Diabetes mellitus 2 therapy - project 2019

Please check out our official iGEM 2019 wiki for further information about our project.

Diabetes mellitus 2 therapy - project 2019

    incretin glp 1 Tap for more details
    Overview over Application
    The aim of the project 2019 is the generation of a probiotic for the therapy of Type II Diabetes Mellitus based on a plasmid chassis incorporating a Cas3 self-kill mechanism to prevent the spread of GMOs in the environment which also addresses the high amount of concerns associated with GMOs and fulfills the necessary biosafety standards. Moreover, the plasmid chassis allows for a controlled use of the probiotic and limits its habitat to that of the human gut due to the incorporation of three different regulators inhibiting the Cas3 self-kill system when the bacterium is located in its designated environment.

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    Simplified representation of our project.
    In the gut, our probiotic is supposed to form and secrete incretin mimetics in response to glucose. The incretin mimetics will be taken up by the enterocytes and are transported to the pancreas via the blood, where they enhance insulin secretion. Since Diabetes is one of the most prevalent diseases nowadays, we address an important and relevant problem not only for the clinics but also for the economy and world wide health situation. In addition to the development of such a GMO we also plan to model the efficiency, stability and kinetics of the self-kill mechanism. Our Cas3 biosafety probiotic chassis can also be used for different applications by exchanging the gene of interest within the plasmid. Therefore, our chassis can be used by researchers who search for a functional chassis which fulfills biosafety standards.

    Type II Diabetes Mellitus and incretin mimetics

    Type II Diabetes Mellitus is a metabolic disease that affects about 10 percent of the population. One of its major symptoms is the relative lack of insulin, which causes a decreased uptake of glucose into cells, leading to an energy crisis. In Type II Diabetes Mellitus the body compensates this relative lack of insulin by secreting more insulin, which causes stress for insulin producing beta cells of the pancreas. This increased stress will, in the end, lead to the destruction of the beta cells, leaving the body with an absolute lack of insulin, making insulin substitution necessary. In Type II Diabetes Mellitus the relative lack of insulin can have multiple reasons. It can be induced by overconsumption of sugar-containing food, decreasing the sensitivity of the Insulin Receptors, as they are downregulated. But it can also have genetic reasons, such as a mutation in an essential gene etc. A form of treatment for Type II Diabetes Mellitus are incretin mimetics. Incretin mimetics copy the incretin effect of incretins such as Glucagon Like Peptide 1. This is the explanation for the fact that oral uptake causes a bigger release of insulin, than the parenteral uptake. Glucagon like peptide 1, produced in the L-cells of the intestine, is secreted upon nutrient availability, and reaches the pancreas through the bloodstream. There it will bind its receptor (a G-protein coupled receptor), which will activate Adenylate Cyclase (if ATP is available within the cell), initiating the production of cAMP. Overall, this will lead to increased Calcium Ion influx, allowing for more Insulin to be secreted from the beta cells. This increased secretion will help overcome a relative lack of insulin in Type II Diabetes Mellitus, if the amount of incretins secreted is sufficient.

    Are gmos good for you?

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    Origin of exendin-4
    Genetically modified organisms (GMOs) are organisms whose genetic information has been altered intentionally with the use of genetic engineering. The technique used and the way of alteration varies between different GMOs and comprises gene knockouts and knockins as well as enhancement or repression of gene expression. GMOs open up many possibilities for basic research, food production, industry and treatment or diagnosis of diseases. Concerns about GMOs have been raised by many people and especially address their safety when intentionally or unintentionally released into the environment. Therefore, efforts have been made and are still made towards ensuring the biosafety of GMOs. There are a lot of benefits of genetic engineering in medicine

    iGEM Drylab - Synthetic biology bioinformatics

    While our biocontainment strategy relies on the Class I Type I CRISPR system, we will utilize CRISPR/Cas9 technology for the construction of the chassis. CRISPR/Cas9 (or similar) technology has become a versatile toolkit for gene editing in all domains of life. Despite of the successes, off-target activities can be observed in many cases. These off-target activities lead to unwanted genome alterations when non-homologous end joining machineries are available in the system of interest, and therefore have to be considered in every experiment. To facilitate the analysis of experimental off-target identification, we will create a data analysis pipeline for GUIDE-Seq and CIRCLE-Seq experiments to identify off-target sites in CRISPR/Cas9 experiments. Our goal is to generate a reproducible and parallelizable analysis software tool, based on the bioinformatics workflow management system Nextflow. To us, creating an easy-to-use software tool is of highest priority. Thus, we are creating a clear and comprehensible graphical user interface. We plan to improve the existing workflow layout by replacing single components to improve the accuracy of the result, and to reduce the computational time needed. Furthermore, we will validate the results of our workflow experimentally, and will integrate the results of our software tool into our wet-lab experiments. We will encourage other iGEM teams and research groups, who are working with CRISPR/Cas9 systems, to use our tool.

Synthetic biology software - iGEM Tübingen

Bioinformatics software

Throughout our participations in iGEM several software tools have been developed. Read more about them and find download instructions here.

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iGEM Tübingen - Gallery

iGEM Tübingen - Gallery

A gallery of our various iGEM teams, presentations and awesome projects.

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