Overview

The CBM-Mentored Remote SMART Team Project in 3 Easy Steps

For the 2011-2012 CBM-Mentored Remote SMART Team project, teams will model proteins associated with the bubonic plague, or Black Death. This bacterial infection can be a serious life-threatening disease, and caused the deathof 1/3 of the population in Europe in the 14th century. SMART Teams will model proteins involved in how the causative agent, Yersinia pestis, facilitates enbubonicplaguetryinto the host.

Bubonic plague is characterized by swollen lymph nodes, the result of a bacterial invasion of the lymphatic sytem. The causative agent, Yersinia pestis, evades the host immune system by injecting toxins into immune cells, thus killing off the cells and inhibiting an immune response against the invading pathogen. Understanding how the bacteria infect the host immune system may help to further development of a vaccine or antibiotic that could prevent or treat the disease more effectively. (Image taken from http://en.wikipedia.org/wiki/File:Holbein-death.png)

Yersinia pestis targets the blood clotting pathway in order to facilitate entry into the host sytem. One of the virulency factors, Pla, is found on the surface of this bacterium. The pla, or plasminogen activator, protein increases the virulency of Yersinia pestis by a million-fold. Pla is a member of the omptin family and is a protease. We will focus on exploring the proteins that are necessary for the movement of the bacteria into the lymphatic system -- Pla and alpha2-antiplasmin.

The SMART Team program has three phases: the Qualification Phase, the Research and Design Phase and the Presentation Phase. During the Qualification Phase, the team learns about protein chemistry and Jmol. They then build a model of a protein and write an abstract to demonstrate proficiency in protein chemistry and Jmol. The Research and Design Phase challenges students to design a model and write an abstract of a particular protein of interest. The Presentation Phase allows students to put the Molecular Story together in a visual representation (poster/oral presentation) to showcase the project.

The CBM-Mentored SMART Team project will combine the Qualification Model and the Research and Design Model to tell a detailed Molecular Story in the Presentation Phase. The Qualification model is the surface protein, Pla, located on Yersinia pestis, which activates plasmin, which then cleaves fibrin, thus inhibiting clotting and enables the bacterium to gain entry into the host. The Research and Design protein is alpha2-antiplasmin, a protein that inhibits plasmin. Pla cleaves alpha2-antiplasmin, thus inhibting the inhibitor and increasing the concentration of active plasmin. Through these proteins, the CBM-Mentored Remote SMART Teams will have models to help tell the molecular story of bubonic plague and how the bacteria can invade the host.

We have designed the Remote SMART Team Modeling Project to have 3 Steps:

  1. Step 1 is to complete the Qualification Challenge, which asks the SMART Teams to design a model of Pla, the plasminogen activator. The target substrate of the Pla protein is plasminogen. Teams should model the amino acids on Pla that are needed to cleave plasminogen. Additionally, teams should write an abstract describing the molecular story of Pla and bubonic plague.
  2. Step 2 of the project is to design a model of alpha2-antiplasmin. Teams should also write an abstract describing how cleavage of antiplasmin facilitates inhibition of clot formation, thus facilitating the infection process.
  3. Step 3 is to put the Molecular Story of OpcA, heparin and fibronectin together to create a poster in which the role that Pla and alpha2-antiplasmin play in the infection process that leads to bubonic plague is explained. By combining what was learned in Steps 1 and 2, this Molecular Story can be translated into a poster to illustrate the story, using the physical models as accessories to tell this story.