Team:The Citadel-Charleston/ProjectPYY

Overview    Peptide YY   Population Control

Overview of the Protein

     PYY3-36 is an endogenous hormone of the ileum and colon, postprandially released in proportion to the calories consumed during a meal.  The peptide can be absorbed into the circulatory system and pass the blood-brain barrier, where it acts as a primary contributor to energy homeostasis.  By exerting agonist action on the NPY Y2-receptor in the arcuate nucleus of the hypothalamus,  PYY3-36 causes an inhibition of gastric motility and a substantial reduction in appetite.

     PYY3-36 has received considerable research attention in Homo sapiens and in various rodent species.  The effects of supplementation to a subject's natural PYY3-36 levels with additional peptide have been well characterized.  Studies attempting to discover a variation in the amount of PYY3-36 produced by obese persons to that produced by a lean person have been inconclusive, but its anorectic effect remains unchallenged.  PYY3-36's ability to reduce appetite in persons of all body types is widely accepted within the scientific community.  The peptide has therefore been identified for potential usage in the treatment of obesity and appetite dysfunction.

     In one example study, human subjects were given an infusion of either PYY3-36 (2 nmol / m2 body-surface area) or saline solution.  After two hours had elapsed, all subjects were offered a buffet meal capable of satisfying any appetite.  Consumption rates were strictly measured, and it was shown that the caloric intake of individuals who had received the PYY3-36 infusion ate 30% less on average than subjects who received the saline infusion.  The results of this study were consistent irrespective of a subject's body type.   Lean or obese, subjects universally displayed a marked decrease in appetite.

PYY 3-36 at The Citadel

     The goal of The Citadel iGEM team was to construct a RFC10-complaint Biobrick part that encoded the protein PYY3-36 and could be successfully integrated into genetic circuits in the chassis E.coli.  Furthermore, we hoped to show that, with Biobrick protein coding sequences such as PYY3-36, systems could be designed for E.coli (or other chassis native to the intestinal microbiome) that would have application potential as novel, safe, and potent means for influencing neurological processes such as appetite from across the brain-gut axis.

PYY 3-36 BioBrick Parts

1. PYY3-36
2. PYY3-36 in expression cassette
3. PYY3-36 in autotransporter

References

1. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR (September 2003). "Inhibition of food intake in obese subjects by peptide YY3-36". The New England Journal of Medicine 349 (10): 941–8.
2. Nonaka N, Shioda S, Niehoff ML, Banks WA (September 2003). "Characterization of Blood-Brain Barrier Permeability to PYY3-36 in the Mouse." The American Society for Pharmacology and Experimental Therapeutics 306 (3):948-53.
3. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR (August 2002) “Gut hormone PYY3-36 physiologically inhibits food intake.” Nature 418: 650-4.
4. Halatchev IG, Cone RD (March 2005) “Peripheral administration of PYY3–36 produces conditioned taste aversion in mice” Cell Metabolism 1 (3): 159-68.