Role of p27 and K-Ras in the oncogenesis

Job summary

A postdoctoral position is available in Professor Oriol Bachs laboratory. The position involves working with a team of scientists studying the role of the proteins p27 (Kip1) and KRas in the oncogenesis.

The programme is a continuation of work recently published in the Journal of Cell Biology 2009 23;184(6):863-79. by Lu A., et al. which has provided evidences indicating that KRas moves from plasma membrane to early and late endosomes to finally be degraded in the lysosomes. On these different intracellular platforms KRas generates signal outputs and thus activating different effector proteins.

Briefly, KRas is a classical oncogene that participates in the regulation of many different cellular functions as gene expression, survival, motility, proliferation etc. It is mutated and consequently hiperactivated in many human tumours. Our group is interested in the analysis of the regulatory role of KRas in different intracellular platforms (mainly the endocytic platforms) and in the analysis of the relevance of this regulation in the development of tumors.

Moreover, the group is also working on the role of p27(Kip1) in the oncogenesis. P27 is a member of the Cip/Kip1 family of cdk inhibitors. It has been observed that tumours with low levels of p27 are significantly more aggressive. Recently, it has been shown that this role in oncogenesis is independent of its ability to inhibit cyclin-cdk complexes. Our group is working in the identification of the putative new cdk-independent functions of p27 that can be involved in tumorigenesis. Our results indicate that p27 is also a transcriptional regulator of genes involved in proliferation but also in RNA processing, translation and respiration. Finally, we also found that p27 plays a role in the regulation of translation of a specific subset of proteins. Preliminary evidences indicate that these new functions of p27 might play a role in tumorigenesis.

The purpose of this programme of work will be:

• 1) To identify KRas effectors in early and late endosomes and the analysis of their activation after mitogenic stimuli.
• 2) To analyse the mechanisms by which p27 regulates transcription of specific p27-target genes and how alteration of these mechanisms can participate in the development of tumors.

The project is likely to involve some or all of the following techniques:

• Chromatin immunoprecipitation
• Transcriptional luciferase assays
• Affinity chromatography
• Immunocytochemistry
• Western blotting
• Expression microarrays
• Proteomics

Main Duties

To conduct research investigating the role of p27 and KRas in the tumorigenesis.

Duties and Responsabilities

• To contribute to the design and planning of experiments in relation to this project
• To develop a thorough understanding of the research field and be involved in the intellectual decision making process required for successful completion of the project
• To set up and run experiments in consultation with the Principal Investigator
• To record, analyse and write up the results of experiments and ensure that laboratory notebooks are kept fully up to date as a formal record of the research
• To prepare and present findings of research to the Principal Investigator and other members of the centre
• To prepare progress reports on research
• The post holder may be required to perform some limited teaching and/or supervision of other members of staff and/or students, under the guidance of the Principal Investigator
• Responsible for ensuring that designated equipment is safe and maintained in good working order
• As duties and responsibilities change, the job description will be reviewed and amended in consultation with the post holder
• The post holder will carry out any other duties that are within the scope, spirit and purpose of the job, as requested by the Principal Investigator

Person specification

Knowledge and Qualifications

Essential:

• Undergraduate degree in a life science discipline.
• PhD in an appropiate life science discipline

Desirable:

• Basic knowledge of Biochemistry, Molecular Biology and Cell Biology
• Publications in high impact factor peer reviewed journals

Skills

Essential:

• Abilitity to develop ideas logically and design experiments to test hypotheses
• Ability to modify and apply new methods to advance a project
• Ability to analyse and write up data for presentations and publications
• Ability to present complex information effectively to a range of audiences
• Effective written and verbal communication skills
• Ability to meet deadlines
• Record of delivering high quality research

Desirable:

• Research skills in general molecular and cellular Biology techniques.
• Expertise in chromatin immunoprecipitation
• Ability to direct junior members of the laboratory in simple laboratory procedures

Experience

Essential:

Experience of working in a research environment

Desirable:

Experience of multi-disciplinary working

Personal Qualities

Essential:

• Commitment to high quality research
• Ability to work effectively as part of the team
• Ability to work independently and to use own initiative when required

(Read eligibility criteria)