David M. Gilbert
Chromosomes are central to cellular identity, development and heredity, yet we still have a primitive understanding of how they influence cellular and organismal phenotypes. With the exception of highly localized functions such as transcription of specific genes, involving a tiny fraction of the genomic space, the field of Chromosome Biology has remained largely a descriptive science. Modern innovative genomics and imaging applications are beginning to describe the structure of chromosomes, but cannot probe mechanism or biological significance. The broader challenge of integrating genotype with phenotype will require an understanding of previously impenetrable chromosomal mechanisms; non-genic phenomena such as higher order genome organization, replication-timing, transvection, random mono-allelic expression, chromosomally-associated lncRNAs, transposable element activity and the dark matter of chromosomes, are all enigmatic sources of phenotypic diversity. Resolving these mysteries has been difficult with traditional scientific approaches. Members of the Gilbert lab are motivated by the belief that studying replication will reveal mechanisms that link many or perhaps all of these myriad chromosomal phenomena. We also believe that there could not be a more exciting time to be doing chromosome biology; it is still full of fundamental mysteries but recent technologies have made investigation of these mysteries tractable. To achieve these goals, our research environment encourages independent pursuit of creative new ideas that challenge paradigms and push the boundaries of modern molecular and cellular biology. We promote cross-disciplinary collaboration, networking and provide mentorship focused on personalized career development.
Our focus is the regulation of where and when DNA replication initiates and the phenotypic consequences of initiating at the wrong place or time. DNA replication is fundamental to life science yet these rudimentary questions remain amongst the greatest unanswered mysteries in molecular biology. DNA replication provides an excellent forum in which to study chromosome structure and function. Chromatin is assembled at the replication fork and different types of chromatin are assembled at different times during S phase. Thus, replication presents a window of opportunity for us, as scientists, to observe the process by which entire chromosomes are dismantled and re-assembled. A combination of cytological and genomic studies have demonstrated that 3D structural units of chromosomes are the units of DNA replication control, each 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 animal development and recurrent changes are found as signatures of specific diseases and cancer clones. We would like to understand what regulates where and when replication begins, 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, particularly cancers, where replication timing alterations can disrupt the epigenome, transcription and genome integrity. Read more
Research Highlights
- Cold Spring Harbor Epigenetics and Chromatin 2022: ERCEs are replication enhancers
- The Jungle Book Project
- Encyclopedia of DNA Elements
- Stem Cell Surprise
- Stem Cell Surprise Video
- DNA as you have never seen it before
- A New Study Just Solved One of The Greatest Mysteries of DNA Replication
- Cold Spring Harbor Symposium 2018
- Cold Spring Harbor Symposium 2017
- Cold Spring Harbor Symposium 2015
- DCMB Seminar 2015
- Cold Spring Harbor Symposium 2013
- Interview with Dr. Gilbert 2012
- Cold Spring Harbor Symposium 2010
- In Search of lost timing 2010
About David M. Gilbert
Education:
- Ph.D. Genetics, 1989, Stanford University
- B.A. Biochemistry, Cell Biology and Philosophy, 1982, UC San Diego
Postdoctoral Fellows:
- Faculté de Médecine, FRANCE
- Roche Institute of Molecular Biology
Awards:
- 2002 SUNY Upstate President’s Award for Excellence in Research by a Young Investigator
- 2004 NIH Career Enhancement (K18) Award for Stem Cell Research
- 2006-2020 J. H. Taylor Distinguished Professor of Molecular Biology
- 2008 – Elected as Fellow, American Association for the Advancement of Science
- 2015 – 2018 FSU Biology Pfeiffer Endowed Professorship for Cancer Research
- 2015 Florida State University Distinguished Professor Award
- 2016 Florida State University Graduate Mentorship Award
Interests:
- Structure and replication of chromosomes in stem cells and cancer
Fundings:
Address information:
Email: gilbert@sdbri.org
DNA DAVE’s Blog Site:
• The Voyage is the Destination
DNA DAVE LLC: Scientific Writing, Editing and More!:
The Gilbert Laboratory 