Team:CSU CHINA/Proof Of Concept
Description
Type I diabetes is this kind of disease that due to the destruction of Islet b cells, the secretion of insulin is absolute deficient, which directly leads to Type I diabetes. As one kind of diabetes, the amounts of Type I is only 5% of total diabetes patients.
Fig1.Age Distribution of T1DM in the global population
However, as we can see from this figure above, most of Type I patients get sick at their childhood or adolescence, parts of adult can also have an attack. Approximately 80 to 90 percent child diabetes patients are patients of Type I.
Fig2.Epidemology of T1DM in 13 regions of China
The global incidence rate of Type I is on a rise According to World Health Organization, the incidence rate in China is 0.59 per million.
Various of factors can be dangerous factors of Type I including Genetic, toxins, immune system disorder and viral infection.
Genetically, the consistency of type I in identical twins can be up to 50%, if one of the parents is the patient of type I, the risk their offspring should take is only 2 to 5 percent. Toxins like Rodenticide and viruses like mumps virus can also increase the possibility of getting sick.
Meanwhile, due to the disorder of immune system , islet beta cells are severely destroyed, insulin secretion is in absolute deficiency, thus the blood glucose rises, then leads to type I.
Multiple complication can be caused by type I including acute ketoacidosis and chronic diabetic foot and other complications implicating other systems and organs.
Current treatment is mainly consist of drug therapy and surgical transplantation. For drug therapy, patients need to take several injection a day to maintain the blood glucose steady or continuous subcutaneous injection with insulin pump. Both methods requires lifetime use. This would cause some side effects like pain at injection site and subcutaneous adipose hyperplasia.
Surgical transplantation for pancreas, islet and stem cells can solve the problem once and for all,but immune reaction and the scarcity of resources can not be ignored. Based on these, we designed our project: Sweet Guard.
Fig3.Design
This figure above can illustrate our integrated design. Plasmids we use contains domain VP16, GAL4, Lov and GI. Former 2 are the Yeast-hybrid system, latter 2 comes from Photoreceptor genes that control plant phototropism in Arabidopsis thaliana.
When the concentration of blood glucose rises, glucose induced promoter would have a high-level expression. Expose these engineered cells under the blue light at this time, these cells would be able to activate the downstream insulin expression and secrete insulin. The only secretion itself is not enough, the over secretion would occur if there is nothing to stop it and it will be dangerous for patients. In order to avoid this dangerous situation fro happening, a brake system is designed. This brake system will be activated when insulin receptor senses the insulin concentration reaching a certain level and will stop the secretion.
To implant the engineered cell under the skin, we can use materials like micro-capsule, hollow fiber membrane tube, sodium alginate glue as carriers to realize the abdomen or subcutaneous transplantation to reach the goal of controlling blood sugar and minimizing the side effect at the same time. What we want to realize is to test the blood glucose with glucose meter and control the secretion of insulin with blue light. we want to realize the whole work flow with a smart bracelet -like equipment.
Reference
[1] Weng J, Zhou Z, Guo L, Zhu D, Ji L, Luo X, Mu Y, Jia W; T1D China Study Group. Incidence of type 1 diabetes in China, 2010-13: population based study. BMJ. 2018 Jan 3;360:j5295. doi: 10.1136/bmj.j5295. PMID: 29298776; PMCID: PMC5750780.