EASTBIO: Investigating the 16p11.2 genetic autism risk factor in brain development. at University of Edinburgh on FindAPhD.com

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Dr Thomas Pratt, Prof D Price No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

Deanery of Biomedical Sciences

Autism spectrum condition or ‘autism’ is associated with numerous genetic risk factors including the polygenic 16p11.2 microdeletion. Patients heterozygous for the 16p11.2 microdeletion (16p11.2^+/-) account for about 1% of autism cases making it one of the most common genetic causes of autism. A central question is what neural cells are affected and how their cell and molecular biology is perturbed to predispose the brain to developing autism.

The proper functioning of the mature cerebral cortex depends on the balance between excitatory neurons (originating from progenitors located in the ventricular zone of the cerebral cortex) and inhibitory interneurons (originating from progenitors located in the ganglionic eminences) that migrate to the cortex. This Excitatory/Inhibitory (E/I) balance is important for normal brain function and disruption to the E/I balance is hypothesised to underpin autism. The onset of autism in infancy suggests the hypothesis that genetic risk factors act during pre-natal brain development and we have used bioinformatic analysis to identify cells in developing human forebrain that are vulnerable to the 16p11.2 microdeletion (Morson et al., 2021, Yang et al BioRxiv).

This project will investigate 16p11.2 microdeletion cell and molecular phenotypes, specifically those affecting the E/I balance, during brain development. The project will employ human induced pluripotent stem cell (hIPSC) derived 16p11.2^+/- neurons and/or a complementary 16p11.2^+/- rat model. Techniques will include a combination of hIPSC neural differentiation, RNA sequencing, bioinformatic analysis, immunohistochemistry, and in situ hybridisation.

Funding Notes

Application Procedure
Download application and reference forms from http://www.eastscotbiodtp.ac.uk/how-apply-0
Completed application form along with your supporting documents should be sent to our PGR student team at [Email Address Removed] by 16 December 2021. Unfortunately due to workload constraints, we cannot consider incomplete applications.
References: Please send the reference request form to two referees. Completed references for this project should also be returned to [Email Address Removed] by the closing date: 16 December 2021.
It is your responsibility to ensure that references are provided by the specified deadline.

References

Sarah Morson, Yifei Yang, David J Price, Thomas Pratt (2021) Expression of Genes in the 16p11.2 Locus during Development of the Human Fetal Cerebral Cortex. Cerebral Cortex, https://doi.org/10.1093/cercor/bhab067
Yifei Yang, Sam A. Booker, James M. Clegg, Idoia Quintana Urzainqui, Anna Sumera Zrinko Kozic, Owen Dando, Sandra Martin Lorenzo, Yann Herault, Peter C. Kind, David J. Price, Thomas Pratt. Identifying developing interneurons as a potential target for multiple genetic autism risk factors in human and rodent forebrain. bioRxiv 2021.06.03.446920; doi: https://doi.org/10.1101/2021.06.03.446920

Where will I study?

University of Edinburgh

One of the world''s top universities, consistently ranked in the world top 50 and placed 20th in the QS World University Rankings 2020. We provide a stimulating working, learning and teaching environment with access to excellent facilities and attract the world''s best, from Nobel Prize winning laureates to future explorers, pioneers and inventors.

EASTBIO: Investigating the 16p11.2 genetic autism risk factor in brain development.

University of Edinburgh College of Medicine and Veterinary Medicine