In mammalian development, embryonic stem cells (ES) differentiate, i.e. change into more specialized cell types. Martin Leeb’s research focuses on identifying and studying molecular processes that drive and regulate proper differentiation. Scientists have already identified a cohort of such differentiation mechanisms. One such process is nonsense mediated mRNA decay (NMD), which is a surveillance mechanisms that helps maintain cellular stability, known as homeostasis.

During gene expression, a large family of RNA called Messenger RNA (mRNA) conveys genetic information from the DNA to another part of the cell, the ribosome. There the mRNA triggers a biochemical process called translation that eventually synthesizes proteins. These mRNAs also contain so called stop codons that signal termination of translation. Through gene mutation these stop codons are sometimes premature or erroneous, which can cause the translation of abnormal proteins. NMD maintains cellular homeostasis by eliminating mRNAs that contain premature termination codons.

Apart from this function, NMD could also play a bigger role in differentiation, which the Leeb group aims to understand: “We have identified the nonsense mediated mRNA decay pathway to be an essential component to achieve a fine-tuned response to differentiation cues. In this project, we aim to delineate the exact mode of action by which this NMD – usually considered a housekeeping mechanism – can be coopted by the differentiation machinery to regulate differentiation”, Martin Leeb concludes.