Team:British Columbia/Modeling2

UBC iGEM 2015

 

Modeling

 

Modeling accumulative imidacloprid toxicity in A. mellifera

We are basing our chronic exposure toxicity model on the fact that imidacloprid binds irreversibly to acetylcholine receptors in the nervous system, and as such display patterns of accumulative toxicity over time. As such, the lethal time-to-effect relationship can be expressed as LT50∝DtP where:

  • LT50 = time when half the insects succumb to toxin
  • D = dose of toxin per unit time
  • P = power law exponent

Our determination of the toxicity threshold is derived from Haber’s rule C x t = k where

  • C = concentration of gas
  • t = time necessary to inhale gas to produce toxic effect
  • k = constant, dependent on gas itself and toxic effect

However, one caveat in the use of Haber’s rule is in that it applies to inhalation only, but imidacloprid ingestion in A. mellifera can occur through inhalation (direct dust exposure) or oral ingestion of droplets, nectar, or pollen from treated plants.

As such, we have used the toxicokinetic-toxicodynamic model proposed by Rondeau et al. IMAGEGOESHERE where

  • D(t) = either a single initial dose or a continuous, lower, chronic dose
  • C = change in total-body toxic load
  • τM = metabolic decay time
  • CB = amount of bound toxin
  • τD = time constant for dissociation

CB, the amount of bound toxin, can be determined by IMAGEGOESHERE where

  • C = change in total-body toxic load
  • CB = amount of bound toxin
  • τA = time constant for receptor binding
  • τD = time constant for dissociation

Rondeau et al. also suggest that IMAGEGOESHERE where

  • E(t) = cumulative damaging biological effect

Using an arbitrary threshold for E(t) (e.g. 1 = LT50), we are able to determine cumulative toxicity both without imidacloprid (thick blue line), with imidacloprid (dashed red line), and with imidacloprid and our genetically engineered Gilliamella (dashed blue line).

IMAGEGOESHERE

For the generation of our cumulative toxicity graphs, we used literature values of 6-CNA decay (time constant = 10 hours), as well as known concentrations of bee gut flora (107 bacteria, of which Gilliamella makes up 12%), bee gut volume (1mm x 1mm x 1cm).

We then conducted sensitivity analysis, determining the range of a) the imidacloprid decay constant, b) the concentration of bacteria in the gut, and c) the concentration of imidacloprid needed to alter bee survival time (as defined by our threshold of 1 = LT50).

IMAGEGOESHERE