Research Fellow

Full-time, 35 hours per week

Fixed term for 3 years, with the possibility of extension

We have one Postdoctoral research opportunity working within the laboratory of Professor Javier F. Caceres at the MRC Human Genetics Unit in Edinburgh, funded by the Medical Research Council.

The Opportunity

We aim to understand regulatory mechanisms related to the processing and quality control of RNAs in vivo, focusing on the Nonsense-mediated decay (NMD) pathway. NMD targets mutated mRNAs harboring premature termination codons (PTCs) for degradation, but also regulates the stability of many cellular transcripts. Importantly, NMD modulates the phenotypic outcome of genetic disorders caused by frameshift or nonsense mutations that generate PTCs. Thus, a better understanding of its regulation in vivo is needed for designing strategies to modulate the NMD response for therapeutic use.

Research objectives

We have developed a novel transgenic mouse model harboring an NMD sensor, which will allow to monitor the efficacy, tissue-specificity, and developmental regulation of the NMD response in vivo, with single-cell resolution. The project will use this mouse model to investigate the complex regulation and physiological relevance of the NMD pathway in vivo. We will also investigate changes in NMD activity in mouse models of human disease. A complementary project will develop genome-wide CRISPR screens in the liver to identify novel regulators of the NMD pathway. There is also the possibility of contributing to complementary projects on the mechanism and function of a localized Nonsense-mediated decay (NMD) response that regulates the expression of transcripts translated at the Endoplasmic reticulum (ER), which we termed ER-NMD (1).

- Longman et al. (2020) Genes Dev 34: 1075-1088

For additional lab references, see: Maslon et al (2019) EMBO J 38: e101244; Haward et al. (2021) eLife 10:e65104; Hug et al. (2022) RNA 28: 1224-1238

This position is part of a multidisciplinary team working on the molecular, biochemical, and cellular aspects of RNA processing in eukaryotes. The group is part of the MRC HGU and provides opportunities to develop research project skills and develop collaborative links with colleagues within the Institute and elsewhere. The MRC Human Genetics Unit is a highly multidisciplinary environment and is part of the Institute of Genetics and Cancer (IGC)

Further details of the Research group’s work are available at:
http://www.ed.ac.uk/mrc-human-genetics-unit/research/caceres-group

Your skills and attributes for success:

• PhD or equivalent in a relevant scientific discipline
• Experience in Biochemistry, Cell Biology and RNA processing, in particular related to mRNA translation
• Experience in embryonic stem cell biology
• Ability to communicate complex information clearly, orally and in writing
• Expertise in relevant approaches and models, analytical techniques and methods

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