Looking deeper into the cell’s quality control mechanism

Professor Christiane Berger-Schaffitzel from the University of Bristol’s School of Biochemistry has won a £1.5m Wellcome Trust Investigator Award in Science Application to study an essential quality control mechanism in cells.

The mechanism, known as nonsense mediated mRNA decay (NMD) is of fundamental importance for cellular function in health and disease. Messenger RNA (mRNA) carries the genetic information from DNA for protein production inside cells. However, at times mRNAs contain errors which can give rise to shortened proteins, these can be toxic to cells and cause severe disease. Fortunately, cells have devised NMD to recognise and eliminate some faulty mRNAs. Despite the importance of the mechanism it is still do not understood how faulty mRNAs are recognised and marked for elimination.

The University of Bristol reports the award will be used to validate a recent discovery by Christiane Berger-Schaffitzel’s lab, showing the role of a key protein in the recognition of faulty mRNAs. By using electron cryo-microscopy (cryo-EM) the team will be able to visualise, at near-atomic resolution, how this protein and others interacts with faulty mRNA and to discover their impact on health and disease.

Christiane Berger-Schaffitzel said “I feel very honoured to receive a Wellcome Trust Investigator Award. I am excited to be given the chance to contribute to our understanding of NMD, a mechanism linked to more than 20 percent of the genetic diseases caused by single-base pair mutations.”

Failure of cells to degrade faulty mRNAs are implicated to be the starting point for many genetic diseases, including non-syndromic intellectual disability, autism and schizophrenia. Understanding the molecular events triggering NMD will be instrumental for the development of future therapies to treat such conditions.

To succeed the team will bring to bear a whole array of sophisticated tools in which they excel, ranging from molecular and synthetic biology, to state of the art high resolution structure determination by cryo-EM. They will use the University of Bristol’s newly acquired £2.2m microscope in the GW4 Cryo-EM Facility, funded by Wellcome Trust Equipment Grants, spearheaded by Christiane Berger-Schaffitzel.

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