Skip to main content

This job has expired

PhD studentship: Identification of genetic targets of acquired uniparental disomy

Employer
Global Academy Jobs
Location
United Kingdom
Closing date
Jun 30, 2016

Job Details

PhD studentship: Identification of genetic targets of acquired uniparental disomy

Human Development & Health

Location:  Southampton General Hospital
Closing Date:   Thursday 30 June 2016
Reference:  733716AF

Lead Institute / Faculty: University of Southampton / Faculty of Medicine

Main Supervisor: William Tapper

Other members of the supervisory team: Nick Cross and Andy Chase

Duration of the award: 36 months (Start date: 1st October 2016, End date: 30th September 2016)

 

Project description:

Aims and summary

The identification of somatic genetic abnormalities is critical to understand the biology and development of cancer. This application aims to identify and understand genes that are mutated or abnormally expressed in association with a particular type of somatic chromosomal abnormality termed acquired uniparental disomy (aUPD). We will focus on chromosomal regions that we have previously identified as recurrent abnormalities in patients with clonal myeloid disorders. Remarkably, these regions of recurrent aUPD are also seen in apparently healthy elderly individuals, albeit at a much lower frequency. This observation provides the opportunity to survey data collected from large numbers of individuals, thereby facilitating the detection of rare abnormalities.The application is multi-disciplinary, bringing together bioinformatics of large genomic datasets and laboratory based analyses, and will provide novel insights into leukaemogenesis that will impact on clinical practice.

 

Plan of investigation and methodology

Our preliminary analysis has determined that aUPD is associated with driver mutations in specific genes and that such mutations can be identified by whole exome sequencing (WES) of cases affected by the same region of aUPD (Ernst et al 2010; Grand et al 2009; Chase et al 2015). Since individuals with specific regions of aUPD are uncommon, we propose to exploit the large and growing collections of WES and WGS data that are being accumulated in various databases. We will interrogate this data to identify individuals with aUPD and then focus on identifying mutated genes associated with those regions.

We currently have access to whole exome sequencing (WES) data from 5090 patients with schizophrenia and 500 local cases. In addition to these WES datasets from patients without cancer, we have WES data from 20 patients with haematological malignancies and aUPD and further datasets will be accrued during the course of the project (including data from the 100K genome project) with the aim of accumulating >15,000 cases. A range of methods  will be used to analyse these datasets, identify regions of aUPD and the underlying somatic mutations involved in cancer (eg loss of heterozygosity, B-allele frequency segmentation, copy number analysis, GATK, CRISP, LoFreq, and VarScan etc). The functional significance of these somatic mutations and the genes they effect will be investigated by detailed informatic and, for an appropriate candidate, laboratory based analyses. It is likely that the project will evolve to include development and application of other informatic tools, for example analysis of RNAseq and GWAS data.

 

Research Environment

The student will join Nick Cross’s research group and the Genomic Informatics group (Will Tapper) and will utilise the University’s high performance computing facility, Iridis4. These research groups have established an international reputation for their work aimed at understanding myeloid leukaemias and translation of research findings into clinical practice. These groups collaborate with and support numerous applied projects, including major programmes in inflammatory bowel disease, breast cancer, and the 100K Genomes Project. The student will be trained in the theory and analysis of next generation sequencing, genome wide association studies, genetic epidemiology, practical data analysis including integration of multiple datasets and laboratory based analysis.

Please contact:  William Tapper (W.J.Tapper@soton.ac.uk)

Person Specification:

We seek an outstanding student with the equivalent of a first class or upper second class degree in a relevant discipline. Candidates with a Master’s degree are particularly encouraged to apply. The selected candidate will have excellent organisational and communication skills and be a keen contributor to a multidisciplinary team. A background or strong interest in bioinformatics, genomics and cancer biology is desirable

The successful candidate is likely to have the following qualifications, skills and experience:

  • A 1stor 2:1 undergraduate degree in a relevant discipline and/or second degree with a related Masters
  • Knowledge of Next generation sequencing and relevant software (e.g. Whole genome/exome/transcriptome sequencing, Genome Analysis Toolkit, Samtools etc)
  • Proficiency in Bioinformatics and familiarity with command line operating systems (e.g. Unix/Linux environment)
  • Fluency in programming (e.g. Python, perl, C)
  • Experience of statistical packages (e.g. R, Matlab, Stata, SPSS)
  • Able to work independently and as part of a team, organise own research, develop original techniques, and meet deadlines and quality standards
  • Communicate new and complex information effectively, both verbally and in writing, engaging the interest and enthusiasm of the target audience
  • Able to present research results at group meetings and conferences
  • Able to write up research results for publication in leading peer-viewed journals

 

Funding information:

Funded by Bloodwise Programme Grant ‘The Molecular Pathogenesis of atypical Chronic Myeloid Leukaemia and related conditions’ and the University of Southampton PGR scholarship in the Faculty of Medicine

 

Administrative contact and how to apply:

Apply using the link below.

You should enter William Tapper as your proposed supervisor. To support your application provide an academic CV (including contact details of two referees), official academic transcripts and a personal statement (outlining your suitability for the studentship, what you hope to achieve from the PhD and your research experience to date).

Informal enquiries relating to the project or candidate suitability should be directed to William Tapper (W.J.Tapper@soton.ac.uk).

Closing date:30th June 2016

Interview date:  15th July 2016

Company

Global Academy Jobs works with over 250 universities worldwide to promote academic mobility and international research collaboration. Global problems need international solutions. Our jobs board and emails reach the academics and researchers who can help.

"The globalisation of higher education continues apace, driving in turn the ongoing development of the global knowledge economy, striving for solutions to the world’s problems and educating a next generation of leaders and contributors."

Company info
Website

Get job alerts

Create a job alert and receive personalized job recommendations straight to your inbox.

Create alert