Job Description

Дата канвертавання24.04.2016
Памер27.84 Kb.

Unit Name:

Human Genetics Unit


Chromosomes & Gene Expression – Meehan Group

Job Title:

Career Development Fellow

Salary from :

£26,022 pa




Fixed-term 2 years

Funded by MARCAR

Reports to:

Programme Leader

Working Hours:

Full-time 36 hours

Class of appointment:


Post Number

Overall Purpose:

We are offering a 2 year Career Development Fellowship (CDF) which is a training and development position for post-doctoral scientists. Applicants will have recently completed their doctoral studies.

Project Title : The liver epigenome and its response to Non Genotoxic Carcinogen (NGC) exposure.

The aim of the MARCAR project is to identify early biological indicators ("biomarkers") that can be used to predict the effects of Non Genotoxic Carcinogen (NGC) exposure. These compounds are not cancerous directly, i.e. not genotoxic. Instead they perturb metabolic processes such as increased cell division that predispose to cellular transformation. Drugs that induce such cancers are NGC’s. A principle aim of the project is to identify early biological indicators (biomarkers) that can be used to predict the effects of NGC exposure. The liver is the major target organ for such drug-induced tumours and the MARCAR project aims to develop early markers of this carcinogenic risk.

The conversion of normal cells into cancer typically involves several steps resulting in the acquisition of unlimited growth potential (immortality). Both genetic and epigenetic changes have been detected in a number of different cancer cell types. Epigenetics is the study of inherited changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence. Generally, these changes lead to the activation of oncogenes and the inactivation of tumour suppressor and pro-apoptotic genes. A number of tumour suppressor genes have been shown to be silenced by promoter DNA methylation, where and how epigenetic alterations cooperate with genetic changes during the transformation process is of great interest.


We want to elucidate if DNA modification (5-methylcytosine and 5-hydroxymethylcytosine) patterns are altered in liver after short term exposure to Non Genotoxic Carcinogens (NGC) and if these predispose to cellular transformation. We will utilize DNA methylation and 5-hydroxymethylation enrichment techniques coupled with array technologies to determine their genome wide patterns in normal and treated rodent livers that will be provided by consortium partners. This will be a collaborative high-throughput project that will at the same time address basic biological processes. The attachment of a methyl group to cytosine (and subsequent hydroxylation) is an ancient mechanism that influences use and storage of genetic information. The process of DNA methylation is regulated by cytosine specific methyltransferases that establish or maintain methylation patterns at defined genomic regions and by demethylation functions that control general or target-specific removal of methylation. DNA modification plays a crucial role in gene regulation and in determining the competence of a gene to be expressed. Many genes contain methylation-free regions that favour their activity, while others are marked by DNA methylation in certain cell types to restrict their activity. Cancer development is often associated with mistakes in DNA methylation patterns inhibiting expression of essential genes or facilitating expression of detrimental genes. Among animals and plants, some enzymatic and targeting characteristics have been evolutionary preserved while others have diversified. A functional analysis of liver-specific DNA methylation functions will define how common and dynamic DNA methylation functions are. This will improve our understanding of target specificity and interplay between DNA methylation functions and toxic compound exposure.

Working Relationships:

The candidate will report to Dr. Richard Meehan and to work closely with other lab members to support of MARCAR objectives (

Organisational Position:

Main Duties:

You will participate in a challenging project aiming to investigate the molecular mechanisms and cellular pathways involved in the establishment of liver-specific DNA methylation patterns during the initial stages of NGC initiation and progression. The work will involve extensive use of mouse DNA samples and investigation of DNA/chromatin modifications by high throughput arraying techniques. Your responsibilities will include:

  • Co-ordination of sample analysis

  • Preparation and analysis of DNA samples by MeDIP and 5hMeDIP.

  • execution and/or supervision of downstream analysis

  • analyses of the temporal progression of epigenetic changes

  • participation in group meetings and seminars

  • participation in MARCAR meetings and consultation with MARCAR partners

  • maintenance of laboratory databases

  • Manuscript writing

  • Training of students and visitors in particular techniques

  • Presenting and discussion of results

  • Implementation and compliance with all health & safety issues, including COSH and risk assessments

  • Involvement in the smooth running and maintenance of the Chromosome and Gene expression section.

Key Responsibilities:

To be a primary worker on the MARCAR project and ensure it is carried out to a high technical quality, with efficiency and in a proper scientific manner.

Employment Checks:

Please note that final appointment will be subject to pre-employment health and security screening and references.

Level required : D

Additional Information:

Further information on MRC Human Genetics Unit can be found at:

Informal enquiries: or
Applications should be submitted electronically on our e-recruitment system at Please attach CV and covering letter with your application. If you do not have internet access or experience technical difficulties, please call 01793 301159, quoting reference number HGU10/364.
CV must be included with application

Closing date: 14 September 2010

Interviews will be held locally

Corporate/Local responsibilities & requirements:

The job holder must at all times carry out their responsibilities with due regard to the MRC’s:

Job descriptions should be reviewed on a regular basis and at the annual appraisal. Any changes should be made and agreed between postholder and line manager

The above lists are not exhaustive and the job holder is required to undertake such duties as may reasonably be requested within the scope of the post. All staff are required to act professionally, co-operatively and flexibly in line with the requirements of the post and the MRC.

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MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU Telephone +44(0)131 332 2471 fax +44(0)131 467 8456

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