Our Science – GRCBL Website

Gene Regulation and Chromosome Biology Laboratory

Research

The Gene Regulation and Chromosome Biology Laboratory includes research in a variety of organisms, notably bacteriophage lambda, Escherichia coli, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Caenorhabditis elegans. This research is unified by interests in chromosome dynamics (recombination, chromosome segregation, and transposable elements) and regulation (transcription, silencing, and cell cycle control).

Dr. Strathern's laboratory is focused on the mechanisms and fidelity of recombination. The investigators have identified mutations that elevate the level of aberrant genome rearrangements. Their studies also revealed that the DNA synthesis associated with recombination is of relatively low fidelity, and they have identified genes that control this fidelity. They also study the fidelity of retrotransposition.

Dr. Klar's laboratory studies the positional silencing and the site-specific recombination mechanisms that are components of cell type switching in S. pombe. Their studies have revealed several novel genes involved in establishing or maintaining epigenetic states of gene expression. They are also characterizing a strand-specific genome marking system that programs cell type switching. In addition, Dr. Klar's laboratory studies the genetic basis of human handedness.

Using plasmid segregation in bacteria as a model for how chromosomes are properly partitioned to daughter cells at each division, Dr. Austin's laboratory identified specific protein/DNA contacts required for accurate plasmid segregation and continues to focus on mechanisms of chromosome partitioning.

Dr. Court's laboratory has demonstrated that the N gene of bacteriophage lambda exhibits two different levels of regulation on lambda genes: N binds to its own mRNA and inhibits the synthesis of more N protein, and it modifies RNA polymerase so that transcription continues through termination sites into downstream genes. The laboratory staff is investigating how these two mechanisms are related and what other cellular functions contribute to these processes. Recently, they developed improved methods for gene targeting in E. coli.

Dr. Garfinkel's laboratory is elucidating the life cycle of Ty, a retrovirus-like element that provides an excellent model for the interaction between a retrotransposon and its host. Recently, their studies identified many yeast genes involved in limiting the transposition level of Ty1. The Garfinkel and Strathern laboratories have made hybrid Ty/HIV elements in which Ty replication is dependent on the reverse transcriptase (RT) of HIV-1. Such hybrids have been used to identify new drugs that inhibit HIV-1 RT.

Dr. Kashlev's laboratory, established in August 1996, is elucidating the role of RNA polymerase in transcription elongation and termination in E. coli. The lab is also carrying out an investigation of transcription elongation in yeast.

Dr. Jin's laboratory studies RNA polymerase (RNAP), RNAP-associated proteins including RapA that is a Swi2/Snf2 protein and regulation of transcription using simple model system Escherichia coli. They are studying the effects of nutrient starvation and other stress responses on the distribution of RNAP and structure of bacterial chromosome. In collaboration with several PIs in GRCBL, Dr. Jin also isolates and characterizes RNAP mutants defective in transcription fidelity. Recently, his laboratory initiated a basic research on Helicobacter pylori pathogenesis.

This page was last updated on 9/23/2008.