In recent years, cardiovascular disease is becoming the most severe cause of death worldwide. Considering that hyperglycemia, diabetes, and hypertension are all risk factors for developing cardiovascular disease, current therapies indirectly prevent and protect against cardiovascular disease by introducing engineered bacteria that secrete glucagon-like peptide 1 (GLP-1) and leptin to lower blood glucose levels and suppress hunger(Sedlmayer F et al.,2018).
Our team, SCU-China, is working on developing an engineered probiotic platform that can be colonized in the gut while also giving the platform therapeutically relevant functions downstream. Through the CCiC and subsequent exchanges, we learned that HZAU-China's project this year is related to the secretion of substances by engineered probiotics to mitigate thrombosis and protect blood vessels.
Thus, our two teams led a series of collaborations and built a strong partnership. Our team helped HZAU-China to characterize the expression of trimethylamine dehydrogenase (TMADH), an enzyme that degrades trimethylamine (TMA). Based on the success of the characterization, we introduced it into our engineered probiotics to accomplish a more specific cardiovascular disease prevention effect.
1. Recommending more experiments to address the issue of colonization by engineered
probiotics, like collecting feces from the intestine;
2. Mentioning that the environment in the intestine is very complex, and some physical
models can simulate the elution rate of the intestinal flora;
3. Considering the effects of osmolarity and population induction in the model, beyond the
metabolic level;
4. Recommending using measured kinetic parameters from experiments rather than from the
articles, making it much more convincing.
1. Recommending that enzymes from the core metabolic pathway for transforming TMA to MMA,
TMADH, DMADH, and FdnH, be introduced into the same plasmid for expression and product
determination. Also, the measurement should not be limited to HPLC, but should include RNA
level and protein level additionally;
the corresponding section of our results here
2. Giving solutions for some problems with the operation of EcN and possible experimental
problems;
3. Considering using bioinformatic models to simulate the absorption of drugs in the
intestine and into the bloodstream to better tailor microbial colonization and product
yield;
4. Analyzing whether the expression of the target is sufficient to produce a therapeutic
effect;
5. Considering biosafety, such as designing suicide switches to prevent engineered microbes
from entering the natural world.
Considering that our two teams were similar in thoughts, we had an in-depth exchange on the market acceptance of the product, its market prospect, and the final shape it would present.
SCU-China thinks that HZAU-China needs to investigate patients' demands further, conduct a cost analysis of existing drugs and health products, and communicate more deeply with relevant enterprises. HZAU-China thinks that SCU-China needs to communicate deeper with relevant enterprises, investigating related probiotic products and the industry situation of erythritol further.
Before we used ppt to explain our project to judges or professional professors, their team put forward valuable suggestions on the format and layout of our ppt. We also exchanged many presentation skills together.
Fig 1. Our PPT
During the epidemic, team members can only communicate and cooperate online. To make teamwork more efficient, the two teams jointly explored and exchanged online collaboration tools and meeting platforms and finally found more convenient and useful tools for teamwork.
1. Sedlmayer F, Aubel D, Fussenegger M. Synthetic gene circuits for the detection, elimination and prevention of disease. Nat Biomed Eng. 2018;2(6):399-415. doi:10.1038/s41551-018-0215-0