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Maternal immune activation: advancing from rodents to humans through a development of a hIPSC model to study gene x environment interactions


Project Description

Human induced pluripotent stem cells (hiPSCs) present a unique opportunity to reduce animal use in studying the aetiology of neurodevelopmental disorders (NDD). Their capacity to differentiate into multiple different tissue types allows researchers to observe tissue formation and function under normal conditions, but also under the influence of disease-causing agents. However, only genetic drivers of disease have been studied in hiPSC. Importantly, beside genetics, various environmental factors also increase risk for NDD, particularly if the exposure occurs during critical periods of fetal brain development. If hiPSC are to deliver on their potential, the challenge is to use them to study not only genetic, but also environmental disease risk factors opening the door to studying gene x environment interactions.

In this context, epidemiology and animal models provide evidence for a link between maternal immune activation (MIA) during pregnancy and increased risk for psychiatric neurodevelopmental disorders, including autism and schizophrenia in the affected offspring. There is, however, a pressing need to translate these findings into human model systems, due to differences in the development of human and animal brains, both in terms of gene regulatory networks and cellular proliferative behaviour. This studentship will develop a model of MIA using hiPSC to enable: (1) elucidation of causal cellular and molecular mechanisms driving the adverse effects of MIA on human fetal brain development; (2) establish the relevance of the animal data for human health and disease and (3) greatly broaden the potential of hIPSCs in disease modelling, leading to a significant reduction in the number of rodents and non-human primates used in these models.

For further details of this project please refer to the NC3Rs website using the link below:

https://www.nc3rs.org.uk/maternal-immune-activation-advancing-rodents-humans-through-development-hipsc-model-study-gene-x

Start date: 1st June 2019

For more information on how to apply, please visit the IoPPN website: https://www.kcl.ac.uk/ioppn/study/prospective-students/programmes-of-study/pgr/fundedresearchopportunities/acv-nc3rs-2019.aspx

Funding Notes

Funding provides full support for tuition fees for the three-year duration of the studentship, associated project costs, and an annual tax-free stipend. In line with the MRC, NC3Rs sets a higher minimum stipend level for inside London – for 2018/19 this is £16,777.

For more information on eligibility, please see the NC3Rs website at: View Website

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