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Healthbots : Controlling Hyperglycemia

Healthbots : Controlling Hyperglycemia. Doug Tischer 5.8.08. Hyperglycemia. Acute Symptoms. Chronic Symptoms. Excessive hunger Excessive urination Excessive thirst Coma. Blindness Neuropathy – numbness of toes, feet, fingers Poor wound healing Hardening of blood vessels

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Healthbots : Controlling Hyperglycemia

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  1. Healthbots:Controlling Hyperglycemia Doug Tischer 5.8.08

  2. Hyperglycemia Acute Symptoms Chronic Symptoms • Excessive hunger • Excessive urination • Excessive thirst • Coma • Blindness • Neuropathy – numbness of toes, feet, fingers • Poor wound healing • Hardening of blood vessels • Kidney disease Normal blood glucose range: 300 – 400 uM http://www.medicinenet.com/diabetes_mellitus/page6.htm http://www.medicinenet.com/diabetes_mellitus/page7.htm#tocm

  3. The Solution • Add E. coli to the blood • Absorb excess glucose if above 400 uM • Chassis: Developed by UC Berekely 2007 iGEM project E. coli http://z.about.com/f/p/440/graphics/images/en/19192.jpg

  4. Abilities Survive for a long time (days) in the blood stream Does not replicate Consume glucose in excess of 400 uM

  5. Glucose Import:Phosphotransferase System (PTS)

  6. Important Genes, Proteins and Functions

  7. Modifications • Decrease EIIBCGlc – Mlc binding affinity • Mlc separates from EIIBCGlc at higher [glucose] • Mlc binds ptsG promoter • Reduced EIIBCGlc expression • Less glucose import • Enhance Mlc inhibition (currently about 18x) • Mutate Mlc DNA binding sites • Add more Mlc binding sites in promoter • Degradation tag on EIIBCGlc • Combats leakiness of (any) inhibitor

  8. Modifications Cont. • ptsG mRNA destabalization • sRNA SgrS binds the mRNA • Promoted by glucose-6-P or analog (α-GM-6-P) • Produce glucose analogs in vivo • Alpha-methyl-glucose

  9. Possible Projects Mutate EIIBCGlc binding site Mutate Mlc (protein) binding site Mutate promoter sequences/add more Mlc binding sites Degradation tag on EIIBCGlc – determine half life

  10. Possible Outcomes Total success: E. coli consume glucose as usual, but stop once extracellular glucose concentrations reach 400 uM. Partial success: E. coli stop consuming glucose at some point, just not at 400 uM. Interesting: Modulated glucose uptake.

  11. References Deutscher, J., Francke, C. and Postma, P.W. 2006. How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bactertia. Microbial and Molecular Biology Reviews. 2006: 939-1031

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