Overview of the role
Hypoxia is a key component of cancer pathology, and a wide range of cardiac, pulmonary, vascular and inflammatory diseases.
The hypoxia biology laboratory has discovered a series of enzymatic oxygen sensors that regulate transcriptional responses to hypoxia by post-translational hydroxylation of specific prolyl and asparaginyl residues in the transcription factor, hypoxia inducible factor (HIF) (1-3).
These oxygen sensors belong to a family of enzymes known as 2-oxoglutarate-dependent dioxygenases. Although several members of this family have been implicated in human disease, the roles they play in hypoxia signalling and pathological processes in vivo remains elusive. To facilitate discoveries in this area we aim to develop a generic transgenic vector for shRNA knockdown of 2-oxoglutarate-dependent dioxygenases.
You will be responsible for developing inducible shRNA transgenic vectors, for testing their efficacy in embryonic stem cells, and for generating and phenotyping transgenic animals. You will use a range of molecular, biochemical, cell biological and transgenic techniques to develop these vectors and to study the role of 2-oxoglutarate-dependent dioxygenases in hypoxia signalling and pathological processes in vivo.
Responsibilities/duties
- To undertake the research project described above by performing laboratory research involving a wide spectrum of molecular, cellular and transgenic approaches.
- To contribute fully to laboratory meetings and discussion of the aims and objectives of the group’s work.
- To keep up-to-date with relevant literature.
- To be responsible with others for biological and general safety in the laboratory.
- To work closely with other group members as part of a team and to communicate progress and difficulties in the research project effectively to others.
- To participate and contribute directly to scientific discussions with members of the laboratory and co-workers in other groups, both informally and at regular group meetings. To contribute to the publication of research findings in high quality journals.
- To attend appropriate scientific seminars and meetings and to remain up to date with developments in the relevant fields.
- To participate in the education and training of other staff and students as necessary and appropriate.
Essential
- A PhD in biochemistry or molecular biology.
- Experience in standard molecular biology techniques, including recombinant DNA cloning and protein and RNA analyses.
- Experience of embryonic stem cell culture and manipulation.
- Experience of RNA interference in mammals, particularly shRNA.
- Experience of animal husbandry.
- The ability to work as part of a team.
- The ability to design and execute experimental programmes.
Selection criteria
Essential
- A PhD in biochemistry or molecular biology.
- Experience in standard molecular biology techniques, including recombinant DNA cloning and protein and RNA analyses.
- Experience of embryonic stem cell culture and manipulation.
- Experience of RNA interference in mammals, particularly shRNA.
- Experience of animal husbandry.
- The ability to work as part of a team.
- The ability to design and execute experimental programmes.
