Specific language impairment (SLI) is a neurodevelopmental disorder affecting up to 8% of pre-school children. SLI describes children who have problems with language development for no apparent reason, in contrast to language difficulties which are observed as a secondary manifestation of other conditions. If unresolved, SLI can have significant effects upon social, personal and educational development. SLI manifestation is highly heterogeneous and often (30-40% of cases) co-occurs with other neurodevelopmental disorders including dyslexia and attention deficit hyperactivity disorder (ADHD). Twin studies suggest that genetics plays an important role (~70%) in the aetiology of SLI, yet very few specific factors have been identified. Recently we identified very rare mutations in calcium/manganese transporter genes in children with language impairment. Calcium homeostasis is important for the regulation of many neuronal processes, including working memory, synaptic plasticity, and neuronal motility. Manganese dysregulation has been linked to neurodegenerative diseases including Parkinsonism and Alzheimer’s disease.
The aim of this project is to dissect the effects of these mutations on gene function to better understand the molecular mechanisms underlying brain development and language disorders. The candidate will use a multidisciplinary approach that combines human genetics, functional genomics, cell biology and biophysics. Different cellular model will be generated using CRISPR/Cas9 genome editing system. These models will then be characterised taking advantage of the outstanding imaging facilities available in St Andrews. We will study the effects of these mutations on ion homeostasis using electrophysiological approaches. In parallel, we will screen larger cohorts of children with language difficulties targeting ion transporters genes.
The ideal candidate will have an interest in neurodevelopmental disorders. While training will be provided, previous experience in human genetics and molecular biology is desirable.
For further details on the project and informal enquiries please contact to Dr. Silvia Paracchini ([Email Address Removed] ) with a CV and a covering letter.
This is a 3 year PhD studentship funded by the Cunningham Trust, comprising of tuition fees (Home/EU) and stipend at current research council rates