个人简介

B.A., University of Colorado, Boulder, 1992. Ph.D., Brandeis University, 1997 (Michael Rosbash). Postdoctoral: University of Colorado, 1998-2000 (Steve Schultz), 2000-01 (Tom Cech). Honors and Awards: Burroughs Wellcome Fund Fellow of the Life Sciences Research Foundation 1998-2001; Basil O’Connor Scholar 2004-06. At Oregon since 2002.

研究领域

Biochemistry/Molecular Biology/Biophysics

The primary goals of the Berglund lab are to understand the molecular basis of the human disease myotonic dystrophy (a form of muscular dystrophy) and the mechanisms regulating pre-mRNA splicing. Myotonic dystrophy is caused by the expression of a toxic RNA, which is made up of greater than 100 expanded CUG repeats. This toxic RNA functions in the cell by sequestering a RNA binding protein (muscleblind). The sequestration of muscleblind to the expanded toxic CUG repeats means muscleblind is no longer able to carry out its normal function in the cell. At least one of the functions of muscleblind is to regulate the alternative splicing of various pre-mRNAs (see figure). Without the proper regulation of alternative splicing by muscleblind, splicing defects occur and some of the symptoms of myotonic dystrophy can be directly correlated to these mis-splicing events. To study the structure and function of the toxic CUG repeats and muscleblind we are using a combination of biochemical, structural biology and bioinformatic methods. The identification of RNA motifs through which muscleblind regulates splicing is a goal within our lab. Interestingly, muscleblind can function either to positively or negatively regulate the splicing of an exon and we would like to understand the mechanisms through which muscleblind makes this choice for the many different exons it regulates. We have also begun to study small molecules that bind the toxic CUG repeats and release muscleblind from sequestration, so this protein can once again properly regulate splicing. We are collaborating with Professor Michael Haley (also a member of the Chemistry department at the University of Oregon) to synthesize molecules that bind the expanded CUG repeats. We are also interested in identifying and studying all RNA motifs and splicing factors that regulate pre-mRNA splicing because it is clear that splicing plays an important role in expanding the diversity of human genes and incorrect splicing causes a variety of diseases. Most human genes are alternative spliced and many of these splicing events are tissue specific or developmentally controlled. Bioinformatic tools have been used to identify novel RNA motifs involved in splicing and we are currently determining how these motifs and their associated proteins function in a combinatorial manner to regulate splicing. A new area of research in the lab is the use of RNA in the synthesis of nanomaterials. We are exploring the ability of RNA to control the shape and size of nanoparticle growth. This is a collaborative project with Professor Jim Hutchison (also a member of the Chemistry department at the University of Oregon).

近期论文

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Mooers, B.H.M., Logue, J.S., Berglund, J.A. 2005. The structural basis of myotonic dystrophy from the crystal structure of CUG repeats. Proc Natl Acad Sci USA. 102(46):16626-31. Cass, D., Berglund J.A. 2006. The SF3b155 N-terminal Domain is a scaffold important for splicing. Biochemistry 45 (33); 10092-10101. Garrey S. M., Voelker R., Berglund, J.A. 2006. An extended RNA binding site for the yeast branchpoint binding protein and the role of its Zn knuckle domains in RNA binding. J Biol Chem. 281(37): 27443-53. Voelker, R., Berglund, J.A. 2007. A Comprehensive Computational Characterization of Conserved Mammalian Intronic Sequences Reveals Conserved Motifs Associated with Constitutive and Alternative Splicing. Genome Research Jul;17(7):1023-33. Warf, M.B., Berglund, J.A. 2007. MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its intronic pre-mRNA target in cardiac troponin T. RNA Dec;13(12):2238-51. Garrey, S.M., Cass, D.M., Wandler, A. M., Berglund, J.A. 2008. Transposition of two amino acids changes a promiscuous RNA binding protein into a sequence specific RNA binding protein. RNA Jan;14(1):78-88. Henscheid, K.L., Voelker, R.B., Berglund, J.A. 2008. Alternative modes of RNA binding by U2AF65 at the polypyrimidine tract. Biochemistry 47(1): 449-59. Murray, J.L., Voelker, R.B., Henscheid, K.L., Warf, M.B., Berglund, J.A. 2008. Identification of motifs that function in the splicing of non-canonical introns. Genome Biol. June 12: 9(6): R97. Epub 2008 June 12. Goers, E.S., Voelker, R.B., Gates, D.P., Berglund, J.A., 2008. RNA binding specificity of Drosophila Muscleblind. Biochemistry 47(27): 7284-7294.