An asymmetric and imprinted chromosome segregation mechanism organizes the bacterial nucleoid. (360G-Wellcome-080211_Z_06_Z)

Chromosome organization, replication and transmission to daughter cells underlie genome integrity and the life process. New microscopic methods have revolutionized understanding of chromosome dynamics in bacteria, and have revealed an unprecedented choreography of gene and macromolecular component position in time and in space. In recent work from the applicant s laboratory, an unexpected asymmetry in the chromosome segregation process has been revealed by studying the positioning and segregatio n of 20 different genetic loci in pairwise combinations; markers duplicate in the central region of the cell, where the replication machinery is located, with one sister segregating towards a cell pole and its sister remaining closes to midcell. This generates a translation symmetry [L-R; L?R ] organization of sister chromosomes. Underlying this asymmetric segregation is an imprinting process that directs the asymmetry in the same direction through generations. The purpose of this proposal is to provide RA1A funding for an ex-Wellcome Prize Student whose pioneering D.Phil work led to the demonstration of asymmetric segregation. By using a combination of genetics and biochemistry, in combination with microscopy, this work will reveal the molecular mechanisms responsible for chromosome organization and asymmetric imprinted segregation