Back to search results

PhD Studentship: Statistical inference of cell type specific epigenetic profiles for the molecular epidemiology of brain disorders. MRC GW4 BioMed DTP PhD studentship 2023/24 Entry, PhD in Medical Studies

University of Exeter

Qualification Type: PhD
Location: Exeter
Funding for: UK Students, EU Students, International Students
Funding amount: From £17,688 UK tuition fees, as well as a Stipend matching UK Research Council National per annum
Hours: Full Time
Placed On: 20th September 2022
Closes: 2nd November 2022
Reference: 4520

The focus of this data science PhD project is understanding which neural cell types are affected by the genetic and epigenetic variation associated with brain disorders. Genome-wide association studies (GWAS) have facilitated the identification of thousands of genetic variants associated with neurodegenerative and neurodevelopmental disorders. However, for the vast majority of genetic associations it is unclear how, and in what cell-type, they exert their effect. A fundamental conclusion is that many genetic risk factors mediate their effects by influencing the regulation of gene expression. As a consequence, there is a need to generate epigenomic profiles to annotate gene regulatory states across the genome in individual cell types. Such profiling across a range of brain cell types is both time-consuming and expensive, prohibiting analysis at scale. Yet, there is an abundance of data from profiling of bulk brain tissue where gene regulatory state is surveyed across the population of cell types.

This project will assess the extent to which we can use innovative mathematical methodologies to infer the constituent cell-level epigenomic profiles from these existing data profiled from bulk brain tissue. The proposed project consists of 3 objectives designed to provide the student with experience of a range of bioinformatics tools and genomic data types. Critically, we have matched epigenetic data from prefrontal cortex and three constituent neural cell types from the same individual permitting characterisation of the accuracy of the described computational methods. We have epigenomic data available from a range of experiments (DNA (hydroxy)methylation, ATAC-Seq, ChIP-Seq) and technologies (microarray, Illumina short read, Oxford Nanopore long read sequencing, 10x single cell RNA-Seq and ATAC-Seq), which the student can choose to incorporate into their project in order to tailor their research experience to their own personal objectives. In addition, the student would be expected to take ownership of the specific phenotype(s) we prioritise and identify the datasets for analysis. Specific objectives:

  1. Characterise the cell specificity of epigenomic features detected from heterogeneous brain tissue. The student will use reference cell-specific profiles to reconstruct brain level profiles which will be compared to empirical profiles from bulk brain tissue enabling us determine to what extent bulk level profiles are a linear combination of existing cell level profiles. We can then deduce annotations for cell types not yet profiled, and provide a comprehensive map of gene regulatory states in all brain cell types. This will form the basic of GWAS enrichment analyses using methods such as LD score regression.
  2. Perform a cell-specific association analysis using epigenomic data generated from brain tissue. Taking a methodology developed for deconvoluting whole blood profiles, tensor composition analysis will be applied to epigenetic data generated from heterogeneous brain tissue to obtain genome-wide data profiles for neurons, oligodendrocytes and microglia. After validating the performance of this method, an epigenome-wide association analysis will be performed for a brain disorder of the student’s choosing. We have data for schizophrenia, autism and Alzheimer’s disease, but there exist data in public repositories on alternative disorders.
  3. Perform a cell type specific genetic analysis of epigenomic variation using epigenomic data generated from brain tissue. The student will generate a catalogue of neural cell-type specific epigenetic quantitative trait loci in large sample cohorts by incorporating an interaction between cellular abundance and genotype in the quantitative trait loci analysis framework.
We value your feedback on the quality of our adverts. If you have a comment to make about the overall quality of this advert, or its categorisation then please send us your feedback
Advert information

Type / Role:

Subject Area(s):

Location(s):

PhD tools
 

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Ok Ok

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Manage your job alerts Manage your job alerts

Account Verification Missing

In order to create multiple job alerts, you must first verify your email address to complete your account creation

Request verification email Request verification email

jobs.ac.uk Account Required

In order to create multiple alerts, you must create a jobs.ac.uk jobseeker account

Create Account Create Account

Alert Creation Failed

Unfortunately, your account is currently blocked. Please login to unblock your account.

Email Address Blocked

We received a delivery failure message when attempting to send you an email and therefore your email address has been blocked. You will not receive job alerts until your email address is unblocked. To do so, please choose from one of the two options below.

Max Alerts Reached

A maximum of 5 Job Alerts can be created against your account. Please remove an existing alert in order to create this new Job Alert

Manage your job alerts Manage your job alerts

Creation Failed

Unfortunately, your alert was not created at this time. Please try again.

Ok Ok

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

 
 
 
More PhDs from University of Exeter

Show all PhDs for this organisation …

More PhDs like this
Join in and follow us

Browser Upgrade Recommended

jobs.ac.uk has been optimised for the latest browsers.

For the best user experience, we recommend viewing jobs.ac.uk on one of the following:

Google Chrome Firefox Microsoft Edge