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− | Generally, people who suffer from CIDs need to monitor their conditions closely. This may include <b> frequent and regular hospital visits to measure levels of inflammation and monitor disease progression | + | Generally, people who suffer from CIDs need to monitor their conditions closely. This may include <b> frequent and regular hospital visits </b> to measure levels of inflammation and monitor disease progression. These visits are not only <b> time-consuming </b> but also <b> mentally exhausting </b> to the patients. Not only do the visits remind patients of their illness, but the <b> time spent on transport and testing </b> is a life-long burden to the individual. Current methods for disease tracking are almost exclusively <b> invasive </b> and include blood sampling and, occasionally, more comprehensive procedures such as endoscopy. Invasive methods of testing are not only <b> expensive and unpleasant </b>, but also require well-trained personnel and do not allow the patient to self-monitor, requiring <b> regular hospital visits </b>. Ideally, patients should be tested more often to provide a clear picture of the disease and catch inflammatory changes when they happen. However, the invasive nature of current methods renders testing on a weekly basis impractical and expensive. |
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<div style="font-size: 13px;"> Figure 1: Visual representation of the usage of the CIDosis patch and the engineering and scientific approach. 1: The patch collecting sweat from the skin. 2: The layers in the patch. 3: The scientific receptor engineering. 4: The patch after it has changed color. 5: The image-analyzing app. </div> | <div style="font-size: 13px;"> Figure 1: Visual representation of the usage of the CIDosis patch and the engineering and scientific approach. 1: The patch collecting sweat from the skin. 2: The layers in the patch. 3: The scientific receptor engineering. 4: The patch after it has changed color. 5: The image-analyzing app. </div> | ||
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− | Our project is founded on previous research showing the presence of interleukins IL-1β, IL-6 or IL-10 (ILs) in sweat <a href="#katch" aria-describedby="footnote-label" id="katch-ref"> </a> <a href="#hladek" aria-describedby="footnote-label" id="hladek-ref"> </a>, and the correlation with their respective levels in blood <a href="#marq" aria-describedby="footnote-label" id="marq-ref"> </a>. The CIDosis patch implementation is based on an engineered <i>Saccharomyces cerevisiae </i> (Baker’s yeast) biosensor capable of detecting the inflammation markers IL-1, 6 and 10. Incorporation of modified Human Interleukin receptors in yeast are backed by previous research showing successful expression of soluble IL receptors in yeast <a href="#voll" aria-describedby="footnote-label" id="voll-ref"> </a>. The activation of the biosensor leads to the expression of a pigment biosynthesis gene and further to the accumulation of a colored compound. The biosensor will be located inside a patch specifically designed to sit on the skin and continuously collect sweat from the user for up to 24 hours. Once interleukins from the sweat reach the patch, our yeast receptors will sense their presence, and produce the aforementioned colored pigment corresponding to the level of the IL in question. | + | Our project is founded on previous research showing the <b> presence of interleukins IL-1β, IL-6 or IL-10 (ILs) in sweat </b> <a href="#katch" aria-describedby="footnote-label" id="katch-ref"> </a> <a href="#hladek" aria-describedby="footnote-label" id="hladek-ref"> </a>, and the correlation with their respective levels in blood <a href="#marq" aria-describedby="footnote-label" id="marq-ref"> </a>. The CIDosis patch implementation is based on an <b> engineered <i>Saccharomyces cerevisiae </i> (Baker’s yeast) biosensor </b> capable of detecting the inflammation markers IL-1, 6 and 10. Incorporation of modified Human Interleukin receptors in yeast are backed by previous research showing successful expression of soluble IL receptors in yeast <a href="#voll" aria-describedby="footnote-label" id="voll-ref"> </a>. The activation of the biosensor leads to the expression of a pigment biosynthesis gene and further to the accumulation of a colored compound. The biosensor will be located inside a patch specifically designed to sit on the skin and continuously collect sweat from the user for up to 24 hours. Once interleukins from the sweat reach the patch, our yeast receptors will sense their presence, and produce the aforementioned colored pigment corresponding to the level of the IL in question. |
</br></br> | </br></br> | ||
