Team:Goettingen/project overview/fungal infections

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Revision as of 13:05, 5 September 2014

Project

Background

Fungal infections and current diagnostic tools

The most common fungal infections are superficial skin, nails and mucosal infections, which are caused in most cases by fungi of the genus Candida. These infections are usually not life threatening and have such common manifestations as athlete's foot and vulvovaginal candidiasis.

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.

According to Brown, et al., (2012), more than 90% of the reported deaths caused by fungi are associated with species from four genera: Cryptococcus, Candida, Aspergillus and Pneumocystis, 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.

Endemic dimorphic fungosis

The following map is an adaptiation of the information presented in Brown, et al., (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.

Our project: paving the way for new diagnostic and therapeutic tools

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 (Aspergillus nidulans, A. fumigatus, Candida albicans and C. glabrata). 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.

@@ Line 36: / Line 36: @@
 <!-- right column-->
 	<div class="rightpart" id="rpart1">
-        <h1 >Background</h1>
+        <h2 id="fungal_inf">Fungal infections and current diagnostic tools</h2>
-       <h2 id="global_burden">The global burden of fungal infections</h2>       <br />
-    <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>
+<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>
+<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 />
+<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 />
+<h3>Endemic dimorphic fungosis</h3><br />
+<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 />
+<div id="container1" style="position: relative; width: 650px; height: 350px;"></div>
+     <script>
+       //basic map config with custom fills, mercator projection
+      var map = new Datamap({
+        scope: 'world',
+        element: document.getElementById('container1'),
+        projection: 'mercator',
+        fills: {
+          defaultFill: 'rgba(217,225,179,0.9)',
+          gt50: 'red',
+	gt51: 'rgba(46,71,198,0.9)',
+        },
+      })
+       //bubbles, custom popup on hover template
+     map.bubbles([
+       {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'},
+       {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'},
+       {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'},
+{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'},
+{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'},
+     ], {
+       popupTemplate: function(geo, data) {
+         return "<div class='hoverinfo'><p>"+ data.name + "</p></div>";
+       },
+     });
+     </script>
+<br />
+<div id="container2" style="position: relative; width: 650px; height: 350px;">
+<script>
+var diameter = 500,
+    format = d3.format(",d"),
+    color = d3.scale.category20c();
+var bubble = d3.layout.pack()
+    .sort(null)
+    .size([diameter*.8, diameter*.8])
+    .padding(1.5);
+var svg = d3.select("#container2").append("svg")
+    .attr("width", diameter*2)
+    .attr("height", diameter)
+    .attr("class", "bubble")
+.attr("id","svgfig");
+// disease title
+svg.append("text")
+  .attr("id", "disease")
+  .attr("x", 400)
+  .attr("y", 80)
+  .style("font-size", "32px")
+  .style("text-anchor", "left")
+  .text("Disease");
+// organism
+svg.append("text")
+  .attr("id", "organism")
+  .attr("x", 400)
+  .attr("y", 110)
+  .style("text-anchor", "left")
+.style("font-size", "12px")
+  .text("Organism");
+// life threatening infections
+svg.append("text")
+  .attr("id", "lifeThreat")
+  .attr("x", 400)
+  .attr("y", 170)
+  .style("text-anchor", "left")
+.style("font-size", "12px")
+  .text("Est. life threatening infections per year worldwide");
+// mortality rates
+svg.append("text")
+  .attr("id", "mRate")
+  .attr("x", 400)
+  .attr("y", 140)
+  .style("text-anchor", "left")
+.style("font-size", "12px")
+  .text("Mortality rates (% in infected populations)");
+d3.json("https://gist.githubusercontent.com/mloera/ba1db753880f52611398/raw/9f73c9094dad24b08802edfd858aca451e0adb7d/flare.json", function
+(error, root) {
+  var node = svg.selectAll(".node")
+      .data(bubble.nodes(classes(root))
+      .filter(function(d) { return !d.children; }))
+    .enter().append("g")
+      .attr("class", "node")
+      .attr("transform", function(d) { return "translate(" + d.x + "," + d.y+
+")"; });
+  node.append("title")
+      .text(function(d) { return d.className + ": " + format(d.value); });
+  node.append("circle")
+      .attr("r", function(d) { return d.r; })
+      .style("fill", d3.rgb(203,234,247))
+.on("mouseover", function(d) {
+      d3.select("#disease").text(d.className);
+      d3.select("#organism").text(d.organism);
+      d3.select("#lifeThreat").text(d.lifeThreat);
+      d3.select("#mRate").text(d.mRate);
+      });
+  node.append("text")
+      .attr("dy", ".3em")
+      .style("text-anchor", "middle")
+      .text(function(d) { return d.className.substring(0, d.r / 3); });
+});
+// Returns a flattened hierarchy containing all leaf nodes under the root.
+function classes(root) {
+  var classes = [];
+  function recurse(name, node) {
+    if (node.children) node.children.forEach(function(child) { recurse
+(node.name, child); });
+    else classes.push({packageName: name, className: node.name, organism:
+node.organism, lifeThreat: node.lifeThreat, value: node.size, mRate: node.mRate
+});
+  }
+  recurse(null, root);
+  return {children: classes};
+}
+d3.select(self.frameElement).style("height", diameter + "px");
+</script></div><br />
+	<h2>Our project: paving the way for new diagnostic and therapeutic tools</h2>
+    <p>
+   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.
+    </p>
+    </div>
 <!-- end of right column-->
 	</div>