Team:Tuebingen

GLP.exe
GLP.exe - a safe and effective treatment for Type 2 Diabetes Mellitus
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Several treatment options for Type 2 Diabetes Mellitus have been developed in recent years significantly improving the patients' insulin level.

Hence, the diagnosis of Type 2 Diabetes Mellitus is no longer a death sentence.

Yet...
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Current Drugs

are expensive, require fine tuning and daily shots. Moreover, they have severe side-effects, causing patients to skip doses.

“Many patients don’t want to use insulin. They don’t want to do finger sticks and they’re afraid of hypoglycemia.”

“To fight the global Diabetes pandemic, we would ideally have an accessible cost-effective easily-compliant intervention that has high clinical efficacy and that is free of adverse side effects.”

Prof. Harold Lebovitz, State University of New York Health Science Center, Brooklyn, New York

However...
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There's a solution!

Our therapeutic agent is a probiotic secreting incretin mimetics placed in the patients intestine by oral administration of capsules. GLP-1 and Exendin-4, our main actors, cause an increase in insulin secretion, if the cell has already taken up sugar.

This enables an easier therapy where a regular intake of medicals is not required.

Improved cell penetrating peptides with the use of artificial intelligence allow for an efficient and safe transport of our effectors into the cells.

Safety
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is our highest priority!

Therefore, we developed a novel, Cas3 based kill-switch mechanism. The flexible system uses three regulators inspired by the human intestines: temperature, availability of fatty acids in form of Acyl CoA and N-Acetyl-Glucosamin.

If the conditions of our regulatory system are no longer met, Cas3 will be degrading all genetic information.

Additionally
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An in depth E. coli Nissle characterization

Despite the fact that E. coli Nissle is an already approved probiotic, it's surprisingly badly characterized.

Hence, we provide the first metabolic model of E. coli Nissle and optimize it's growth for various growth media. Furthermore, we predicted the interaction and competition of E. coli Nissle with common competitors for various fluxes in the gut.

Finally, we carried out a series of RNA-Seq experiments to assess the adaptions and reactions of E. coli Nissle to aerobic, as well as anaerobic occurring stress factors.

Bringing it all together
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Our work lays the foundation for an innovative, unprecedented approach to treat Type 2 Diabetes Mellitus.