The biosensor design (Fig. 1) relies on the <b> dimerization of modified human IL receptors on the yeast plasma membrane upon activation by their respective ligands </b>. The modified receptors contain a <b> synthetic transcription factor </b> bound on their intracellular side that can be released upon dimerization of the receptors. Specifically, dimerization of the receptors leads to the <b> co-localization of two halves of a split-actuator protein </b>, which, when re- united, leads to <b> cleavage of the protein </b> resulting in the release of the transcription factor. The synthetic transcription factor, in turn, binds a specific synthetic promoter and finally activates the <b> expression of the colorimetric reporter gene </b>. | The biosensor design (Fig. 1) relies on the <b> dimerization of modified human IL receptors on the yeast plasma membrane upon activation by their respective ligands </b>. The modified receptors contain a <b> synthetic transcription factor </b> bound on their intracellular side that can be released upon dimerization of the receptors. Specifically, dimerization of the receptors leads to the <b> co-localization of two halves of a split-actuator protein </b>, which, when re- united, leads to <b> cleavage of the protein </b> resulting in the release of the transcription factor. The synthetic transcription factor, in turn, binds a specific synthetic promoter and finally activates the <b> expression of the colorimetric reporter gene </b>. |
Revision as of 13:54, 25 October 2020
![](https://static.igem.org/mediawiki/2020/6/6f/T--UCopenhagen--descriptionpage-cover-photo.jpg)
Project description
& inspiration
![](https://static.igem.org/mediawiki/2020/7/75/T--UCopenhagen--descriptionpage-pic-1-1.png)
Defining the problem
Chronic inflammatory diseases (CIDs), such as juvenile and adult rheumatoid arthritis, asthma and inflammatory bowel disease, are life-long , debilitating illnesses, where patients suffer from chronic pain, fatigue, swelling and fever . Due to the complicated disease profiles, treatments for CIDs do not always work and there is usually a long search process for the right treatment .
Generally, people who suffer from CIDs need to monitor their conditions closely. This may include frequent and regular hospital visits to measure levels of inflammation and monitor disease progression. These visits are not only time-consuming but also mentally exhausting to the patients. Not only do the visits remind patients of their illness, but the time spent on transport and testing is a life-long burden to the individual. Current methods for disease tracking are almost exclusively invasive and include blood sampling and, occasionally, more comprehensive procedures such as endoscopy. Invasive methods of testing are not only expensive and unpleasant , but also require well-trained personnel and do not allow the patient to self-monitor, requiring regular hospital visits . Ideally, patients should be tested more often to provide a clear picture of the disease and catch inflammatory changes when they happen. However, the invasive nature of current methods renders testing on a weekly basis impractical and expensive.
Conclusively, suffering from a chronic inflammatory disease can be extremely exhausting both physically and mentally. Although wide research is being conducted in regards to the treatment of all types of inflammatory diseases, not many monitoring devices exist to make life easier for the individual living with a CID, and provide continuous tracking of their condition. In order to improve the quality of life for patients worldwide, we have created CIDosis.
Our Solution
With CIDosis, we aim to improve the quality of life of patients, by providing a non-invasive device that will allow CID patients to monitor their own inflammation status from the comfort of their home. Our device consists of a patch that detects the levels of inflammatory markers in the sweat. This patch will be placed on the patient’s skin, where it will continuously collect sweat during the day , resulting in a color output reflecting the inflammatory status . The intensity of the color will correlate with the inflammation level. By employing a dedicated app, the patient will be able to track the color intensity using the camera of their mobile phone.
Our self-monitoring patch , CIDosis, is an easy-to-use, non-invasive device, suitable for home use, and will decrease the need for frequent hospital visits , thereby making life easier for the patients. It allows for transparency for the patient regarding their disease progression and is a tool that can help them discover the best self-management strategy for their disease. Not only can it alleviate the burden of hospital visits, but it can provide valuable information on the therapeutic efficacy of certain drugs, allowing for faster treatment adjustments and continuous dosage regulations as the disease progresses.
