RESEARCH OPENINGS
As of August 2005, the lab is actively recruiting postdocs, graduate students, and undergraduates for research positions. Scientists and engineers with diverse prior training, including biology, physics, computer science, and mathematics, are all welcome for consideration. Computer programming and mathematics skills are strongly recommended. For more information please contact Prof. Chuang at chuangj@bc.edu.

Jeff has moved to Boston College. For up to date information please visit his Boston College home page .

Research Topics
Large scale DNA sequencing has ushered in a new era in biology. There are now hundreds of organisms in which nearly all the genomic sequence is known, making it possible to comprehensively analyze and compare species at their most atomistic genetic level. At the same time, massive phenotypic datasets, such as whole-genome gene expression arrays, have become increasingly available. My lab is interested in computational and mathematical approaches to analyzing such large data sources, to understand how genomes function and evolve.

1. Detecting Functional Sequences in DNA through Comparative Genomics
In a given phylogeny, comparative sequence data can be used to infer the functional sequences within genomes. Just as morphological features shared among species (e.g. all vertebrates have a spine) are likely to be important to those species, DNA sequences shared among species are likely to be functional. My current research is focused on the identification of short DNA sequences likely to regulate the transcription and/or translation of nearby genes. Most recently, I have applied comparative techniques to identify functional sites in the promoters of the Saccharomyces genus of yeasts. Such sequence comparisons can yield predictions of not only individual DNA/protein binding sites, but also broader features, such as the complexity of gene regulation and the types of genes likely to be under the strictest regulation.

2. Identification of Neutral Mutation Rates
Evaluating the functional significance of sequences that are conserved is still a major challenge. One reason for this is that neutral mutation rates, which describe the evolution of non-functional DNA, are not always known. Another direction of the lab is therefore to characterize neutral mutation rates, which can vary both within and between species. For example, one puzzle is why mutation rates are uniform in some species, such as the sensu stricto yeasts, while rates vary by location in other species, such as mouse and human. In species where the mutation rate is non-uniform, we are interested in questions such as what structural or sequence features affect mutation rates, and whether gene locations have evolved to make use of mutational heterogeneity. A related question is what DNA sequence should be considered neutral, and in particular what the effect of codon usage bias is on silent sites in genes.

3. Evolution of Transcription Factors and Their Binding Sites
Currently, only a small fraction of the binding sites for transcription factors are known, and these are mostly restricted to a few model organisms. As more transcription factor binding sites are discovered and mapped to their counterparts in other species, it will be possible to learn how transcription regulation has evolved. Such knowledge will be extremely valuable for understanding species evolution, as many of the changes leading to speciation have been speculated to occur at the level of transcription regulation. Some questions in which we are interested are: How quickly do binding sites and transcription factors change between different species? How much of this change is neutral? How much is due to selection for new regulatory behaviors? In addition to comparative genomics techniques for identifying transcription factor binding sites across species, we also use a variety of other computational methods, including those based on motif overrepresentation and gene expression patterns. The lab is also involved in a number of collaborations to experimentally test functional sequence predictions in various species, including malaria and zebrafish.

Representative Publications
Chin, C. S., Chuang, J. H., and Li, H. 2005. Genome-wide regulatory complexity in yeast promoters: separation of functional and neutral sequence. Genome Research 15: 205–213.

Chuang, J., and Li, H. 2004. Functional bias and spatial organization of genes in mutational hot and cold regions in the human genome. PLoS Biology 2: 0253–0263.

Ito, K., Chuang, J., Alvarez-Lorenzo, C., Watanabe, T., Ando, N., and Grosberg, A. Yu. 2003. Multiple point adsorption in a heteropolymer gel and the Tanaka approach to imprinting: Experiment and Theory. Progress in Polymer Science 28: 1489–1515.

Chuang, J., Kantor, Y., and Kardar, M. 2001. Anomalous dynamics of translocation. Physical Review E 65: 011802.

Chuang, J., Grosberg, A. Yu., and Kardar, M. 2001. Free energy self-averaging in protein-sized heteropolymers. Physical Review Letters 87: 078104.

Chuang, J., Grosberg, A. Yu., and Tanaka, T. 2000. Topological repulsion between polymer globules. Journal of Chemical Physics 112: 6434.

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