About the Project
Drug development has proven extremely challenging for complex brain disorders such as autism, schizophrenia and Alzheimer’s disease, leading many companies to scale back or abandon work on CNS conditions. A major contributing factor has been the high failure rate of compounds in late phase trials, which reflects our currently poor understanding of disease biology: failing compounds have been shown to perform the biological action for which they were designed, but this activity has no efficacy in…
treating disease. Genetic studies can provide invaluable insight into the genes and biological processes disrupted in disease, and it has been estimated that the selection of targets with strong genetic support could more than double success rates in drug development. In this project, the student will use genetic and bioinformatic analyses of molecular neuroscience data (primarily single cell transcriptomics) to address a key unsolved question: which brain regions, cell-types and molecular pathways are disrupted in genetically complex brain disorders, and how can we best utilise this information to prioritise potential novel therapeutic targets? The project builds upon existing work informed by the supervisors’ experience of performing drug target prioritisation for a multinational pharmaceutical company.
In carrying out this research, the student will be exposed to recent advances in molecular and cellular neuroscience and will gain experience in the processing and analysis of next-generation sequencing data, statistical genetics and relevant bioinformatic techniques. The student will work through a series of primary objectives:
- set up pipeline for the QC, processing and analysis of literaturederived scRNAseq datasets.
- apply this pipeline to transcriptomic data for the adult human brain, identifying region and cell-type specific patterns of gene expression.
- Interrogate the output from 2) using statistical genetic (common/rare variant association enrichment tests) and bioinformatic techniques (including structured Gene Ontology analyses) to identify regions, cell-types and molecular processes disrupted in brain disorders.
- Integrate disease-genetic and functional data to prioritise potential target genes for drug development. In working through the above objectives, the student will focus on schizophrenia, for which the genetic data is relatively well-powered. This will serve as training in the computational techniques and over-arching research methodology. Once complete, the student will have the freedom to steer the project in the direction that most interests them: interrogating genetic data for other conditions in order to perform a cross-disorder analysis; drawing upon scRNAseq datasets with a more detailed focus on specific cell-types (e.g. glia, blood-brain barrier) that are relevant to a disorder of particular interest to them; or expanding the analysis to look at neurodevelopmental cell-types.
Residency: GW4 BioMed3 studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but will be required to personally cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD. All studentships will be competitively awarded and there is a limit to the number of international students that we can accept into our programme (up to 30% cap across our partners per annum).
Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second-class degree will only be considered if they also have a master’s degree (at the University of Bath this must be at least a Merit). Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.
English requirements: If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. Please refer to the relevant university website for further information.
For informal enquiries, please contact GW4BioMed@cardiff.ac.uk
Funding Notes
These studentships are funded through GW4 BioMed3 MRC Doctoral Landscape Programme and consist of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£21, 805 p.a. for 2026/27, updated each year).
Additional research training and support funding of up to £5,000 per annum is also available
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