(MRC DTP) Using neuroimaging to understand brain development in syndromic autism spectrum conditions
About the Project
Children with rare conditions are 30 times more likely than the general population to be diagnosed with intellectual disability, autism and ADHD. Currently, there are no effective treatments/therapies for these difficulties which have a significant impact on quality of life. A major challenge has been the lack of understanding of how genetic mutations impact brain development and how this, in turn, may relate to learning difficulties. The current research proposal uses the single-gene condition Neurofibromatosis 1 (NF1) as a model to better understand the effect of the NF1 pathogenic variants on the brain. Approximately 70% of individuals with NF1 have co-occurring learning problems, 50% have ADHD, and 30% autism. Understanding the effect of the NF1 genetic variation on brain development will help us gain insight into how these differences may relate to learning and behavioural difficulties. This project will use advanced neuroimaging techniques including MR Spectroscopy and imaging transcriptomics to interrogate the large repository of structural and functional MRI brain scans in NF1. In particular, the project has the following aims:
(i) to examine how anatomical brain differences (such as cortical thickness, brain volumes etc) between NF1 versus neurotypical controls relate to the spatial pattern of autism risk gene expression, and
(ii) to examine how the GABA receptors genes expression profiles in the frontal lobe in NF1 relates to the neurotransmitter estimates obtained from MR Spectroscopy.
The project will be embedded within wider projects funded by US Department of Defense Synergistic Grant award and NIHR Biomedical Research Centre award to the supervisory team and will benefit from access to administrative support and funding. The student will receive training in the analyses of imaging transcriptomics data, MR Spectroscopy and will participate in the collection of new neuroimaging datasets. There is expertise within the supervisory team in psychiatry, cognitive neuroscience, MR Spectroscopy and computational modelling of large datasets. The supervisory team have a track record of scanning children with neurodevelopmental conditions.
Eligibility
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – on the application form you must select MRC DTP PhD Programme. If you select the incorrect programme your application cannot be considered. Full details on how to apply can be found on the MRC DTP website.
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application, please contact our admissions team.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website.
Funding Notes
Studentship funding is for 4 years and covers tuition fees and an annual stipend. This does not include any costs associated with relocation.
References
Sawyer C, Green J, Lim B, Pobric G, Jung J, Vassallo G,.. & Garg,S. Neuroanatomical correlates of working memory performance in Neurofibromatosis 1. Cereb Cortex Commun. 2022;3(2):tgac021.
Garg S, Williams S, Jung J, Pobric G, Nandi T, Lim B, Vassallo G, Green J, Evans DG, Staff CJ, Parkes, L, Stivaros S. Non-invasive brain stimulation modulates GABAergic activity in Neurofibromatosis 1. 2021, https://doi.org/10.21203/rs.3.rs-885650/v1
Lea-Carnall CA, Williams SR, Sanaei-Nezhad F, Trujillo-Barreto NJ, Montemurro MA, El-Deredy W, & Parkes LM (2020). GABA modulates frequency-dependent plasticity in humans. iScience, 23(11).
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