Team:Goettingen/project overview/diganosis

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        <h3>Project</h3>
 
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        <ul>
 
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        <li><a href="https://2014.igem.org/wiki/index.php?title=Team:Goettingen/project_overview">Background</a></li>
 
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<ul>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview">The global burden of fungal infections</a></li>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/fungal_infections">Fungal infections</a></li>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/current_tools">Current diagnostic tools</a></li></ul>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/project">Our project!</a></li>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/perspectives">Further perspectives</a></li>
 
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<ul>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/diganosis">Diagnosis</a></li>
 
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/therapeutics">Therapeutics</a></li></ul>
 
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  <div id="goenext"><a id="prev"><img id="pButton"></a> 13/15 <a id="next"><img id="nButton"></a></div>     
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<br /><br /><br />
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      <h1>Applications in Diagnostics</h1>      <br />   
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<h2>Lowering costs and the burden</h2><br />
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<p>The attachment of a chemical moiety that emits a quantifiable signal (a
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        <li><a href="https://2014.igem.org/Team:Goettingen/project_overview/project_gallery">Gallery</a></li>
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fluorescent, enzymatic or luminiscent moiety) to our peptides can lead to an
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/project_drylab">Dry lab</a></li>
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<li><a href="https://2014.igem.org/Team:Goettingen/project_overview/project_wetlab">Wet lab</a></li>
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alternative diagnostic method to antibody and antibody fragments with the added
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      <h1 >Background</h1>
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      <h2 id="global_burden">The global burden of fungal infections</h2>      <br />
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    <p>Fungal pathogens are a major public health threat with significant global effects which, surprisingly, is not being addressed as it should. Globally, around 1.5 million people die each year of invasive fungal infections and the number of people who die each year from the top 10 invasive fungal diseases is at least equal to those dying from tuberculosis or malaria. Moreover, the mortality rate of invasive fungal infections is usually greater than 50%.</p><br><p>In contrast, funding for medical mycology is highly underrepresented, accounting for 1.4-2.5% of the total of what the Wellcome Trust, the U.K. Medical Research Council and the U.S. National Institutes of Health spent in 5 years during the late 2010s. This underrepresentation could be just an effect of the number of applications for funding in the area, but even so, the need for an increased awareness and engagement by funding institutions and researchers is no less urgent: the development of new diagnostic and therapeutic tools is critical to improve the situation of high-risk patients.</p>
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<br />
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<h2 id="fungal_inf">Fungal infections and current diagnostic tools</h2>
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<p>The most common fungal infections are superficial skin, nails and mucosal infections, which are caused in most cases by fungi of the genus <i>Candida</i>. These infections are usually not life threatening and have such common manifestations as athlete's foot and vulvovaginal candidiasis.</p>
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benefit of the relative low cost of production and modification of small peptides. This cost reduction may
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<br /><p>Invasive fungal infections, on the other hand, have unacceptably high mortality rates. Patients with a compromised immune system -such as AIDS patients and post-transplantation patients taking immunosupresants- are at special risk as they don't have the usual barriers that prevent invasive infections in healthy individuals.</p><br />
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<p>According to Brown, <i>et al</i>., (2012), more than 90% of the reported deaths caused by fungi are associated with species from four genera: <i>Cryptococcus</i>, <i>Candida</i>, <i>Aspergillus</i> and <i>Pneumocystis</i>, but epidemiological data for fungal infections is poor, as these infections are often misdiagnosed and there is a lack of accurate data from the developing world.</p><br />
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<h3>Endemic dimorphic fungosis</h3><br />
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help to spread this diagnostic tool to the markets of the developing world, where
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<p> The following map is an adaptiation of the information presented in Brown, <i>et al</i>., (2012), where the authors make some comments regarding the quality of that information: 1) the data is extrapolated from a few and geographically localized studies and 2) accurate data is lacking from the developing world and the calculations may underestimate the true values of the presented statistics.</p><br />
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fungal infections have the largest mortality rates and were health care is
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largely affected by economic constraints. Moreover, if the peptides prove to have a high species-specificity, the diagnosis based on them may give more information for a proper therapy choice, potentially reducing the toxicity risks associated with the use of broad spectrum antimycotics.</p><br />
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<h2><i>In vivo</i> diagnosis and the potential of artificial selection</h2><br />
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<p>Short peptides are currently being used as diagnostic tools for certain kind
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      {name: '<b>Disease:</b> Penicilliosis<br><b>Pathogen:</b><i> Penicillium marneffei</i><br><b>Region:</b> Southeast Asia<br><b>Est. life-threatening infections per year</b>: >8,000', latitude: 10.1333, longitude: 102.7000, radius: 8, fillKey: 'gt50'},
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      {name: '<b>Disease: </b>Histoplasmosis<br><b>Pathogen:</b><i> Histoplasma capsulatum</i><br><b>Region:</b> Midwestern United States<br><b>Est. life-threatening infections per year</b>: ~25,000', latitude: 40.5, longitude: -85, radius: 25, fillKey: 'gt50'},
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      {name: '<b>Disease:</b> Coccidioidomycosis<br><b>Pathogen:</b><i> Coccidioides immitis</i><br><b>Region:</b> Southwestern United States<br><b>Est. life-threatening infections per year</b>: ~25,000', latitude: 39, longitude: -115.5, radius: 25, fillKey: 'gt50'},
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{name: '<b>Disease:</b> Blastomycosis<br><b>Pathogen:</b><i> Blastomyces dermatitidis</i><br><b>Region:</b> Midwestern and Atlantic United States<br><b>Est. life-threatening infections per year</b>3: ~3,000', latitude: 37, longitude: -80, radius: 3, fillKey: 'gt51'},
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of cancers. These peptides are naturally produced by humans
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{name: '<b>Disease:</b> Paracoccidioidomycosis<br><b>Pathogen:</b><i> Paracoccidioides brasiliensis</i><br><b>Region:</b> Brazil<br><b>Est. life-threatening infections per year</b>: ~4,000', latitude: -15.7833, longitude: -47.8667, radius: 4, fillKey: 'gt50'},
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and have their natural binding proteins in the surface of cells; however, they
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natural target, and they also have been modified with radionuclides that make it
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possible to detect the location of tumors -cells were their binding proteins are
 +
overrepresented- with PET or SECT imaging.</p><br />
 +
<p>The most common isotopically labelled peptide used for diagnosisis a <sup>111</sup>In-labelled somatostatin analogue, known as OctreoScan<sup>TM</sup>, which is used to diagnose a variety of tumors. Other peptides under
-
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develompent are cholecystokinin/gastrin analogues, glucagon-like peptide-1,
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<br />
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bombesin, chemokine receptor CXCR4 targeting peptides, RGD peptides, exendin,
 +
Substance P, LHRH, neurotensin, &alpha;-M2, &alpha;-M2H and VIP.</p>  <br />
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<p>Following the same rationale, our artificially selected peptides can be modified and optimized to increase their binding affinity and their half-life. The peptides can then be tagged with radionuclides to enable the diagnosis by imaging techniques. The results of such a diagnostic method will give more information about the localization and spread of the fungal infection inside the patient's body than any of the currently available diagnostic methods.</p><br /><br />
 +
<hr>
 +
<br />
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<h2>References</h2><br />
 +
<ul>
 +
<li>1. Fani, M., et al., (2012), Radiolabeled peptides: valuable tools for the detection and treatment of cancer, <i>Theranostics</i>, 2(5).</li><br />
 +
<li>2. Laverman, P., (2012), Radiolabelled peptides for oncological diagnosis, <i>Eur J Nucl Med Mol Imaging</i>, 39 (Suppl I).</li>
 +
</ul>
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<h2>Our project: paving the way for new diagnostic and therapeutic tools</h2>
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    <p>
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  Our aim is to develop a diagnostic technique capable of detecting the presence of fungal pathogens in  a sample collected from a patient. Briefly, our approach is as follows. Through a yeast two-hybrid assay we will select a set of peptides that show affinity towards surface proteins from different fungi (<i>Aspergillus nidulans</i>, <i>A. fumigatus</i>, <i>Candida albicans</i> and <i>C. glabrata</i>). After confirming the interaction between the surface proteins and a given peptide, we intend to attach a molecule to the peptide marker. In our project, this molecule will be a fluorescent protein, but in principle can also be an immune system activator which is then recognized by the immune cells or other chemical moiety that adds novel functionalities or increases the peptide stability. In comparison to antibodies or antibody fragments, peptides are small, easily synthesized, modified less expensively and show higher diffusion rates in tissues. We expect our method to be faster, more accurate and cheaper than other existing methods. Other laboratories may follow our approach to generate and refine their own peptides with specificity towards their proteins of interest.
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Latest revision as of 11:20, 2 October 2014

