Elucidating the mechanism of SMC complexes

The segregation of bacterial chromosomes is orchestrated by the co-ordinated actions of ParB and condensin [1]. ParB (also called Spo0J) is a site-specific DNA binding protein that binds at and around parS sequences near the origin of replication to form “ParB networks” which define the bacterial centromere [2]. These recruit condesin, a heteropentameric ATPase composed of SMC and the ScpAB2 subcomplex, which subsequently threads onto the centromere and juxtaposes the left and right arms of each chromosome to facilitate their separation. It is thought that this threading activity of condensin, which remains very poorly understood in mechanistic terms, may underpin global chromosome organisation in all domains of life.

In this project, you will study the structure, function and mechanism of condensin and its loading factor ParB using Bacillus subtilis as a model system. The work will be interdisciplinary involving both bulk and single molecule techniques, and will also involve working alongside colleagues in collaborating labs (see [2] for an example). You will address the system at various scales by incorporating methods ranging from in vitro analysis of individual proteins or protein domains to imaging of the supramolecular assemblies formed at bacterial centromeres in vivo.