The nuclear envelope (NE) is central to cellular organization, influencing a myriad of processes, from gene regulation and repair to cell motility and fate. These critical roles of the NE depend on its elaborate structure, in particular on the organisation of its inner nuclear membrane (INM). The INM is continuous with the rest of the endoplasmic reticulum (ER), but contains a distinct set of proteins. Importantly, mutations in several INM proteins are linked to diseases such as muscular dystrophies and premature ageing.
In the last few years, the research group led by Pedro has discovered that in yeast cells the integrity and homeostasis of the INM proteome is maintained by a protein quality control system. This system selects against proteins that are aberrantly folded and dysfunctional, hence maintaining the normal functioning of the INM. However, the molecular mechanisms underlying this process are still unclear. With this grant, Pedro and his colleagues plan to systematically dissect protein homeostasis in the INM by combining various approaches such as proteomics, genetics and imaging. Gaining a deeper understanding into the turnover and regulation of proteins in the INM can shed light on the diseases caused by INM protein defects.
Pedro was delighted to hear the news, saying: “This is simply fantastic! This grant will allow us to expand our yeast work into mammalian cells, which have a much more complex and dynamic nuclear envelope. This grant will also help us solidify my group at the Dunn School, to where we moved a couple of years ago.”
To learn more about research done by the Carvalho lab, please visit: https://www.path.ox.ac.uk/content/pedro-carvalho
For more information about the ERC Consolidator Grant, check out this webpage: https://erc.europa.eu/funding/consolidator-grants
Written by Sheng Kai Pong