View Vacancy -- Postdoctoral Research Scientist - TOX - 712
The Medical Research Council Toxicology Unit, located at the University of Leicester, is an internationally renowned institution focussed on the delivery of field-changing mechanistic insights into toxicology and disease. The Unit is equipped with state-of-the-art facilities and offers excellent opportunities for postdoctoral development.
The Le Quesne lab has at the MRC Toxicology Unit over the past 3 years built up and developed cutting edge new quantitative in situ analytical methods, including multiple immunofluorescence, co-in situ hybridisation immunohistochemistry, quantitative single-cell image analysis, and hi-throughput tissue microarray-based technologies.
The Unit is currently in the process of transferring to the University of Cambridge. Legal transfer will take place in March 2018; the physical relocation is expected to take place in early 2020.
We are looking to appoint an enthusiastic Research Scientist to join the translational control in tumour biology group led by Dr. John Le Quesne, to work on a large consortium program grant funded by Cancer Research UK. The program title is “Targeting dysregulated translational control in the tumour environment”, and is a collaboration with Professor Martin Bushell (MRC Toxicology Unit) and Professors Sansom and Norman from the CRUK Beatson Institute.
The project builds directly upon ongoing work in the Le Quesne lab, and will suit a postdoctoral researcher with experience of and an interest in translational control in cancer.
Oncogenes are exquisitely dependent upon the eIF4F initiation complex, which unwinds mRNA structure and facilitates ribosome recruitment, for their translation. It acts as a signalling hub positioned at the end of several mitogenic pathways, and its upregulation is a common feature of malignancy and leads to drug resistance.
The effector component of the eIF4F complex is the mRNA helicase eIF4A, and inhibition of this protein shows dramatic and well-tolerated anticancer activity in animal models. eIF4A possesses two paralogues: the widely studied eIF4A1, and the highly similar eIF4A2, which are often assumed to be functionally redundant. However, our recent data show divergent functions and expression patterns of these two proteins. eIF4A1 is required for translation initiation and cellular proliferation; its expression defines proliferative regions within tissues and tumours, and is a predictor of poor outcome in many cancers. eIF4A2 is expressed in mature differentiated and secretory cells and tumour stroma, induces growth arrest, and predicts good outcome.
eIF4F activity is critical for driving malignant gene expression programs in tumours, and any attempt to target eIF4F therapeutically will require in-depth mechanistic understanding of this process.
We are applying a combination of the latest quantitative in situ and cell biological methods to fully elucidate how these essential proteins contribute to normal and abnormal biological processes.
The main aims of the project will be:
1. To quantify the expression of the components of the eIF4F complex, and to assess functional complex assembly, in malignant cells. This will be approached with cutting edge single-cell quantitative methods in primary tumour tissues, ensuring relevance to real tumour biology.
2. To similarly measure the downstream effects of eIF4F complex activity and eIF4A isoform-specific pathways at the single cell level in malignant cells.
3. To mechanistically relate these in situ measures of translational reprogramming to genomic changes in human tumour collections, and also to key hallmark behaviours of tumour cells.
We will work out how the eIF4F complex, the gatekeeper to almost all protein synthesis, is dysregulated in human tumours. We will understand how translation dysregulation contributes to phenotypic plasticity in cancer cells in human tumours, and how it interacts with genomic changes to drive malignancy.
All these findings will help us to better therapeutically target translation initiation in cancer, and crucially to identify patient groups who are most likely to benefit from these approaches.
The post holder will report directly to Dr. Le Quesne but is expected to work closely with other members of the group and group members at both the MRC Toxicology Unit in Leicester and Glasgow CRUK Beatson Institute. It is important to be able to work efficiently as part of a team and to collaborate effectively with colleagues.
Main duties / key responsibilities:
Within the overall direction of the programme of the group, and in discussion with Dr. Le Quesne, them post-holder will make a significant input into determining the direction of a project targeting dysregulated translational control in the tumour environment.
-To develop and apply a broad range of in situ analytical techniques in order to pursue the research objectives of the group.
-To participate in collaborative research, both within and external to the Toxicology Unit.
-To be actively engaged in the dissemination of new research results in the form of scientific papers.
-To present scientific work at seminars within the Unit and at external meetings where appropriate.
-To communicate and collaborate with others to develop the most appropriate methodologies, and to receive training in the use of relevant experimental techniques.
-To contribute towards the smooth running of the group including the effective use of resources, training of others e.g. visiting workers/students and taking responsibility for the use of communal facilities.
-To contribute to the Unit’s mission in the public engagement of science.
This post is of a finite duration and offers no guarantee of continued employment with the MRC.
Education / Qualifications / Training required:
- PhD in a biological sciences subject, particular molecular biology, cell biology, cancer biology, or molecular pathology. Experience of RNA biology / translation control is vital, and previous histological or other image-based cell biology methods would be advantageous.
- An understanding of the basics of translational control.
- A basic understanding of tumour biology.
- Basic statistical analyses as applied to large datasets
- Experience or training in bioinformatics
- Training in microscopic tissue interpretation
- Experience with survival analysis
Previous work experience required:
Advanced RNA biology techniques OR quantitative in situ histological methods
Knowledge of techniques aimed at assessing translation control, particularly deep-sequencing approaches (ribosome profiling) or array based methods.
Statistical data analysis
- Microscopic interpretation of tissues
- Quantitative histopathological methods
- Work with cancer models
- Statistical survival analysis (Cox/Kaplan-Meier methods)
- Bioinformatic/statistical data handling expertise (eg R, Stata software packages)
- Knowledge and experience:
- Proven skills in working independently to solve experimental problems
- Ability to establish new techniques in the laboratory
- Experience of training others ‘on the job’ and ability to write manuscripts for international journals.
- Personal skills/behaviours/qualities:
- Vision and ability to plan and manage projects over the medium term
- Able to demonstrate leadership ability within their research
- Drive and focus to work at highly competitive international level with full commitment to publication of data
- Strong commitment to team work
- Able to collaborate and provide advice to other researchers both inside and outside the Unit
The MRC is a great place to work and progress your career, be it in scientific research or the support functions.
The MRC is a unique working environment where our researchers are rewarded by world class innovation and collaboration opportunities that the MRC name brings. The MRC is an excellent place to develop yourself further and a range of training & development opportunities will be available to you, including professional registration with the Science Council.
Choosing to come to work at the MRC means that you will have access to a whole host of benefits from a final salary pension scheme and excellent holiday entitlement to access to employee shopping/travel discounts and salary sacrifice cycle to work scheme and childcare vouchers, as well as the chance to put the MRC on your CV in the future.
Our success is dependent upon our ability to embrace diversity and draw on the skills, understanding and experience of all our people. We welcome applications from all sections of the community irrespective of gender, race, ethnic or national origin, religion or belief, sexual orientation, disability or age. As "Disability Confident" employers, we guarantee to interview all applicants with disabilities who meet the minimum criteria for the vacancy.
Final appointments will be subject to pre-employment screening.
This opportunity is closed to applications.