Title: Cell identity: an essential aspect of animal cell division.
Funder: The Academy of Medical Sciences

Abstract: Cytokinesis, the physical division of one cell into two, is critical for generating multicellular organisms. Errors in cell division can drive diseases, for example by causing genetic abnormalities that lead to cancer, and developmental defects due to loss of progenitor cells. Decades of research have generated a detailed understanding of how an ‘ideal’ cell divides. However, there is growing evidence that a cell’s identity, resulting from its developmental history and environment, may modify the cellular apparatus that is required to divide the cell. For example, a contractile ring normally divides the cell, by forming at the cell equator and constricting, pulling in the cell’s membrane. In contrast, my recent work shows that cells can divide in the absence of a normal contractile ring, but this process is dependent on specific factors related to cell identity. My hypothesis is that the requirement for the core the cell division machinery, previously thought of as conserved and essential, diverges between cells with different identities. The proposed research will use the nematode worm, C. elegans, to systematically investigate the role of two components of cell identity, signalling and polarity, in cell division, using the embryo and larva. Cell division and cell identity pathways will be disrupted using genetic and pharmacological tools. These tools will be combined with live-cell microscopy to characterise cell division machinery and dynamics. This project provides an exciting and timely opportunity to reassess and redefine our understanding of these fundamental and biomedical aspects of cell biology.

Lay abstract: Animals are made up of cells that carry out, either by themselves or in groups, all the functions that the organism needs to grow, live and reproduce. As all animals develop from just one cell (the fertilized egg), each cell divides in a dynamic process, from one into two, four, eight and so on. Cell division has been long-studied, allowing scientists to build up a detailed understanding of the cellular apparatus involved. This overview seemed consistent between different types of cells, suggesting that all cells divide in the same way. However, clinical and laboratory research has shown that division can occur when factors defined as essential for division are removed or mutated. Intriguingly, only specific types of cell divide under these conditions, suggesting a cell’s identity can affect its ability to divide. This is of critical importance because both cell identity and cell division are often disrupted in cancers. The proposed research will use a species of well-studied nematode worm, in which development can be tracked and monitored by microscopy. In this animal, each cell has a different identity depending on its ancestry and environment, making it the perfect model to investigate how identity affects division. We will use this system to test the hypothesis that specific cells in the organism can divide when the division apparatus is disrupted and determine how this is regulated by a cell’s identity. Given the important role cell identity and division have in disease, defining how they interact will be a fundamental biomedical advance.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE