Research Interests   Functional genomics, analysis of gene expression patterns, microarray applications.

My laboratory uses and develops tools for functional genomics with the goal of better understanding the molecular principles behind complex biological phenomena. Parallel probing of multiple structural and regulatory sequences representing almost entire genomes has opened enormous opportunities for genetic screening and molecular phenotypic analysis. It also presents us with new challenges that were not common in the field of molecular biology such as interpretation of data sets of high dimensionality, statistical inference and multi-parametric modeling and optimization. In our work on Escherichia coli and Saccaromyces cerevisiae we design, produce and use whole genome DNA microarrays to advance research on these organisms in several directions:

Development of microarray technologies.
We have demonstrated that it is possible to trace the progression of bacterial replication fork in vivo in real time at about 1 kb resolution using DNA microarrays, as well as to localize DNA deletions and amplifications. In my laboratory we are expanding the high-resolution potential of microarray analysis by developing parallel transposon positioning technology in conjunction with saturation genome-wide mutagenesis.

Transcriptional dynamics of "elementary" transitions.
Microbial cells grow and divide according to the internal genetic programs and external cues. External cues invariably trigger transcriptional responses by the cell. We have demonstrated that global analysis of mRNA levels can be very useful in delineating such responses by determining transient and steady-state changes in transcript abundances. However, even for well-established processes the exact sequence of transcriptional events of the corresponding transcriptional program is not known. In my group we are attempting a temporal sequencing of such events in response to elementary stimuli and we expect that such analysis will offer insights into the basis of regulation, pathway connectivity and intracellular flow of information.

Bacterial chromosome dynamics and organization.
Global analysis of transcript abundances revealed spatial patterns of transcriptional activity in the E. coli chromosome. Our work has illuminated the complexity in organization of the bacterial chromosome and effectively shifted our view of the chromosome as an amorphous storage of genetic information to the view of the chromosome as an organelle-like constituent of the cell. Our studies aim at understanding global chromosomal properties and their relation to the chromosome function in the processes of transcription, replication and recombination and in determining chromosomal basis of genetic plasticity. In our analysis of the chromosomal organization and function we employ tools of genomics, genetics, signal processing and statistics.

Transcriptional networks and the data analysis.
We use growing information about transcriptional activity of the E. coli and S. cerevisiae living genomes to do comprehensive decoding of transcriptional regulatory networks in cells of those organisms. We rely on multiple biological replicates, high experimental dimensionality, and various integrated sampling techniques to provide high quality dynamic picture of the transcriptional regulation and connectivity in microbial cells.

Brian J. Peter, Javier Arsuaga, Adam M. Breier, Arkady B. Khodursky, Patrick O. Brown, Nicholas R. Cozzarelli. “Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli.” Genome Biology 5(11), R87, 1-16, 2004

Kyeong S. Jeong, Jaeyong Ahn and Arkady B. Khodursky. “Spatial patterns of transcriptional activity in the chromosome of Escherichia coli.” Genome Biology 5(11), R86, 1-10, 2004.

Shaobin Zhong, Arkady B. Khodursky, Daniel E. Dykhuizen and Anthony M. Dean. Evolutionary genomics of ecological specialization. Submitted to Proc. Natl. Acad. Sci. USA, 101(32):11719-24, 2004.

Arkady B. Khodursky and Jonathan A. Bernstein. Life after transcription Revisiting the fate of messenger RNA. Trends in Genetics, 19(3), 113-5, 2003.

Arkady B. Khodursky, Jonathan A. Bernstein, Brian Peter, Virgil Rhodius, Volker Wendisch, Dan Zimmer. Escherichia coli spotted double strand DNA microarrays: RNA extraction, labeling, hybridization, quality control and data management. Methods in Molecular Biology, v.224, 61-78, 2003.

Travis J. Tani, Arkady B. Khodursky, Robert M. Blumenthal, Patrick O. Brown, Rowena G. Matthews. Adaptation to famine: a family of stationary-phase genes revealed by microarray analysis. Proc. Natl. Acad. Sci. USA, 99, 13471-6, 2002.

Jonathan A. Bernstein, Arkady B. Khodursky, Pei-Hsun Lin, Sue Lin-Chao and Stanley N. Cohen. Global Analysis of mRNA Decay and Abundance in E.coli at Single Gene Resolution using Two-Color Fluorescent DNA Microarrays, Proc. Natl. Acad. Sci. USA, 99, 9697-702, 2002.

Justin Courcelle, Arkady Khodursky, Brian Peter, Patrick O. Brown, and Philip Hanawalt. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics, 158(1), 41-64, 2001.

Volker F. Wendisch, Daniel Zimmer, Arkady B. Khodursky, Brian J. Peter, and Sydney Kustu. Isolation of Escherichia coli mRNA and comparison of expresson using mRNA and total RNA on DNA microarrays, Anal. Biochem. 290, 205-213, 2001.

Daniel P. Zimmer, Eric Soupene, Haidy L. Lee, Volker F. Wendisch, Arkady B. Khodursky, Brian J. Peter, Robert A. Bender, and Sydney Kustu. NtrC-controlled genes of Escherichia coli: scavenging as a defense against nitrogen limitation, Proc. Natl. Acad. Sci. USA, 97(26), 14674-9, 2000.

Arkady B. Khodursky, Brian J. Peter, David Botstein, Patrick O. Brown, and Charles Yanofsky. DNA microarray analysis of physiological conditions and genetic changes that affect tryptophan metabolism in Escherichia coli. Proc. Natl. Acad. Sci. USA, 97, 12170-12175, 2000.

Arkady B. Khodursky, Brian J. Peter, Molly B. Schmid, Joseph DeRisi, David Botstein, Patrick O. Brown, and Nicholas R. Cozzarelli. Analysis of topoisomerase function in bacterial replication fork movement: Use of DNA microarrays. Proc. Natl. Acad. Sci. USA, 97, 9419-9424, 2000.