Difference between revisions of "Team:UI Indonesia/Project"

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   <h5>Diphtheria is becoming a prominent issue in Indonesia as its incidence is increasing recently. It also causes various complications, leading to morbidity and mortality. We realized the urgency of fast, reliable, and cheap early detection method for diphtheria infection as one of means necessary for its eradication. Therefore, we created a chimeric between native Escherichia coli Tar chemotaxis receptor and human HB-EGF receptor so the bacterium may recognize diphtheria toxin. Moreover, we combined CheA and CheY in E. coli chemotaxis system with LuxAB and eYFP, respectively. When in contact, LuxAB and eYFP create resonance energy transfer system in which LuxAB gives its emission to eYFP. Without diphtheria toxin, CheA will be in phosphorylated state, allowing interaction with CheY and energy transfer, resulting in yellow color. Toxin binding into chimeric receptor will inhibit CheA phosphorylation, hindering interaction with CheY and energy transfer, resulting in blue color (i.e. LuxAB native color).</h5><br>
 
   <h5>Diphtheria is becoming a prominent issue in Indonesia as its incidence is increasing recently. It also causes various complications, leading to morbidity and mortality. We realized the urgency of fast, reliable, and cheap early detection method for diphtheria infection as one of means necessary for its eradication. Therefore, we created a chimeric between native Escherichia coli Tar chemotaxis receptor and human HB-EGF receptor so the bacterium may recognize diphtheria toxin. Moreover, we combined CheA and CheY in E. coli chemotaxis system with LuxAB and eYFP, respectively. When in contact, LuxAB and eYFP create resonance energy transfer system in which LuxAB gives its emission to eYFP. Without diphtheria toxin, CheA will be in phosphorylated state, allowing interaction with CheY and energy transfer, resulting in yellow color. Toxin binding into chimeric receptor will inhibit CheA phosphorylation, hindering interaction with CheY and energy transfer, resulting in blue color (i.e. LuxAB native color).</h5><br>
 
   <h3><b>Pathogenesis of Diphtheria: How Does Corynebacterium diphtheriae Cause the Disease?<b></h3>
 
   <h3><b>Pathogenesis of Diphtheria: How Does Corynebacterium diphtheriae Cause the Disease?<b></h3>
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   <h5>C. diphtheriae is a Gram-positive rod bacterium that causes diphtheria. It produces exotoxin with two fragments (AB toxin). Fragment B facilitates toxin internalization within host cell via endocytosis upon binding with HB-EGF receptor. Endosome internal environment allows catalytic process to split AB toxin into separate fragments, while fragment B forms a pore in endosome membrane, allowing fragment A to be transported into host cell cytoplasm. Fragment A then catalyzes modification of elongation factor 2 (EF-2), thereby attenuates protein synthesis and ultimately killing cell. This process underlies several complications found in patients with diphtheria, such as myocarditis, liver and kidney necrosis. In posterior pharynx, diphtheria infection leads to pseudomembrane formation, which is a local reaction and deposition of dead epithelial cells, bacteria, and immune cells enclosed within fibrin. Large formed pseudomembrane potentially causes respiratory tract obstruction and death.</h5>
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   <h5>C. diphtheriae is a Gram-positive rod bacterium that causes diphtheria. It produces exotoxin with two fragments (AB toxin). Fragment B facilitates toxin internalization within host cell via endocytosis upon binding with HB-EGF receptor. Endosome internal environment allows catalytic process to split AB toxin into separate fragments, while fragment B forms a pore in endosome membrane, allowing fragment A to be transported into host cell cytoplasm. Fragment A then catalyzes modification of elongation factor 2 (EF-2), thereby attenuates protein synthesis and ultimately killing cell. This process underlies several complications found in patients with diphtheria, such as myocarditis, liver and kidney necrosis. In posterior pharynx, diphtheria infection leads to pseudomembrane formation, which is a local reaction and deposition of dead epithelial cells, bacteria, and immune cells enclosed within fibrin. Large formed pseudomembrane potentially causes respiratory tract obstruction and death.</h5><br>
 
   <h3><b>Tar-mediated Chemotaxis System in Escherichia coli<b></h3>
 
   <h3><b>Tar-mediated Chemotaxis System in Escherichia coli<b></h3>
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   <h5>Chemotaxis system allows motile living cells to sensitize chemical signals in the environment and moving towards or away from them. This involves signal transduction processes mediated by ligand binding to chemoreceptor. In E. coli, chemotaxis mediated by methyl-accepting chemotaxis proteins (MCPs) has been widely studied. MCPs are transmembrane chemoreceptors with periplasmic ligand binding domain and cytoplasmic signaling domain. To date, four different E. coli MCPs have been identified: Tar, Tsr, Trg and Tap chemoreceptors.</h5>
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   <h5>Chemotaxis system allows motile living cells to sensitize chemical signals in the environment and moving towards or away from them. This involves signal transduction processes mediated by ligand binding to chemoreceptor. In E. coli, chemotaxis mediated by methyl-accepting chemotaxis proteins (MCPs) has been widely studied. MCPs are transmembrane chemoreceptors with periplasmic ligand binding domain and cytoplasmic signaling domain. To date, four different E. coli MCPs have been identified: Tar, Tsr, Trg and Tap chemoreceptors.</h5><br>
 
