The neocortex is a highly specialized structure involved in higher-order brain functions such as sensory, motor, and cognitive processes. Throughout evolution, the neocortex of primates has increased enormously in size and complexity, which has given humans remarkable cognitive and intellectual abilities such as abstract thinking and creativity. Understanding human cortical development is crucial not only to obtain evolutionary insights into cortical development but also to uncover the underlying aetiology of human-specific diseases such as neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Despite the clinical importance of neocortical development, our understanding of the molecular mechanisms behind neocortical expansion remains largely unknown.
Precise control of when neural stem cells divide and what cell type they generate after division is critical for human cortical development. The developing human cortex has a distinctive population of neural stem cells called outer radial glial cells (oRGCs) that animal models such as mouse do not have. oRGCs are responsible for the expansion of the human brain as they generate neurons in the superficial layers of the neocortex. Therefore, it is important to understand how oRGCs are generated and behave during cortical development. In this PhD studentship, you will investigate the molecular mechanisms that instruct the generation of oRGCs and thus drive cortical expansion.
To study human cortical development, it is essential to use a human brain model system, given that rodent models do not mimic the cellular structure and developmental process of the expanded human cortex. However, because of limited access to human brain tissue and ethical concerns, it has been difficult to directly study human cortical development. In vitro model systems composed of human cells have emerged as an invaluable tool for modelling human-specific development and diseases. Human brain organoids are 3D self-assembled aggregates of brain cells derived from induced pluripotent stem cells, which recapitulate the complex structure of the developing human brain including cellular diversity and organization, and molecular signatures of the various stages of development. Therefore, human brain organoids provide a unique opportunity to model developmental and pathological processes not accessible with alternative approaches. Using this model system, you will investigate the functional importance of transcriptional regulators in controlling fate specification of neural stem cells with a particular focus on the generation of oRGCs. To address this aim, you will harness a CRISPR-mediated genetic manipulation tool to systematically knockout genes of interest. Combined with bioinformatic analyses from single-cell RNA sequencing data and functional study from the brain organoids, you will determine the functional importance of key target genes in human cortical development.
During this studentship, you will gain an in-depth understanding of fundamental concepts in brain development, including neural stem cell behaviour, human cortical development, and neurodevelopmental disorders. The project will provide training in state-of-the-art experimental techniques, including stem cell culture, brain organoids, perturbing cells genetically using CRISPR, immunohistochemistry and high resolution imaging. The bioinformatics side of the project will allow you to develop valuable computational skills in a supportive and highly interdisciplinary collaboration.
APPLICATION PROCEDURE:
Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
You should apply for the Degree of Doctor of Philosophy in Medical sciences to ensure your application is passed to the correct team
Please clearly note the name of the supervisor and exact project title on the application form. If you do not mention the project title and the supervisor on your application, then it will not be considered for the studentship.
Candidates must have a strong background in Biomedical sciences and have at least an Upper Second Class Honours degree (or equivalent) in a relevant subject.
Admissions enquiries can be made to [Email Address Removed]
For further information on the project particulars, please contact Dr Eunchai Kang [Email Address Removed]
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