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Diverse cellular functions such as mitosis, cell migration, and differentiation rely on the dynamic assembly of the microtubule cytoskeleton into distinct architectures.  We combine high-resolution fluorescence-microscopy based assays with quantitative biochemical and structural methods to dissect the molecular mechanisms underlying the organization of functional micron-length scale cytoskeletal structures from the collective activity of nanometer-sized proteins.
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The Alt laboratory studies mechanisms that maintain genomic stability in mammalian cells. The programmed recombination and hypermutation events in lymphocytes and the general DNA repair mechanisms involved in these processes are a focus. The laboratory also studies mechanisms that promote and prevent oncogenic translocations.  Approaches range from molecular genetics and biochemistry to animal models.
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The Ausubel laboratory uses genetic, genomic, and chemical genetic approaches to: (1) elucidate the molecular basis of microbial pathogenesis in the bacterial pathogens Pseudomonas aeruginosa and Pseudomonas syringae and (2) identify the components of the signaling pathways involved in the host innate immune response in the plant Arabidopsis thaliana and the nematode Caenorhabditis elegans.
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In erythrocytes, Protein 4.1R is essential for membrane integrity. Deficiencies cause congenital hemolytic anemia. We have shown that there are many isoforms of P4.1R in other tissues. These participate in the mitotic apparatus, costameres, tight junctions, and adherens junctions. We are studying the structure function relationships of these isoforms. We also study the regulated pre-mRNA splicing events that govern their tissue and differentiation stage expression.
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We use the nematode C. elegans to study processes that defend against environmental, metabolic, and proteotoxic stress, and how these stress defenses influence aging. We are particularly interested in understanding mechanisms that regulate these stress defenses at the level of gene expression, and in how growth and nutrient signals influence these regulatory mechanisms
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The Blower Lab is interested in understanding both how and why RNA is targeted to microtubules during mitosis. We primarily use cell free extracts from the African clawed frog Xenopus laevis to study how RNA influences the assembly of microtubules into a dynamic bipolar spindle.
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Constance Cepko and her colleagues study the development of the central nervous system of vertebrates, with an emphasis on the development of the retina. They are also studying the mechanisms of photoreceptor degeneration, and working towards gene therapy for prevention of blindness.
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We use quantitative whole genome and proteome measures to guide computational modeling of regulatory and enzymatic networks in microbial and mammalian cells. We develop technologies based on bioinformatics, microarrays, mass-spectrometry, automation, multiplexing, microfluidics, and homologous-recombination genome engineering. We have recently used these to discover new regulatory motifs involved in cell-cycle control, stress response, and many other network components.
We are interested in understanding the molecular mechanisms that control and coordinate transcription and co-transcriptional processes, including splicing, chromatin remodeling and termination. We develop genomic approaches to study these questions, such as nascent elongating transcript sequencing (NET-seq), which provides a quantitative measure of RNA polymerase density across the genome with single nucleotide precision.
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We are investigating mechanisms underlying germline maintenance and accurate meiotic chromosome segregation at the molecular level. We are exploring meiotic chromosome dynamics, particularly, the interplay between changes in chromosome configuration/structure during meiosis, and homologous chromosome pairing, synapsis, and DNA double-strand break repair. We are also investigating the roles of histone demethylases in germline maintenance and double-strand break repair. Our studies combine genetic,...