(BBSRC DTP) Single molecule live imaging of ribosome stalling during embryonic development

The correct regulation of gene expression is critical to multicellular life.  A key regulated step is mRNA translation; one regulatory mechanism is that ribosomes can stall on particular mRNA sequences until they are able to resume elongation or are released from the mRNA.  Understanding ribosome stalling is critically important, as it is associated with proteotoxic stress in cells and neurodegenerative diseases.  The aim of this project is to determine how ribosome stalling contributes to the regulation of translation during embryonic development.  To address this question, a combination of molecular biology, biochemical, developmental biology, live imaging, genome editing and computational approaches will be used.  We will exploit the Drosophila embryo as a model as it has several unique advantages that make it perfectly suited to this research.  These include its rapid life cycle, tractability, ease of manipulation, amenability to genetic and genome engineering approaches, as well as recent advances that allow transcription and translation to be imaged live and at single molecule resolution.  Firstly, existing data sets will be mined to identify mRNAs associated with ribosome pausing in the early embryo.  Then, for a subset of these mRNAs, the presence of stalled ribosomes will be verified biochemically using extracts prepared from the early embryo.  Following the validation of mRNAs with stalled ribosomes, we will exploit our ability to image translation at single mRNA resolution in the embryo in order to determine the translation kinetics on mRNAs with ribosome pause sites in vivo.  Finally, ribosome pause sites will be mutated to determine the effect of reduced ribosome pausing on early embryonic development.  Overall, findings from this research will provide new information about ribosome stalling, which is critical for cellular homeostasis and is misregulated in disease.   

Eligibility 

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.  

Before you Apply 

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How To Apply 

To be considered for this project you MUST submit a formal online application form - full details on eligibility how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/bbsrc-dtp/  

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]  

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