We envision the use of this patch as a future self-monitoring system for patients suffering from chronic inflammatory diseases worldwide. With the CIDosis patch they have access to a cheap, non-invasive method to measure their daily inflammation and track their condition in an easy way. The utility of such a device is extensive and can alleviate the struggles of many patient groups from Crohn’s disease to Rheumatoid Arthritis.
![](https://static.igem.org/mediawiki/2020/4/4b/T--UCopenhagen--descriptionpage-pic-2.png)
![](https://static.igem.org/mediawiki/2020/1/13/T--UCopenhagen--descriptionpage-pic-3.jpg)
Scientific approach
![](https://static.igem.org/mediawiki/2020/7/74/T--UCopenhagen--descriptionpage-biorender-inflammationmonitor.png)
Figure 1: Visual representation of the usage of the CIDosis patch and the engineering and scientific approach. 1: The patch collecting sweat from the skin. 2: The layers in the patch. 3: The scientific receptor engineering. 4: The patch after it has changed color. 5: The image-analyzing app.
Our project is founded on previous research showing the presence of interleukins IL-1β, IL-6 or IL-10 (ILs) in sweat , and the correlation with their respective levels in blood . The CIDosis patch implementation is based on an engineered Saccharomyces cerevisiae (Baker’s yeast) biosensor capable of detecting the inflammation markers IL-1, 6 and 10. Incorporation of modified Human Interleukin receptors in yeast are backed by previous research showing successful expression of soluble IL receptors in yeast . The activation of the biosensor leads to the expression of a pigment biosynthesis gene and further to the accumulation of a colored compound. The biosensor will be located inside a patch specifically designed to sit on the skin and continuously collect sweat from the user for up to 24 hours. Once interleukins from the sweat reach the patch, our yeast receptors will sense their presence, and produce the aforementioned colored pigment corresponding to the level of the IL in question.
The biosensor design (Fig. 1) relies on the dimerization of modified human IL receptors on the yeast plasma membrane upon activation by their respective ligands . The modified receptors contain a synthetic transcription factor bound on their intracellular side that can be released upon dimerization of the receptors. Specifically, dimerization of the receptors leads to the co-localization of two halves of a split-actuator protein , which, when re- united, leads to cleavage of the protein resulting in the release of the transcription factor. The synthetic transcription factor, in turn, binds a specific synthetic promoter and finally activates the expression of the colorimetric reporter gene .
Our vision is a modular design , allowing for easy swap of the interleukin receptor in the yeast, so the patch can be tailored to the need of the individual patient group. The yeast is powered by designed receptors that boast very high sensitivity and selectivity , coupled with an efficient pheromone pathway for signal amplification . The patch can be photographed with a specialized app to analyze the exact level of coloration regardless of light conditions.
- JoAnne Epping-Jordan, Robert Beaglehole, Catherine Le Galès-Camus, et al. Preventing chronic diseases: a vital investment. 2005. WHO global report. ↩
- Pahwa R, Goyal A, Bansal P, et al. Chronic Inflammation. 2020 Jul 4. Treasure Island (FL): StatPearls [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493173/↩
- Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-1832. doi:10.1038/s41591-019-0675-0↩
- Katchman BA, Zhu M, Blain Christen J, Anderson KS. Eccrine Sweat as a Biofluid for Profiling Immune Biomarkers. Proteomics Clin Appl. 2018;12(6):e1800010. doi:10.1002/prca.201800010↩
- Marques-Deak A, Cizza G, Eskandari F, et al. Measurement of cytokines in sweat patches and plasma in healthy women: validation in a controlled study. J Immunol Methods. 2006;315(1-2):99-109. doi:10.1016/j.jim.2006.07.011↩
- Hladek MD, Szanton SL, Cho YE, et al. Using sweat to measure cytokines in older adults compared to younger adults: A pilot study. J Immunol Methods. 2018;454:1-5. doi:10.1016/j.jim.2017.11.003 ↩
- Vollmer P, Peters M, Ehlers M, et al. Yeast expression of the cytokine receptor domain of the soluble interleukin-6 receptor. J Immunol Methods. 1996;199(1):47-54. doi:10.1016/s0022-1759(96)00163-9 ↩