MSc by Research programme: The role of the CCR4-NOT complex in somite segmentation

This course allows you to work alongside our world renowned experts from the School of Life Sciences and gain a ’real research’ experience. You will have the opportunity to select a research project from a variety of thematic areas of research.

You will be part of our collaborative working environment and have access to outstanding shared facilities such as microscopy and proteomics. Throughout your year, you will develop an advanced level of knowledge on your topic of interest as well as the ability to perform independent research in the topic area. Alongside basic science training in experimental design, data handling and research ethics, we will help you to develop skills in critical assessment and communication. This will be supported by workshops in scientific writing, presentation skills, ethics, laboratory safety, statistics, public engagement and optional applied bioinformatics.

The period of study is one year full-time or two years part-time research, which includes two months to write up the thesis. Please apply via the UCAS postgraduate application form: https://digital.ucas.com/courses/details?coursePrimaryId=c735d826-42b6-ca1f-50db-2a3ac6f68718

During early embryogenesis the somites are formed during a process called segmentation. The somites will go on to form the bones and muscles of the skeleton. This a highly regulated process where somites bud off the rostral end of the presomitic mesoderm (PSM) at regular intervals. The timing of the process is thought to be regulated by a molecular oscillator, called the segmentation clock, that drives cyclic gene expression across the PSM with a periodicity that matches somite formation. The so called- clock genes belong to three signalling pathways; Notch, FGF and Wnt all of which are essential for development and many diseases, including a variety of cancers, are caused by abnormal signalling of three pathways. Quite a lot of research has been done on how the oscillating expression of the clock genes is switched on, however far less is known about how they are switched off and how the corresponding mRNAs and proteins are degraded at the correct times. This project would investigate the role of translation efficiency and mRNA stability in the regulation of the segmentation clock. A few papers show that the 3’ untranslated regions (UTRs) of some of the oscillating genes are required for correct segmentation patterns. UTRs of many mRNAs are critical for correct localisation, translation and mRNA stability. In a recent paper the critical role of the CCR4-NOT complex in the segmentation in zebrafish embryos was established. This complex can both repress translation and destabilise the mRNA via deadenylation. Research on the role of mRNA translation and stability in the regulation of the circadian clock shows that only some mRNAs encoding for oscillating proteins oscillate themselves suggesting that they are regulated at the level of translation efficiency. It would be interesting to investigate by which mechanism the segmentation clock genes are regulated and what the role would be of e.g. mRNA translation and stability, the CCR4-NOT complex, RNA binding proteins, miRNAs, long non coding RNAs and/or RNA modifications.