Project

13/15



Applications in Diagnostics


Lowering costs and the burden


The attachment of a chemical moiety that emits a quantifiable signal (a fluorescent, enzymatic or luminiscent moiety) to our peptides can lead to an alternative diagnostic method to antibody and antibody fragments with the added benefit of the relative low cost of production and modification of small peptides. This cost reduction may help to spread this diagnostic tool to the markets of the developing world, where fungal infections have the largest mortality rates and were health care is largely affected by economic constraints. Moreover, if the peptides prove to have a high species-specificity, the diagnosis based on them may give more information for a proper therapy choice, potentially reducing the toxicity risks associated with the use of broad spectrum antimycotics.


In vivo diagnosis and the potential of artificial selection


Short peptides are currently being used as diagnostic tools for certain kind of cancers. These peptides are naturally produced by humans and have their natural binding proteins in the surface of cells; however, they have been optimized to increase their half-life and their affinity towards their natural target, and they also have been modified with radionuclides that make it possible to detect the location of tumors -cells were their binding proteins are overrepresented- with PET or SECT imaging.


The most common isotopically labelled peptide used for diagnosisis a 111In-labelled somatostatin analogue, known as OctreoScanTM, which is used to diagnose a variety of tumors. Other peptides under develompent are cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin, chemokine receptor CXCR4 targeting peptides, RGD peptides, exendin, Substance P, LHRH, neurotensin, α-M2, α-M2H and VIP.


Following the same rationale, our artificially selected peptides can be modified and optimized to increase their binding affinity and their half-life. The peptides can then be tagged with radionuclides to enable the diagnosis by imaging techniques. The results of such a diagnostic method will give more information about the localization and spread of the fungal infection inside the patient's body than any of the currently available diagnostic methods.




References


  • 1. Fani, M., et al., (2012), Radiolabeled peptides: valuable tools for the detection and treatment of cancer, Theranostics, 2(5).

  • 2. Laverman, P., (2012), Radiolabelled peptides for oncological diagnosis, Eur J Nucl Med Mol Imaging, 39 (Suppl I).


13/15

Retrieved from "http://2014.igem.org/Team:Goettingen/project_overview/diganosis"