Main Job Purpose
A BBSRC funded post-doctoral position in the lab of Jonathan Hanley is available to assist in investigating the regulation of microRNA-mediated local translation in neurons by Argonaute phosphorylation. MicroRNAs (miRNAs) are small noncoding endogenous RNA molecules that repress the translation of target mRNAs through complementary binding in the transcript 3’-untranslated region (3’-UTR). A number of miRNAs have been shown to be involved in specific forms of learning and memory, and dysfunction of miRNAs is implicated in neurological and neuropsychiatric diseases including Alzheimer’s, Huntington’s and Schizophrenia. Argonaute (Ago) proteins associate with miRNAs as well as numerous additional proteins in RNA-induced silencing complexes (RISCs) to direct translational repression of target mRNAs. Ago2 can be phosphorylated at a number of residues, some of which regulate Ago2-protein or Ago2-RNA interactions in non-neuronal cell lines. Beyond our work, the regulation of RISC protein-protein interactions and hence miRNA activity by Ago2 phosphorylation remains unexplored in neurons, and we propose that this is a key mechanism that mediates the rapid and local modulation of miRNA-mediated gene silencing in dendrites close to stimulated synapses.
The post holder will employ molecular and biochemical approaches as well as fixed and live cell imaging techniques to study local translational repression via miRNAs, protein-protein interactions and dendritic spine morphology in neuronal cell culture models of synaptic plasticity and/or neurodegenerative disease. In addition, the post holder will develop tools for studying these mechanisms in vivo.
Main Statement of Responsibilities
- You will be expected to advance an original neuronal cell biology research project. Although guidance will be given as to the direction of the research and in techniques used, you will be expected to make a significant contribution to the development of the project.
- You will employ a range of biochemical and molecular approaches to:
- Use proteomics approaches to define novel mechanisms for the regulation of Ago2 function
- by phosphorylation following the induction of synaptic plasticity.
- Investigate synapse-specificity of translational repression via these mechanisms.
- Investigate a role for PICK1-Ago2 interactions in linking activity-dependent endosomal trafficking of AMPARs to translational repression.
- Characterise a proposed transgenic mouse line (biochemically and using basic behaviouraltests).
- Develop viral vectors for manipulating Ago2 function in vivo.
- Some of the above might be done in collaboration with PhD students.
- In addition, depending on prior experience and as appropriate, you will share expertise and contribute to other projects within the lab and with collaborators.
- Successful applicants will require knowledge of, or have extensive experience in, at least three of the following areas:
- Immunocytochemistry, live and fixed cell confocal imaging. Prior microscopy experience will be essential for this role.
- Molecular biology and biochemistry expertise, viral vector generation, etc.
- Proteomics approaches.
- Primary neuronal cell culture techniques.
- RNA biology and the study of translation.
- Contribute to the management and direction of the research project and relevant research collaborations.Assist in the day-to-day running of the research laboratory, including taking responsibility for specific house-keeping tasks.Participate in collaborative projects with other group members.
- Meet with the head of the group on a weekly basis and give updates/progress reports to our interdisciplinary research groups.
- Assist in the supervision of Ph.D. M.Sc. and B.Sc. students.
- Contribute to review and methods articles as required.
As this role is a Pathway 2 (Research) role, there are no formally specified teaching duties required
of the role-holder. However, other commitments permitting, the role-holder may be given
development opportunities to undertake activities such as teaching on Masters and Doctoral
programmes and/ or supervising MSc dissertations within the School of Biochemistry, as
- PhD in Neuroscience, Biochemistry, Cell Biology or discipline relevant to the project.
- Must be able to work as part of an interdisciplinary research team and discuss and
- communicate ideas enthusiastically, clearly and effectively to co-workers.
- Evidence of the ability to present research findings at national and/or international meetings
- Readiness and ability to contribute novel ideas to the project, learn new techniques as the
- need arises and overcome experimental difficulties.
- Willingness to supervise undergraduate project students and summer research students.
- Demonstrated capability to maintain proper laboratory documentation
- PhD in local translation or RNA biology.
- Experience of writing manuscripts for publication in leading international journals.
- Evidence of the ability to orally present research findings at national and/or international
- meetings. Participation in outreach activities.
Role holders at this level are concerned with assisting an individual research leader or team to conduct a particular study (or group of studies). They will generally be involved in data generation and/or collection using standard and well-defined methods developed by others. They will be working under close supervision by, and direction from, a more senior researcher, who will be ultimately responsible for the project. This may be the entry level for some staff who are expected to train and/or develop to take on more senior researcher roles. Role holders will be provided with academic and pastoral support within the department (including counselling on realistic career opportunities) and training will be available designed to develop their competences and to prepare them to take on more responsibilities associated with a higher grade.
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