Robert Tjian wants to understand the molecular machinery that controls gene activity in human and animal cells. His research is helping to decipher exactly how animal cells retrieve the genetic information stored in DNA molecules during transcription – the biochemical process that leads to the production of proteins.
Tjian’s lab team has devised methods to isolate the individual cellular components that carry out transcription, and used those components to recreate the complex reaction in a test tube. This allows the team to study the detailed molecular mechanisms that direct the exquisitely sensitive process of gene expression in humans and other animals. Tjian’s team complements these in vitro investigations with studies in cells and whole organisms, such as flies and mice, in which they explore how transcription is regulated in physiological situations that require the switching on and off of specific genes, such as cell growth, development, and differentiation.
In recent years, much of Tjian’s research has focused on key transcription events in embryonic stem cells (ESCs), as well as various terminally differentiated cell types, including adipocytes (fat cells), hepatocytes (liver cells), myotubes (muscle fibers), and motor neurons. The lab has been developing single-molecule imaging technologies and exploiting powerful new microscopes that make it possible to watch the dynamic movement of transcription factors as they control gene expression, both in living cells and in “test tube” assays using purified transcription factor proteins. Observing individual transcription factor molecules allows scientists, for the first time, to measure the kinetics and three-dimensional distribution of key gene regulatory proteins as they search for and bind to target DNA sites.