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Meningitis: The Smooth Criminal

Trevor Kraeger, Tyler Stokka, Jordan Williams, Chris Werner, Kassidy Branning, Anna Grim, Ben Weber, Emily Mytinger, Kaitlyn Rothamer, and GBH! SMART Team Project 2011. Meningitis: The Smooth Criminal. Common Cold or Something Worse???. Fever Persistent headaches Vomiting

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Meningitis: The Smooth Criminal

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  1. Trevor Kraeger, Tyler Stokka, Jordan Williams, Chris Werner, Kassidy Branning, Anna Grim, Ben Weber, Emily Mytinger, Kaitlyn Rothamer, and GBH! SMART Team Project 2011 Meningitis: The Smooth Criminal

  2. Common Cold or Something Worse??? Fever Persistent headaches Vomiting Stiff and painful neck Seizures Skin rash Dizzy spells

  3. Statistics of Meningitis 1,500 infected annually 900-3,000 reported cases annually Occurs in adolescents and young adults 1 out of every 7 adolescents will die Are you caught up on your vaccinations???

  4. What Exactly is Meningitis??? Swelling of the meninges Bacterial and viral Viral more common Bacterial is deadly  Outbreaks prevalent in close quarters Permanent effects

  5. Meningitis Across the Globe

  6. A Little Closer To Home

  7. Neisseria meningitidis Gram Negative bacteria Has an extra cell membrane Thinner peptidoglycan layer More complex (two zones rather than one)

  8. Gram Negative: Why it is important Evade and Invade

  9. How does this happen??? • Penetration of the blood brain barrier (BBB)… • …through the help of heparin, fibronectin and OpcA • Secret Agent Analogy

  10. another Heparin sulfate proteoglycan receptor method opca interactions with the heparin and fibronectin or vitronectin via pilius interactions, OpcA Three different ways to Get Into the Cell

  11. The 3 Major Proteins Key to Infiltration OpcA Heparin Fibronectin

  12. OpcA • “Arm” of bacterial Meningitis • Has a polar positive region in the notch on the “front” • Mainly consists of a Beta Barrel

  13. Heparin • A component of Blood serum • a highly-sulfated long unbranched polysaccharide • an anticoagulant Highest negative charge density of any known biological molecule!

  14. Fibronectin 2 Heparin Binding Sites Integrin Binding site!

  15. Meningitis Passing through Unnoticed • OpcA positive groove binds to negative Heparin • Heparin bind to positive fibronectin sites (two sites) • Fibronectin attaches to the integrin on the exterior of the blood-brain barrier • Receptor Mediated Endocytosis

  16. How to Prevent Meningitis from penetrating the BBB • Methods of prevention • OpcA positive groove • Nothing is successful yet • With the technology of today currently expanding it will only be a matter of time before a mechanism is found.

  17. S.M.A.R.T. Team Students Modeling A Research Topic

  18. Our Mission… • To perform background research on how meningitis works. • To model the proteins involved using JMOL • To give a kick butt presentation on meningitis and how it infiltrates the BBB! • After the above 3 objectives are completed, report back to GBH for your next assignment.

  19. Not as Easy as You Think

  20. Starting from Scratch

  21. X-ray Crystallography

  22. XYZ Data: Caterpillar to Butterfly

  23. Protein Data Bank Scientists make the protein data available to the public.

  24. Acknowledgments • Dr. Shannon Colton • MSOE/ Center for Biomolecular Modeling • SMART Team Program • Other Smart team groups at DCE

  25. Oh…btw… • …WE FOUND WALDO!!! • You probably didn’t notice him up there during the entire presentation, did ya???

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