Intellectual disability (ID) is a condition characterized by significant limitation in cognitive ability and adaptive behaviours with a disease onset before adulthood. ID affects 1-2% of children worldwide resulting in high social burden. Due to recent advance in high-throughput sequencing technology, genetic studies identified more than 2500 genes associated with ID, and autosomal-recessive ID counts more than 50 % of genetic causes of ID. Significant portion of ID cases shows anatomical abnormality in the brain such as microcephaly and lissencephaly, suggesting a neurodevelopmental origin of the disorder. However, little is known about the molecular mechanisms underlying ID, which limits possible interventions and therapeutics of the disease.
The goal of the project is to investigate the molecular mechanisms of ID using human-brain organoids. We have identified a group of ID-associated genes that encode proteins involved in RNA processing, and ID Patients with mutations in these genes have microcephaly.
In this project, the function of those genes on cortical development will be investigated with following specific aims.
Aim 1. To investigate the role of ID-associated genes in neural stem cell behaviour and neuronal migration and maturation in human cerebral organoid using electroporation mediated genetic manipulation
Aim 2. To determine transcriptomic changes upon genetic insults using single-cell RNA sequencing and identify target RNAs
Aim3. To identify the molecular mechanism of RNA processing involved in cortical development, and validate its functionality in cortical development
This project will enhance further understanding of human brain developmental process as well as discover novel disease mechanism of ID.
The student will obtain fundamental concepts of brain development including neural stem cell behaviour and neuronal maturation during human cortical development and neurodevelopmental disorders. Technically, the student will learn how to culture human stem cells and brain organoids and assess neural development using immunohistochemistry, imaging and computational analyses. Also the student will have opportunities to learn molecular biology for genetic manipulation of ID genes and biochemical approach to understand RNA process.
This project is advertised in relation to the research areas of MEDICAL SCIENCES. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.
NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM. Applicants are limited to applying for a maximum of 3 applications for funded projects. Any further applications received will be automatically withdrawn.
This project is funded by a University of Aberdeen Elphinstone Scholarship. An Elphinstone Scholarship covers the cost of tuition fees only, whether home, EU or overseas.
For details of fees: View Website
Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.