PhD Studentship Nanoparticle exposure of placental barriers – an indirect route of teratogenesis?



This is a 3-year PhD studentship funded by the Marie Curie Initial Training Networks (ITN). It is based in Bristol but with two secondments each of 3 months to University College Dublin and to Industry.

Supervisors: Dr. Patrick Case, University of Bristol and Prof. Kenneth Dawson, University College Dublin.

Until now it has been assumed that teratogens will damage a baby directly, by passing from the maternal blood, through the placenta and into the foetal circulation. We have discovered that this may not necessarily be so. In two papers published in Nature Nanotechnology we have demonstrated an indirect mechanism. In these experiments an established model barrier of the human placenta, a bilayered cell barrier of BeWo cells, a choriocarcinoma cell line, was grown on transwell inserts. The cell barrier was exposed to CoCr nanoparticles, metal ions, altered oxygen or drugs that initiate mitochondrial free radicals. This exposure set up a process of cell to cell signalling through connexin and pannexin channels within the cell barrier. This in turn stimulated a release of factors that caused DNA damage and chromosome aberrations in human fibroblasts or stem cells on the other side and also led to a secretion of cytokines and chemokines. Importantly the nanoparticles, ions or drugs did not pass through the barrier.

We now wish to focus on two key aspects of this research. Firstly we wish to improve the cell barrier to make it a more faithful replica of the actual placenta. To do this we will isolate primary trophoblasts from human placenta and use them to make bilayered and monolayered barriers with and without syncytialisation. Up until now this has not been possible due to the lack of cell division of these primary cells. However using novel technology we have recently succeeded in creating primary trophoblast confluent cell barriers on transwell inserts and wish to extend this work.

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A second feature of this research will be to explore the mechanism and actions of the signalling. Taking DNA damage chromosomal aberrations and cytokine secretion as our endpoints, we will explore the role of connexins, pannexins and purinergic transmission in the primary cell barrier signalling. We will explore different functionalities of nanoparticles, whether coated with different protein coronas or with select modifications to their surface chemistry. This programme of work will explore the risks of nanoparticle exposure to a foetus, but more critically will examine the mechanism by which the risk might be incurred.

Candidate Requirements:

Applicants should hold or be about to achieve a First or Upper-Second (2.i) class degree in a relevant subject.

Funding:

Marie Curie Studentships are available to all EU students including UK nationals. The studentship is available for 3 years and the successful candidate will receive a stipend of at least £13,726 per annum. Fees will be met in full. The start-date is September/October 2013 (negotiable).

How to Apply:

Applications should be made using the University of Bristol online application form at:

http://www.bristol.ac.uk/pg-howtoapply

In the Programme Choice section, please select ‘Faculty of Medicine and Dentistry’ and ‘PhD Surgery’ and insert the project title in the Research Details section. 

The closing date for this studentship is 8th July 2013.

Contacts:

For further details please contact Dr. Patrick Case ([email protected]).

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