Team:SUSTech Shenzhen/Description
Why do we want to do the program of engineering bacteria?
As a major health problem in the world, diarrhea causes roughly 11% of death in children under the age of 5 (0.801million)1 . This somewhat results from 780 million people do not have access to safe drinking water and 2.5 billion do not have access to adequate sanitation2. According to WHO, children under the age of three in low-income nations had three bouts of diarrhea per year on average2.
In China, even if diarrhea is no longer a severe problem, it still bothers many people under certain circumstances. For instance, when some people face important moments in life, such as promotion defenses and major exams, unreleasable tension can often lead to diarrhea. And for women, the menstrual period may be also accompanied by diarrhea.
To overcome diarrhea-caused death in sanitation less-developed regions, and to help people around us in trouble of diarrhea, we want to solve this problem from the perspective of engineered bacteria.
Why do we want to use engineering bacteria?
Based on the development of synthetic biology, the clinical application of engineered bacteria has become a reality3. Bacteria interact with the ecological niche in the human body to produce different changes in the course of the disease. Lactobacillus and E. coli are designed to tolerate the immune system and produce therapeutic drugs directly in the intestine4.
What do we want to accomplish?
The objective of our study is in the development of an engineered microbe that regulates water retention through colanic acid biosynthesis, triggered by dehydration cues. We further include the triggered release of broad-spectrum antimicrobial peptides (AMPs) to displace the diarrhea-causing gut pathogens. The specific dehydration cues include sensing for intestinal chloride concentration and pathogenic bacterium quorum-sensing molecules.
There are some potential advantages of our design. Firstly, this is an integral method that could absorb water and clear pathogens simultaneously. Secondly, engineered bacteria may stay for some time after entering the human intestines and continue to exert their efficacy, preventing the occurrence of acute dehydration and repeated infections, so it can reduce the number of times and the demand for medicines. Thirdly, this method may have the potential of playing a preventive role if the patient takes our bacteria before possible diarrhea, such as a menstrual period or nervousness.
Here are several goals we want to achieve:
However, because of the limited time, we could only accomplish some preliminary verification of each part.
Synthetic Biology Side
This project would provide a basic idea for diarrhea treatment through a synthetic biology approach. By the way, it also proposes a method combining experiment and Boolean model to verify the synthetic circuit.
Reference
[1]Liu, L.; Johnson, H. L.; Cousens, S., Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000 (vol 379, pg 2151, 2012). Lancet 2012, 380 (9850), 1308-1308.
[2]Diarrhoeal disease. https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease (accessed Oct 5, 2021).
[3]Riglar, D. T.; Silver, P. A., Engineering bacteria for diagnostic and therapeutic applications. Nature Reviews Microbiology 2018, 16 (4), 214-225.
[4]Duan, F. F.; Liu, J. H.; March, J. C., Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes. Diabetes 2015, 64 (5), 1794-803.