Molecular mechanisms of bacterial chromosome compaction and segregation

Bacteria typically store their genetic information in a single circular chromosome that is several million DNA bases long.  In order to maintain and duplicate this chromosome, called the nucleoid, bacteria must accomplish two major feats of structural engineering:  First, a giant 1.5 millimeter-long DNA molecule must be packaged into a bacterial cell that is over a thousand times shorter.  Second, newly replicated sister chromosomes must be disentangled and separated without the advantage of the sophisticated mitotic machinery that is present in eukaryotic cells.  Work over the last several decades has identified a number of nucleoid-associated proteins (NAPs) that play essential roles in these processes, yet it remains unclear how various NAP-DNA interactions collectively regulate nucleoid architecture. In collaboration with David Rudner’s lab here at HMS, we are  investigating the molecular mechanisms by which nucleoid-associated proteins from the model gram-positive bacterium Bacillus subtilis organize and segregate the bacterial chromosome.