Biological Science Faculty Member
Dr. David M. Gilbert
Ph.D., Stanford University, 1989
Graduate Faculty Status
Research and Professional Interests:
Our overall goal is to understand how mammalian chromosomes are organized within the nucleus to carry out their various functions. DNA replication provides an excellent forum with which to study chromosome structure and function because the entire strcuture of the chromosome, not just the DNA, must be completely dismantled and 2 copies re-assembled during replication. Structural and functional units of chromosomes replicate coordinately, often through the synchronous firing of clusters of replication origins that encompass domains of approximately 1Mb. Each of these replication domains is programmed to replicate at a specific time during S-phase. In general, transcriptionally active (euchromatin) domains replicate early in S-phase and transcriptionally silent (heterochromatin) domains replicate late. Programmed changes in replication timing accompany key stages of metazoan development and are often coupled to changes in gene expression. These findings suggest that structural, functional, and replication domains share topographical boundaries and represent basic units of chromosome organization. In 2019 we discovered the the DNA elements that control the replication process and we discovered that these same elements also control transcription and 3D organization of chromatin. We are currently dissecting these elements to understand how they function and whether their various activities can be uncoupled. We are also examining how replication is coordinated with transcription and architecture in 3 dimensions, that is, how distant replication origins fire simultaneously and how cells dismantle and re-assemble chromosome structure and function to replicate. Ultimately, we would like to understand how developmental cues communicate with the cell-cycle machinery to elicit changes in the program for replication and how that program is disrupted in disease.