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BioIQS

We are the BioIQS iGEM team!

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Project description

We would like to present you a brief description of our project on celiac disease:

Our project is based on the design of a personalized gluten sensor by using the common tools of synthetic biology. There are already several sensors that are able to detect gluten in the food. However, there are milestones that still have not been overcome. We propose a robust model in which the HLA molecule of a patient is expressed and used as a sensor to detect specific reactive gluten epitopes.

Coeliac disease (CD) is an autoimmune disorder that is closely related with HLA (Human leukocyte antigen), a type of receptor that are located in the surface of almost every cell of a human tissue, including white blood cells. These molecules are responsible for the correct discrimination between what is self and foreign proteins, guaranteeing the correct immune response against foreign agents that can cause infections.

Within the HLA protein family there are the highly polymorphic HLA-DQ, which means that there are a lot of existing genetic variants of these molecules. Some of these HLA-DQ variants are able to recognize different gluten epitopes (aminoacid sequence of a protein) and present them to the T cells. More specifically, 25% of the general population carry the HLA-DQ that can recognize gluten derived epitopes, but only 1% of the population suffer from coeliac disease. The reason of such fact is that the inflammatory reaction is triggered by some T cells that can sense the gluten epitope presented by the HLA-DQ.

Understanding why the inflammatory response is triggered by a certain type of T cells upon epitope presentation by HLA-DQ molecules is essential to uncover the mechanism of CD. Since the first step for the immune response activation is the recognition and binding of the gluten epitope to the HLA-DQ receptor, the development of a personalized sensor to determine reactive epitopes could help to better understand the disease and would also allow the screening of those foods that could potentially trigger an immune response to the patient.

Objectives

In our iGEM Project we will design a personalized gluten sensor through a synthetic biology approach. To do so, we decided to build a model based on the HLA expression of the patient which will be coupled to a sensor, allowing the detection of reactive epitopes. The main specificities of our sensor are described as follows:

  • Since our sensor will be built according to the patient HLA, it will allow the detection of specific reactive epitopes independently of the food source.
  • Additionally, our sensor will be able to detect reactive epitopes even in fermented foods.
  • The methodology implemented in our sensor could be used for the identification of new reactive epitopes and unknown allelic variants.
  • Our design requires only a DNA sample of the patient. Therefore, the methodology and application of our sensor could be extended for the detection of other HLA related disorders as well as the generation of new research lines for the diagnosis, detection and basic knowledge of these type of disorders.

footer, written by BioIQS iGEM team