HomeResearchIntramural ResearchResearch Branches at NHGRIGenome Technology Branch Margulies Lab

Elliott Margulies, Ph.D. Investigator Genome Informatics Section B.S. Rutgers University, 1995 Ph.D. University of Michigan Medical School, 2001 (301) 594-9210 (301) 480-3520 elliott@nhgri.nih.gov 5625 Fishers Ln Room 5N-01N, MSC 9400 Rockville, MD 20892-9400 Selected Publications

Dr. Margulies develops bioinformatic approaches that utilize ultra-high-throughput DNA sequencing technologies to sequence and characterize genomes. His group combines the application of these new sequencing technologies with bioinformatic studies that aim to examine a variety of scientific questions, ranging from those aimed at better understanding basic genome biology to those helping to address important clinical problems. In aggregate, these efforts seek to enhance our ability to decipher the information encoded within genomes.

Dr. Margulies' group combines experimental and bioinformatic approaches to identify and characterize the genetic information that confers biological function. Indeed, many of the functional elements encoded within the human genome are yet to be discovered; however, uncovering how basic biological phenomena are encoded within genomes is essential for understanding human development and disease. Many of the projects being pursued in Dr. Margulies' laboratory involve high-throughput experiments that generate large amounts of data; such data are then analyzed computationally to quantify gene expression, DNA-protein interactions, and genomic variation.

Another component of Dr. Margulies' research program involves developing and using analytical methods for detecting evolutionarily constrained sequences and determining their functional significance. The conservation of such sequences over millions of years of evolution is strong evidence that they play important biological roles, such as coding for critical genes or functioning as regulatory elements.

Toward that end, Dr. Margulies is developing new methods for detecting cross-species conservation that take into account the important role of the chromatin structure in genome function. Two approaches are currently being pursued. The first involves an in-depth analysis of the "molecular topograph" of DNA. Recently, it was shown that different DNA sequence patterns can produce similar three-dimensional structures.

Using this information, Dr. Margulies is analyzing the structural similarity of orthologous genomic regions from different species to establish the role of DNA topography in genome function. The second approach involves evaluating functional conservation across different species. Using multi-species sequence alignments as a framework, specific functions (e.g., the binding of certain proteins) that occur at the same relative position in multiple species can be identified. In some cases, the identified sequences are quite different between species, yet they seem to confer a similar function. By analyzing these sequences more carefully, Dr. Margulies hopes to uncover how the genome can encode function in ways other than through its primary sequence.

In addition to computational projects, Dr. Margulies is developing high-throughput methods to assay large regions of the genome for transcriptional regulatory activity. For example, he recently developed a new approach that couples in vitro cell-based transfections with cell sorting to identify candidate enhancer sequences; he hopes to expand the use of these methods to allow an entire genome to be assayed at once. By coupling the data generated in the laboratory with various computational analyses, his group hopes to establish multidisciplinary approaches for studying genome function.

Finally, Dr. Margulies' laboratory has been instrumental in implementing "next-generation" DNA sequencing technologies at NHGRI. These new platforms can generate significantly larger amounts of sequence data at a fraction of the cost and time compared to traditional methods. His group has been working closely with the NIH Intramural Sequencing Center (NISC) and other NHGRI Investigators to apply these new sequencing technologies to a variety of biomedical research projects. Other applications are also being pursued in Dr. Margulies' laboratory, including new approaches for whole-genome sequencing and the sequencing of unknown microbial pathogens.

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Last Updated: April 1, 2009