BBSRC MRes/PhD studentship: Biological Function of a Ubiquitous RNA Ligase
- Doctoral Training Partnership (DTP)
- Reference Code: CB077
Name of the supervisors
Prof K Gerdes and Dr N Zenkin, Institute for Cell and Molecular Biosciences
This studentship is sponsored by BBSRC as part of the Doctoral Training Partnership (DTP)
Duration of the award
4 years (MRes Medical and Molecular Biosciences followed by a three-year PhD). Alternatively a 3 year PhD for candidates with an MRes or MSc.
All organisms contain RNA ligases that can repair damaged RNA. However, the biological roles and natural substrates of these RNA ligases are in many cases unknown. RtcB is a ubiquitous RNA ligase found in Bacteria, Archaea and Eukaryotes of unknown biological function. The main aim of the project is to understand the biological function of RtcB in E. coli and extend the analysis to higher organisms. The project encompasses the following parts:
(i) Identification of the biological substrates of RtcB. RtcB of E. coli can seal broken tRNA stem-loop structures, raising the possibility that RtcB helps the cells recover from stress conditions that damage RNA. Moreover, when RtcB is expressed in yeast, RtcB can catalyse tRNA and mRNA splicing. Thus, RtcB's substrate specificity is not restricted to tRNA raising the possibility that the ligase has a general function as an RNA-repair enzyme. Using in vitro ligation assays, we will aim to determine the substrate specificity of RtcB. Using in vivo assays in which we express natural RNAs that are damaged at known positions, we will aim to define the natural substrates of the ligase. Combined, these analyses are likely to reveal the substrate specificity of the ligase.
(ii) Regulation of the rtcAB operon. The rtcAB operon is activated by RtcR, a simga54 dependent activator. We will use gene fusion technologies to analyse how rtcAB is regulated.
(iii) Identification of the signal that induces rtcAB transcription. RtcR senses an unknown cellular signal and activates transcription of RtcB. Remarkably, RtcR is highly conserved in a wide spectrum of bacteria, suggestion that the signal sensed by RtcR is general. We will use the reporter fusions generated in subproject (ii) to screen for external conditions and internal conditions in an attempt to identify the signal sensed by RtcR.
Value of the Award and Eligibility
Depending on how you meet the BBSRC's eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees at the UK/EU rate and an annual stipend of £13,590 (2011/12). A partial award covers fees at the UK/EU rate only.
Candidates should have or expect to achieve a First Class or 2:1 Honours degree in a relevant science subject. Students who also have further research experience and/or a further qualification such as for example an MRes will be considered for a three year PhD.
How to Apply
You must complete the University's postgraduate application form . Select "Master of Research/Doctor of Philosophy (Medical Sciences) - Cell and Molecular Biosciences" as the programme of study. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CB077.
Closing date for applications
Prompt application is advised as this post is only available until a suitable candidate is appointed
Prof K Gerdes, email@example.com , +44 (0) 191 208 3230