound.
- We designed expression vectors for the implementation of this novel biosynthetic pathway in E. coli.
- We used constraint-based modelling (flux balance analysis) to explore the function of our new pathway in the context of chassis metabolism.
- We used a variety of techniques from the social sciences to reflect, challenge and inform our project planning:
- Interviews with stakeholders, including dermatologists, sunscreen producers and potential customers.
- An innovative analysis of sunscreen media on YouTube, YouTube Analysis.
- Survey analysis to assess internal biases towards synthetic biology.
- Survey analysis of sunscreen use habits and attitudes.
- Reflection on how our project interacts with the sustainable development goals.
- We prepared a comprehensive Business Plan to identify a route towards commercialising our innovative product.
- We conducted extensive Market Research to determine the essential characteristics our product would need to have to succeed commercially.
- We contributed to the wider iGEM community by:
- Building an Essential Entrepreneurship Learning Resource.
- Performing a statistical Wiki Study analysing what makes a successful iGEM Wiki.
This year the Manchester team project is to design and integrate our own pathway for the production of Hipposudoric Acid in E. coli bacteria. Hipposudoric Acid will act as a novel UV filter to reduce the oxidative stress experienced by corals minimising bleaching events.
When we began our iGEM project we were adamant as a team that we wanted to do a project around skin cancer. In 2017 skin cancer was the 5th most common type of cancer in the UK yet in 86% of cases it is preventable. The prevalence of melanoma skin cancer is also becoming more frequent as incidence rates have increased by almost 38%, in females rates have increased by 30% and in males 47% (1). This is an extremely worrying statistic. To begin our literature research we started looking into different challenges around skin cancer including sunscreens. It was at this point that we discovered the paper “Sunscreens Cause Coral Bleaching by Promoting Viral Infections” by Danovaro et al. We were shocked to learn that conventional sunscreens contribute to coral bleaching by inducing the lytic cycle in viruses (2). Coral reefs are a beautiful and important ecosystem and although they cover less than 1% of our oceans, they are home ¼ of all marine life (3). It seemed logical that our iGEM project should attempt to rectify both problems by designing a new form of sunscreen that would alleviate the stress corals experience.
Around 5pm on New Year's Eve, a member of our team was settling down for an evening of watching David Attenborough's Natural World. This particular episode happened to focus on hippopotami and their magical sunscreen sweat. We were consumed by the striking story of these huge naked animals battling the sun head on. Quickly, realising this could be the answer we were looking for we began researching. It was then, at the beginning of the new year that we identified Hipposudoric Acid. It was said that this compound turns the Hippopotamus sweat a rich red colour giving the animal the ghostly appearance. After literature research into these mysterious compounds we found a paper by Saikawa et al. reporting the acid's identification and initial characterisation, but we could find no paper describing the biosynthetic pathway of this acid in the host organism or any other system (4). This began our exciting iGEM journey.
How have we conducted our project?
The microbial production of Hipposudoric Acid provides a promising bio sustainable manufacturing solution to reduce the oxidative stress experienced by corals when people use sunscreen.
The Design platform for our project encountered an initial problem because we had no prior information on the biosynthetic pathway for Hipposudoric Acid. We had to resort to computational retrosynthesis to address this challenge, a strategy that has rarely been used in iGEM before. For the retrosynthesis, we used Retropath2.0, a software that can be used to identify biochemically plausible pathways leading to the target compound starting from the host metabolism (6). Being the first iGEM team to use Retropath2.0 was ambitious and caused plenty of challenges; we had to go through a rigorous troubleshooting process. For example, the final step in the synthesis of Hipposudoric Acid is probably not an enzyme-catalysed reaction, and may not be detected by a Retropath search. At this point, we found a paper hypothesising the microbial production of an ochronotic pigment in E. coli, which proposed the potential oxidative polymerisation of homogentisic acid (HGA) (5). Therefore, we decided to run Retropath2.0 using HGA as our target compound and then applied basic organic chemistry mechanisms to HGA to suggest a plausible non-enzymatic route to Hipposudoric Acid. Having overcome this initial hurdle our project continued as follows:
- Enzyme Selection - Selenzyme.
- DNA parts design.
- Experimental design.
- BUILD - cloning and part preparation.
- TEST - protocols to characterise Hipposudoric Acid and mass spectrometry of HGA.
Due to limited laboratory access caused by the COVID-19 pandemic we have had to be creative this year with how we were going to visualise and develop our project without wet lab elements. To do this we have greatly expanded our human practices work to better understand how our HippoSol product would interact with key stakeholders. This has allowed our team to remain reflective throughout the dry lab stages of our project, ensuring we produce something next year that is responsible and good for the world. Another way we have done this is by exploring entrepreneurship to begin to understand our project as a commercial product, not just as a scientific endeavour. We have produced a full business plan for our project HippoSol including characterisation of potential consumers and segmentation of the sunscreen market. This has forced our team to view our project under an entrepreneurial lens, which taught us to begin prioritising consumer values in our Human Practices. Below is a list of the different aspects of our project that informed our experimental planning:
- Interviews with stakeholders;
- Analysis of sunscreen media on YouTube;
- Survey analysis of internal biases for synthetic biology;
- Survey analysis of sunscreen habits;
- Business Plan and Business Report;
- Essential Entrepreneurship Learning Resource;
- Dual Use and Safety Considerations;
- Planning of future wet lab protocols;
- Wiki Study analysing what makes a successful wiki;
- Flux Balance Analysis;
- Implementation of our project - including how our project interacts with the sustainable development goals;
- Reflection on our Human Practices and steps taken to ensure our project is responsible.
