Timothy Christensen

Education

• B.S., University of Utah, 1996
• Ph.D., Cornell University, 2002

Research Interests

Using the model organism Drosophila melanogaster we study the intersection of DNA replication and heterochromatic silencing. DNA replication is an essential process that must be carried out with high fidelity. Dire consequences result when this process fails to faithfully duplicate DNA both with respect to sequence and at the right time during the cell cycle.

The suite of proteins involved in DNA replication do not operate on a naked DNA substrate but rather must perform in the context of the higher order structure of chromatin. Re-establishment of chromatin states during or right after DNA replication is critical for the organism. High fidelity of this process ensures that the transcriptional states of numerous genes are maintained. In addition the modulation of these states can contribute to the differentiation and development of tissues within the body.

What is becoming increasingly apparent is the processes of DNA replication and establishment of chromatin structure are linked. Moreover this linkage is likely the result of multiple functions for DNA replication proteins. Proteins such as the Origin recognition complex (ORC), mini-chromosome maintenance proteins (MCMs), and members of the DNA elongation machinery have all been implicated in the establishment of chromatin states during and after DNA replication.

In our lab we explore these linkages between DNA replication and chromatin through the use of a wide variety of techniques. We employ classical genetic approaches to understand the impact of mutations in selected genes on the establishment of heterochromatin (a repressive tightly packaged form of chromatin), DNA replication, and development. We seek to understand the phenotypes observed through the use of transgenic flies and high resolution microscopy. In addition to classical genetic approaches we seek to understand the function of selected proteins through identification of interacting proteins. To accomplish this we use two-hybrid analysis, immuno-precipitation, and affinity chromatography techniques.