University of Manchester
Manchester, United Kingdom
Overall Purpose of the Role
Our current working hypothesis is that a network of integrated pathways coordinates protein synthesis and degradation enabling our cells to offset inherent defects, including misfolding and aggregation, and maintain protein homeostasis. The extremely hydrophobic transmembrane domains and targeting signals of membrane and secretory proteins pose a particular challenge, since inefficient subcellular delivery and defective membrane translocation result in the cytosolic mislocalisation of these notoriously aggregation prone precursors. These mislocalised proteins (MLPs) are rapidly removed via a specialised quality control pathway that employs novel adaptors and effectors to regulate their selective proteasomal degradation proteins (for a recent review see Casson et al., 2016. Biochem. Soc. Trans. 44: 796). Our next major goals are to establish the molecular details of MLP quality control, determine how it is coordinated with membrane protein delivery, and establish how it is integrated into global protein homeostasis.
This post requires a Biochemist/Molecular Biologist who will play a key role in progressing these studies by reconstituting key stages of MLP recognition and quality control using a combination of in vitro techniques. A key goal of your work is to uncover how similar classes of hydrophobic substrates are sorted towards either proteasomal degradation (MLPs) or membrane insertion (tail-anchored membrane proteins) respectively.
You will be working as part of a team who are studying “The quality control of mislocalised membrane and secretory proteins” funded by a five year Wellcome Trust Investigator Award in Science as of 1 March 2017.
- Take initiatives in the planning of research;
- Identify and develop appropriate strategies for the collection and analysis of data;
- Ensure the validity and reliability of data at all times;
- Maintain accurate and complete records of all findings;
- Prepare material for presentation in oral and poster formats;
- Present findings to colleagues and at conferences;
- Draft publications and prepare them for submission to refereed journals;
- Supervise practical work and advise students on techniques;
- Organise resources and display effective decision-making in support of research;
- Attend relevant workshops and conferences as necessary;
- Be an active team-member and a set positive example by showing a commitment to achieving results, encouraging and supporting junior members of the team and raising suggestions for continuous improvement;
- Work alongside the PI and other colleagues in a collegiate manner;
- Develop contacts and research collaborations within and beyond the Faculty;
- Promote the reputation of the laboratory.
- Undertake any necessary training and/or development;
- Actively read the scientific literature relating to the project;
- Maintain safe workplace practice and procedures in accordance with the requirements of Health and Safety legislation;
- Maintain an up-to-date knowledge of relevant statutory Health and Safety legislation and recommendations and attend safety training as required;
- Any other duties commensurate with the grade of the post as directed by PI.
Essential Skills, Knowledge and Experience
- Previous postdoctoral experience in Biochemistry, Molecular Biology or a closely related area;
- Hold a PhD and BSc in a Life Sciences discipline;
- Established expertise in the expression, purification and functional analysis of recombinant proteins;
- Development of functional assays and/or biochemical readouts for the study of biological pathways;
- Analysis of protein-protein interactions;
- Proven ability to plan efficiently, use your own initiative, optimise and progress your project and communicate your findings effectively;
- Appropriate IT skills and experience in preparing publication quality images and data;
- Excellent interpersonal skills and an ability to work with colleagues at all levels;
- Good written and spoken communication skills. A proven ability to keep accurate experimental records and maintain an up to date lab book;
- A willingness to contribute to the work of others by offering practical and intellectual help.
Highly Desirable Skills, Knowledge and Experience
- Previous experience with in vitro transcription/translation systems and the production of radiolabelled proteins;
- Experience with and understanding of relevant post-translational protein modifications, primarily N-glycosylation and polyubiquitination;
- Familiarity with quantitative immunoblotting;
- Previous research into the biogenesis of membrane and secretory proteins;
- Authorship of Peer reviewed research papers relevant to the project.