Project Summary
My lab studies the molecular biology of archaeal microorganisms. Our rationale for doing so lies
in the evolutionary relationship between archaea and eukaryotes. Archaeal possess information
machineries that are in essence a simplified, ancestral version of the eukaryotic machinery.
Viewing these machineries through the prism of archaea provides a unique perspective on the
fundamentally conserved molecular mechanisms of genome duplication and expression. We
have investigated these processes for many years and have in vitro systems in place for both
DNA replication and gene transcription. More recently, we have discovered that archaea of the
order Sulfolobales organize their genomes with a compartmentalized architecture –
reminiscent of that seen in higher eukaryotes. Our work has revealed a key role for a simple,
small SMC-superfamily protein, termed ClsN, in establishing and maintaining this
compartmentalized architecture. We are now ideally poised to integrate our chromosome
architecture studies with our DNA replication work, to investigate the interplay between
genome organization and the dynamic processes of DNA replication and gene expression
through combined in vitro, single-molecule and in vivo approaches. With regard to gene
expression, we have recently described an unanticipated role for ClsN in effecting an epigenetic
state in Sulfolobus. We will dissect the mechanistic basis of this state, determine how applicable
it is to other regulatory systems in Sulfolobus and investigate the mechanistic basis of the multi-
generational inheritance of ClsN-mediated conformational marks. Taken together, our work will
reveal novel insights into the core molecular biology of archaea. Additionally, due to the
relationship between archaea and eukaryotes, our work will provide a novel perspective on the
evolution and core mechanisms of orthologous processes in eukaryotes.