Team:Oxford/InitialIdeas
Initial Ideas
Prior to our initial survey, we had many different ideas for potential projects:
| Idea | Track | Benefits | Limitations |
|---|---|---|---|
| Biodegradation - Removal of nitrates from water systems to reduce effects of eutrophication | Environment | High demand for environmental projects Potential to use framework for broad water purification applications | Biological containment issues Availability of chassis may limit scope of experimental data |
| Snake Bites - Using protease composition to distinguish between different venoms | Diagnostics | Large impact in developing countries High accuracy of protease detection | Hard to improve upon previous projects Difficult to create cell-free device |
| Latex Allergy - Designing a filter with an agent to bind/degrade the putative latex allergen hevein | Therapeutics | No current treatments focus on preventing latex exposure due to allergen molecule size Possible application for other airborne allergens | Very small population affected Lack of existing research: unclear if allergen cleavage reduces the response |
| Date Rape Drug Sensor - Designing a cell-free biosensor for the detection of benzodiazepines in drinks | Environment | Important real world issue Potential to build upon successful previous projects e.g. E.Chromi | Difficult to justify extent of improvement from previous work Limits to sensitivity of detection |
| Biofertiliser - Engineering nitrogen fixation pathways in non-leguminous plants | Food and Nutrition | Potential to be adapted for widespread issues such as desertification | Difficult to predict efficacy of system in plant models Biological containment issues |
| Flavivirus Detection - Distinguishing between different mosquito-borne infections via protein detection | Diagnostics | High morbidity in developing countries Non-specific nature of symptoms often delays treatment onset | Similar devices have recently been developed Difficult to improve upon existing diagnostics within given time frame |
Three ideas were subsequently shortlisted:
1. UV Kill Switch
The UV kill switch would be designed as a safety feature to kill bacteria upon exposure to light. Engineered bacteria would thus be contained in labs with UV filters on the windows. It would also make decontamination with UV much more effective by permitting lower intensities than those conventionally used in sterilisation. The kill switch would work by UVR8, a dimer in the dark and a monomer in the presence of UV light. It would be fused to a TetR DNA binding domain so TetR can only bind as a dimer. In the dark, TetR keeps repressing toxin production, however in the light TetR monomerises and the toxin gene is activated.
Pros:
- The UV kill switch wouldn’t require chemical induction
- Very easy to use
- Prevents bacteria from leaving on clothes etc
Cons:
- There are already many kill switches in use for synthetic biology which are very effective for biosafety
- It wouldn’t work if bacteria escaped into dark areas e.g. pipes
- It would require extra equipment in the lab e.g. UV filters and lights which do not emit UV
2. Bioplastics
Single-use plastics are severely harmful to the environment, polluting bodies of water and requiring 100s of year to degrade. While biodegradable alternatives exist, their production has been largely hindered by the inefficiency and high cost of production. We identified that improving the batch processes used currently would be a critical step to make the bioplastic, PHB, feasible for large-scale, sustainable production. Our idea was that by linking an indicator of excess PHB production to cell lysis followed by PHB aggregation, fermentation could become a continuous process which has the potential to replace current approaches.
Pros:
- There is a high demand for bioplastics
- Current approaches use harmful chemicals in purifications
- Premature lysis would be hard to prevent
Cons:
- Bacterial yields are lower than in algae currently
- Many areas of the scaling up currently require improvements before the technology can be used
- Protein would be needed to be removed from the plastic which may lower the efficiency significantly
3. Probiotic Treatment for Epilepsy
There has been a rise in cases of epilepsy in developing countries due to bacteria modifying the microbiome and immune system leading to changes in cytokines spreading to the brain resulting in epilepsy. We saw there was a need for a novel treatment. We proposed to produce medication in response to a seizure via a genetically engineered probiotic in the gut in order to treat the condition as quickly as possible and when it is needed, this also allows the medication to be of a patient-specific dose. We then considered treating the cause of this which is via the development of an autoimmune disease. This led to research of a greater range of autoimmune diseases and generalised treatment and eventually progressed into our chosen project.
Pros:
- Automedication
- Microbiome modification is a growing field
- Serious problem with increasing incidence
Cons:
- Difficult detection of signals
- Time taken to detect and respond to signals may be too slow
Final Project Decision:
A key deciding factor in our final project choice was a survey of the general public which we publicised through our social media. In addition to assessing general awareness of genetic engineering, we asked 128 participants to choose the real-world issues they believed would be the best focus of a synthetic biology project. The results are shown below. After careful consideration of the pros and cons of each project, and taking into account the overwhelming majority of survey participants that picked therapeutics as an area of priority, we decided to target our research towards probiotic treatments.
Further Refinement
Additional research into the pathophysiology and morbidity of epilepsy caused us to reconsider our initial idea. After taking into account the localised action of IL-10 secreted by the probiotic bacteria, we decided to shift our focus to gastrointestinal autoimmune diseases.