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The following summaries illustrate some of the research projects utilizing the BioMicro Center.

Laurie Boyer (Biology) Stem cells are essential for metazoan development and for the maintenance of tissue homeostasis in the adult organism. Embryonic stem (ES) cells can be derived from the mammalian pre-implantation embryo and have enormous therapeutic potential because they can propagated in vitro while maintaining the capacity to give rise to all cell types in the body. A major challenge in biology is to understand how these undifferentiated cells execute the diverse gene expression programs that lead to cellular specification. Chromatin organization is a fundamental mechanism used by all eukaryotes to compartmentalize the genome into functional domains in order to interpret the vast amount of genetic information encoded within the genome. The overall goal of the lab is to understand how chromatin structure influences gene expression programs and ultimately cell fate and how failure to establish proper chromatin states can contribute to disease. To address these questions, we use a combination of genomic, genetic, biochemical and cell biological tools to precisely characterize the factors involved in regulating chromatin structure, to determine how these factors are recruited to genomic sites, and to investigate how these different regulatory pathways cooperate to organize the genome. We are particularly interested in how specific chromosomal domains are assembled and propagated in ES cells, adult stem cells, and somatic cells. Discovering how gene expression programs are regulated is required to improve our understanding of development and disease, and for realizing the therapeutic potential of stem cells.

Chris Burge (Biology) We study mechanisms of posttranscriptional gene regulation using a combination of computational and experimental methods. A long-term goal is to understand the RNA splicing code: how the precise locations of exons and splice sites are identified in primary transcripts, and how this code is altered in cell- and condition-specific alternative splicing. Current efforts are focused on identifying splicing cis-regulatory elements and associated splicing factors, and understanding the context-dependent activities and functional interactions between these elements. We also study the roles that microRNAs (miRNAs) play in gene regulation, with an emphasis on determining the rules for miRNA-directed targeting of mRNAs. We are beginning to study the relationship between alternative cleavage and polyadenylation, which is commonly used to generate alternative mRNA isoforms differing in their 3' UTRs, and miRNA regulation. (expanded research description)

Sally Chisholm (Biology) The general goal of the research in my lab is to advance our understanding of microbial ecology and evolution in the oceans. In recent years we have focused our attention on a single group, the cyanobacterium Prochlorococcus, which is the smallest and most abundant microbe in ocean ecosystems — sometimes accounting for half of the total chlorophyll. This “minimal phototroph” can convert CO2, sunlight, and inorganic nutrients into a living cell with as few as 1700 genes. We have been developing Prochlorococcus, and the phage that infect them, as a model system for understanding life processes across all scales of spatial and temporal organization, from the genome to the biosphere, and from daily to evolutionary time scales. In so doing, we hope to develop a unified understanding of this one small representative of the diversity of life. (expanded research description)

Peter Dedon (expanded research description)