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This project by the SMART Team dives into the complexities of meningitis, a serious condition with annual cases reported between 900-3,000, particularly in adolescents. We explore symptoms such as persistent headaches, neck stiffness, and more. Our research focuses on the structure and function of the Neisseria meningitidis bacteria that causes meningitis, how it penetrates the blood-brain barrier, and the proteins involved in this process. We aim to raise awareness about vaccinations and prevention measures through detailed research and modeling.
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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 Stiff and painful neck Seizures Skin rash Dizzy spells
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???
What Exactly is Meningitis??? Swelling of the meninges Bacterial and viral Viral more common Bacterial is deadly Outbreaks prevalent in close quarters Permanent effects
Neisseria meningitidis Gram Negative bacteria Has an extra cell membrane Thinner peptidoglycan layer More complex (two zones rather than one)
Gram Negative: Why it is important Evade and Invade
How does this happen??? • Penetration of the blood brain barrier (BBB)… • …through the help of heparin, fibronectin and OpcA • Secret Agent Analogy
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
The 3 Major Proteins Key to Infiltration OpcA Heparin Fibronectin
OpcA • “Arm” of bacterial Meningitis • Has a polar positive region in the notch on the “front” • Mainly consists of a Beta Barrel
Heparin • A component of Blood serum • a highly-sulfated long unbranched polysaccharide • an anticoagulant Highest negative charge density of any known biological molecule!
Fibronectin 2 Heparin Binding Sites Integrin Binding site!
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
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.
S.M.A.R.T. Team Students Modeling A Research Topic
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.
Protein Data Bank Scientists make the protein data available to the public.
Acknowledgments • Dr. Shannon Colton • MSOE/ Center for Biomolecular Modeling • SMART Team Program • Other Smart team groups at DCE
Oh…btw… • …WE FOUND WALDO!!! • You probably didn’t notice him up there during the entire presentation, did ya???