Understanding asymmetric cell divisions at the onset of life
Application deadline: 21 January 2019
Start of PhD: 1 October 2019 (3.5 years)
To generate a complex organism from a single-cell embryo, cells divide asymmetrically acquiring structural and functional differences. This polarisation is essential for tissue and organ development and depends on the localisation of conserved effectors, notably PAR proteins, to discrete cell membrane domains. A wide range of developmental problems are associated with impaired PAR function (e.g. cardiovascular, neurodegenerative diseases and cancer). Consequently, understanding how PARs act is of great biological importance. Recently, we have shown that the activity of the PAR signalling component, aPKC-kinase, is not only critical for the polarisation programme but also creates the asymmetric domain of active PARs needed for the development of the early embryo. We are seeking an enthusiastic student keen to reveal the molecular mechanisms underlying this novel aPKC function. We will use a multidisciplinary approach, including genetic screens, proteomics, biochemical assays, genome editing, mathematical modelling and cutting-edge microscopy analyses. Studies will be performed in nematode C. elegans and mammalian model systems.
Campanale JP et al. Development and dynamics of cell polarity at a glance. J Cell Sci 2017 130: 1201
Rodriguez J et al. aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity. Dev Cell 2017 42: 400
Fievet B et al. Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy. Nat Cell Biol 2013 15: 103
Informal enquiries to Dr Josana Rodriguez (josana.rodriguez@ncl.ac.uk).
Apply here.