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SoCoBio (Universities of Southampton, Kent, Sussex, Portsmouth and NIAB EMR)

Modelling drug and ion transfer through trans-syncytial nanopores

Primary Supervisor: Dr Bram Sengers (Bioengineering Research group, School of Engineering, University of Southampton)

Co-Supervisors:
Professor Rohan Lewis (Faculty of Medicine, University of Southampton)
Dr Anthony Lewis (School of Pharmacy & Biological Sciences, University of Portsmouth)

Project Summary

Rationale:
How pharmaceuticals and environmental toxins cross the placenta is not clear and this has a direct impact on drug safety.

There is physiological evidence for a diffusive pathway across the placenta, but no anatomical route has been previously demonstrated.

Recently we performed the first three-dimensional ultrastructural analysis of the human placental barrier. This analysis revealed novel trans-syncytial nanopores directly connecting the maternal and fetal sides of the placental barrier (Figure 1 above: 3D image based computational model of solute transport through a placental nanopore, showing the gradient between the high maternal (red) and low fetal concentrations (blue). ). Computational modelling of diffusion through these complex trans-syncytial nanopores can estimate their permeability.

Many drugs are charged and the physiological significance of these nanopores will critically depend on the pore density, molecular size and electrochemical gradients.

The aim of this project is to establish the role of nanopores in placental transfer in a quantitative manner, using a fully integrated experimental and computational modelling approach.