   <h5>Tar chemoreceptor mediates E. coli movement away from nickel and cobalt (repellent molecules), and towards aspartate and maltose (attractant molecules). Its cytoplasmic domain is associated with two proteins, CheW and CheA. CheW mediates signal transduction from Tar chemoreceptor to CheA, while CheA has a kinase domain which autophosphorylates its own histidyl residue. Tar chemoreceptor undergoes conformational change upon repellent molecule binding, leading to CheA activation and thus transfers its phosphoryl group to CheY, a regulatory protein that phosphorylates FliM in basal body of bacterial flagellum. These processes eventually lead the bacterium to swim smoothly away from repellent substance. On the other hand, attractant molecule binding into Tar chemoreceptor inhibits CheA and thus phosphorylation of CheY and FliM will not happen. This causes the bacterial flagellum to rotate in opposite direction and facilitates the bacterium to swim towards attractant substance.</h5>
 
   <h5>Tar chemoreceptor mediates E. coli movement away from nickel and cobalt (repellent molecules), and towards aspartate and maltose (attractant molecules). Its cytoplasmic domain is associated with two proteins, CheW and CheA. CheW mediates signal transduction from Tar chemoreceptor to CheA, while CheA has a kinase domain which autophosphorylates its own histidyl residue. Tar chemoreceptor undergoes conformational change upon repellent molecule binding, leading to CheA activation and thus transfers its phosphoryl group to CheY, a regulatory protein that phosphorylates FliM in basal body of bacterial flagellum. These processes eventually lead the bacterium to swim smoothly away from repellent substance. On the other hand, attractant molecule binding into Tar chemoreceptor inhibits CheA and thus phosphorylation of CheY and FliM will not happen. This causes the bacterial flagellum to rotate in opposite direction and facilitates the bacterium to swim towards attractant substance.</h5>
 
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Revision as of 15:19, 25 June 2018

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OVERVIEW
Diphtheria is becoming a prominent issue in Indonesia as its incidence is increasing recently. It also causes various complications, leading to morbidity and mortality. We realized the urgency of fast, reliable, and cheap early detection method for diphtheria infection as one of means necessary for its eradication. Therefore, we created a chimeric between native Escherichia coli Tar chemotaxis receptor and human HB-EGF receptor so the bacterium may recognize diphtheria toxin. Moreover, we combined CheA and CheY in E. coli chemotaxis system with LuxAB and eYFP, respectively. When in contact, LuxAB and eYFP create resonance energy transfer system in which LuxAB gives its emission to eYFP. Without diphtheria toxin, CheA will be in phosphorylated state, allowing interaction with CheY and energy transfer, resulting in yellow color. Toxin binding into chimeric receptor will inhibit CheA phosphorylation, hindering interaction with CheY and energy transfer, resulting in blue color (i.e. LuxAB native color).

Pathogenesis of Diphtheria: How Does Corynebacterium diphtheriae Cause the Disease?

C. diphtheriae is a Gram-positive rod bacterium that causes diphtheria. It produces exotoxin with two fragments (AB toxin). Fragment B facilitates toxin internalization within host cell via endocytosis upon binding with HB-EGF receptor. Endosome internal environment allows catalytic process to split AB toxin into separate fragments, while fragment B forms a pore in endosome membrane, allowing fragment A to be transported into host cell cytoplasm. Fragment A then catalyzes modification of elongation factor 2 (EF-2), thereby attenuates protein synthesis and ultimately killing cell. This process underlies several complications found in patients with diphtheria, such as myocarditis, liver and kidney necrosis. In posterior pharynx, diphtheria infection leads to pseudomembrane formation, which is a local reaction and deposition of dead epithelial cells, bacteria, and immune cells enclosed within fibrin. Large formed pseudomembrane potentially causes respiratory tract obstruction and death.

Tar-mediated Chemotaxis System in Escherichia coli

Chemotaxis system allows motile living cells to sensitize chemical signals in the environment and moving towards or away from them. This involves signal transduction processes mediated by ligand binding to chemoreceptor. In E. coli, chemotaxis mediated by methyl-accepting chemotaxis proteins (MCPs) has been widely studied. MCPs are transmembrane chemoreceptors with periplasmic ligand binding domain and cytoplasmic signaling domain. To date, four different E. coli MCPs have been identified: Tar, Tsr, Trg and Tap chemoreceptors.

Tar chemoreceptor mediates E. coli movement away from nickel and cobalt (repellent molecules), and towards aspartate and maltose (attractant molecules). Its cytoplasmic domain is associated with two proteins, CheW and CheA. CheW mediates signal transduction from Tar chemoreceptor to CheA, while CheA has a kinase domain which autophosphorylates its own histidyl residue. Tar chemoreceptor undergoes conformational change upon repellent molecule binding, leading to CheA activation and thus transfers its phosphoryl group to CheY, a regulatory protein that phosphorylates FliM in basal body of bacterial flagellum. These processes eventually lead the bacterium to swim smoothly away from repellent substance. On the other hand, attractant molecule binding into Tar chemoreceptor inhibits CheA and thus phosphorylation of CheY and FliM will not happen. This causes the bacterial flagellum to rotate in opposite direction and facilitates the bacterium to swim towards attractant substance.
Team UI Indonesia
igemui2018@gmail.com