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This research topic focuses on understanding the molecular world through the analysis of the bubonic plague's Pla protein. The Pla protein plays a crucial role in the spread and virulence of the bubonic plague.
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The Bubonic Plague's Pla Protein Ben Weber, Kaitlyn Rothamer, Hailey Nuthals, Alex Esselman (Dr. Colton and MSOE)
SMART Team Students Modeling A Research Topic Purposes: • To understand the molecular world through the application of science in analyzing facts • Modeling proteins to understand the implications of their structural formulas
2011-12 Topic The Bubonic Plague's Pla protein
The Bubonic Plague "The Black Death" First occurred in the Byzantine Empire (500 AD), where it killed about 25 million people Next hit Europe in the 1330's, killing nearly 1/3 of the population. Spread from flea bites that jumped rides on trade ships from China to Italian ports Caused by bacteria Yersinia Pestis
Symptoms Characterized by swollen lymph nodes, fever, vomiting of blood, gangrene on fingers Death within 2-7 days.
In Today's Terms Only 10-30 cases of the plague are reported each year in the U.S. Globally, about 1,000-3,000 cases each year
Biological Warfare Earliest use of biological warfare - Chinese warriors would launch dead bodies infected with plague using catapults Infected and killed enemies rapidly Today... Could be used as a terrorism weapon - quickly causes epidemic If made to be drug resistant, could be even more horrible
Gram Negative Bacteria Y. Pestis is a gram negative bacteria Gram negative: bacteria that are not affected by crystal violet dye in Gram staining protocol. Used to classify bacteria based on their cell walls Gram negative bacteria are known to cause swelling Affects lipopolysaccharide layer (LPS)
Where the Problem Starts: Clotting Clotting is what the body uses to isolate bacteria Once clotted, white blood cells can take down bacteria Clots consist of fibrin • Pla prevents clotting (problem begins)
Cleaving Antiplasmin Cleaver: electrically excited water molecule Pla's cleaver cleaves active arm in antiplasmin & bond site in plasminogen Leads to more plasmin in blood. Antiplasmin attracts plasmin, pulls it out of shape Maintains healthy levels of plasmin Works to keep fibrin intact Intact fibrin = regular clotting process. Keep in mind - since Y. pestis is transferred through flea bites, blood tries to clot to kill it...
Putting it Together Pla's cleaver increases plasmin More plasmin means less fibrin Less fibrin means less ability to clot If there are no clots, Y. pestis is free to travel the human body
How it Kills Y. pestis begins to attack the lymphatic system (bubonic plague) Can spread to respiratory system (called pneumonic plague) Can also affect blood system (called septicemic plague)
Sneaky Bacteria Y. pestis creates F1 & V antigens which prevent its absorption into cells Hides in white blood cells and lymph nodes to avoid detection from neutrophils Neutrophils trap and kill microbes existing outside of white blood cells < F1 antigen V antigen >
Immunizations No specific, tell-all immunization has been found... Possibilities: Vaccine made to target F1 and V antigens This way the plague can't hide Problem: many newer strains of Y. pestis are drug resistant with altered antigens
When All Goes Wrong Without immediate treatment, the plague can spread and kill quickly Plague has possible mutations to resist antibiotics Unless we understand how this plague works, a second, more fatal form could spread
Practical Uses Though a problem in plagues, the cleaving reaction could be used for good instead of evil: Cleaning oil spills Better soaps Cancer treatment/other medicines
Bibliography http://cbm.msoe.edu/stupro/smart/remote/step1.html http://en.wikipedia.org/wiki/File:Black_Death.jpg http://www.themiddleages.net/plague.html http://alchemipedia.blogspot.com/2009/09/black-death-bubonic-plague-spread-in.html http://en.wikipedia.org/wiki/File:Acral_gangrene_due_to_plague.jpg http://en.wikipedia.org/wiki/Black_Death#Symptoms http://www.scifibloggers.com/top-10-diseases-worst-killers-in-history/ http://members.tripod.com/miss_hand_history/warminster/alistair.htm https://encrypted-tbn2.google.com/images?q=tbn:ANd9GcRR649XpPnjB0BrMrOTt1oWc7hFgEeAxiFu9H62Td5cvcfy1cMJ http://www.medicinenet.com/plague/article.htm http://image.shutterstock.com/display_pic_with_logo/154111/154111,1222961184,8/stock-photo-this-is-a-d-representation-of-the-yersinia-pestis-bacteria-better-known-as-the-bubonic-plague-18274534.jpg http://www.visualphotos.com/photo/1x6040300/yersinia_pestis_bubonic_plague_bacteria_sem_b2201334.jpg http://newsimg.bbc.co.uk/media/images/45390000/jpg/_45390167_002877261-1.jpg http://www.bioinformaticonline.com/images/topics/pdb1.png http://en.wikipedia.org/wiki/Gram-negative_bacteria http://en.wikipedia.org/wiki/File:Gram_negative_cell_wall.svg http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Clotting.html https://encrypted-tbn3.google.com/images?q=tbn:ANd9GcTGVOZ9dKPh9WII-miKkwK4RaO-BwUiBY3rW4xAFrRc_ebPE9k4Jg https://encrypted-tbn0.google.com/images?q=tbn:ANd9GcQO8cB5XrZ9ti9D2M47R1TGQEORuKbV3_FNe6wwHwwmJsI-jHuPVw http://www.sigmaaldrich.com/img/assets/27040/fibrinogen-cleave.jpg http://chemwiki.ucdavis.edu/@api/deki/files/10161/=image132.png http://www.nostatic.com/proteins/Plasmin/plasmin.gif http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001622/ http://www.wisegeek.com/what-are-neutrophils.htm https://docs.google.com/presentation/d/1WH1stY5CsIrWUR77WzP5l8cTB0qpEifdRavuqbD2RE4/edit#slide=id.g114cf187_2_0 http://upload.wikimedia.org/wikipedia/commons/thumb/0/00/Aspartyl_protease_mechanism.png/800px-Aspartyl_protease_mechanism.png http://www.dynamicscience.com.au/tester/solutions/war/biological/biologicalwrf.htm http://www.textmed.com/heatmaps/disease/bubonic-plague-us-heatmap.gif http://bioch.szote.u-szeged.hu/astrojan/protein/pictures/atpazf1a.gif http://mcl1.ncifcrf.gov/waugh_lcrv.html http://www.burdr.com/wp-content/uploads/2010/05/oil-spill-gulf-of-mexico-from-deepwater-horizon.jpg http://beeyondthehive.com/store/media/thumbnails/HoneySoap
Tools Protein Data Bank
(Tools ctd.) Jmol Jmol Java program used to view and enhance understanding of molecular models Able to shape and control model
Acknowledgements Dr. Colton (MSOE SMART team program) MSOE Center for Biomolecular Modeling Mr. Heeren (Local SMART team leader)