Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Membrane remodelling during mitotic exit

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding £1.9M
Period Oct 2017 — Oct 2022

In plain English

AI plain-English summary

Every time a cell divides, it must rebuild its nucleus from scratch—and scientists do not fully understand how. This project addresses a fundamental gap in knowledge about cell division. While researchers have mapped how chromosomes are separated, they know far less about how the cell’s internal compartments—its organelles—are split and reassembled. The work focuses on a protein machine called ESCRT-III, which reshapes cell membranes. The team will investigate how one of its components, CHMP7, attaches to the membrane of the endoplasmic reticulum (ER) and the nuclear envelope to help rebuild the nucleus after division. They will also explore whether chemical modifications to ESCRT-III control its assembly, and whether this machinery plays an unappreciated role in separating the ER during cell division. This is fundamental science with no immediate practical application. However, cell division goes wrong in diseases such as cancer, and the machinery that rebuilds organelles after division is a potential target for future therapies. Understanding how ESCRT-III works could also illuminate broader principles of how cells manage their internal architecture—knowledge that has, in the past, led to unexpected insights into infection, neurodegeneration, and drug delivery.

View original technical description
Cell division is of critical importance to cellular and organismal health, being essential for proliferation, growth and development, and is deregulated in disease states such as cancer. We will perform discovery-research to acquire new knowledge about cell division. Whilst we know much about how the genome is separated, we know far less about how cytoplasmic organelles are separated during division. I will explore the contribution made by a cytoplasmic membrane remodeling machinery, ESCRT-III, to organelle-separation and organelle-regeneration during mitotic exit. Additionally, we will discover new mechanisms by which the assembly of ESCRT-III can be regulated. Firstly, using a combination of structural biology, lipidomics and cell biology, we will identify how the ESCRT-III component CHMP7 binds to ER and nuclear-envelope membranes to enable ESCRT-III-dependent nuclear envelope regeneration. Secondly, we will use in-vitro and in-vivo assays to explore the role of ESCRT-III phosphorylation as a mechanism regulating ESCRT-III assembly. Lastly, we will discover how the ER is remodelled during mitotic exit. We will explore new roles for the ESCRT-III machinery in controlling ER-morphology, and will expose a hitherto unforeseen role for this machinery in regulating ER-separation during mitotic exit.

View the original record at the funder ↗

Researchers

Jeremy Carlton (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Remodelling of the Endomembrane System During Mitotic Exit
NEPhos_Phosphoregulation of ESCRT-III during nuclear envelope reformation
Membrane remodelling during cell division
Understanding the inheritance of the Endoplasmic Reticulum during cell division
Investigating the molecular mechanisms of nuclear envelope stability and repair

Original classification

Senior Research Fellowship Basic

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.