Susan Janicki, Ph.D.

Assistant Professor
Gene Expression and Regulation Program
215-495-6850, Office
sjanicki@wistar.org

Introduction

Many of our ideas about the inner workings of cells come from indirect experiments in fixed cells. However, it is now possible to watch living cells in action using novel imaging techniques. Molecules (proteins, RNA, and DNA) can be visualized by attaching fluorescent tags and imaging them in living cells using specialized microscopes. The Janicki laboratory is interested in developing novel technologies for such imaging and applying them to study how genes get turned on and off.

Research Summary

In response to stimuli, cells translate signaling events into interactions between regulatory factors and DNA elements resulting in changes in gene expression patterns. Chromatin organization offers an important level of control in this process, however, it is not well understood how chromatin remodeling and transcriptional and RNA processing events are coordinated in living cells.

We use a system that allows us to visualize chromatin and the RNA and protein products produced from an inducible transcription unit during activation and silencing in single living cells. Using this system, we have seen how RNA accumulates at a transcription site in relation to chromatin decondensation. In addition, HP1 is depleted and the histone H3 variant, H3.3, is incorporated into the chromatin upon activation. Visualizing these events over time in single cells has provided insight into the mechanisms through which heterochromatin is transformed during transcriptional activation.

As this system allows the temporal and spatial dynamics of a molecularly defined region of chromatin to be evaluated during transcriptional activation and silencing, it will be used to evaluate the role of chromatin structure, protein kinetics and nuclear organization in epigenetic regulation.

Selected Publications

Shav-Tal Y, Darzacq X, Shenoy SM, Fusco D, Janicki SM, Spector DL and Singer RH. Dynamics of Single mRNPs in the Nuclei of Living Cells. (2004) Science 18, 1797-1800.

Janicki SM and SpectorDL. Imaging Gene Expression in Living Cells. (2004) In: Live Cell Imaging: A Laboratory Manual Goldman RD and Spector DL, editors. Cold Spring Harbor Laboratory Press, New York.

Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH and Spector DL. From Silencing to Gene Expression: Real-Time Analysis in Single Cells. (2004) Cell 116, 683-698.

Janicki SM and Spector DL. (2003) Nuclear choreography: interpretations from living cells. Current Opinion in Cell Biology 15, 149-157.

Tsukamoto T, Hashiguchi N, Janicki SM, Tumbar T, Belmont AS, Spector DL. (2000) Visualization of gene activity in living cells. Nature Cell Biology 2, 871-878.