Professor Phone: 406-243-6393 Office: CHCB 202 Email: stephen.lodmell@umontana.edu

Current Office Hours

Office Hours :

M, T, W 9-10

and by appointment

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Background

The overall research focus of my group is viral RNA structure and function, including RNA-protein, RNA-RNA, and RNA-small molecule interactions.  Our study systems include HIV-1, HIV-2, and Rift Valley fever virus.  Specifically, we investigate the roles of RNA structural motifs within the viral genomes and mRNAs in the processes of viral packaging, translation, and splicing.  Inhibition of any of these essential processes represents a potential antiviral therapeutic approach.

Education

B.S. Chemistry, University of Montana 1985 M.S. Biochemistry, University of Montana, 1991 Ph.D. Biology, Brown University, 1996

Courses Taught

BIOC561 RNA Structure and Function (every semester)

BIOC482 Biochemistry (Spring 09)

BIOC584 Nucleic Acids Biochemistry (Fall 09)

BIOC380 Fundamentals of Biochemistry (Fall 2010)

MICB420 Virology (occasionally)

BIOC481 Biochemistry (occasionally)

Research Interests

My research interests lie in the mechanisms of molecular recognition between biological macromolecules. In particular, I am interested in RNA-RNA and RNA-protein interactions in two different systems: those that are essential for specific replicative functions in retroviruses, and those that are important for ribosome function.  The genomic RNA of HIV-2 contains not only coding information for proteins, but also functional signals for transactivation, dimerization, encapsidation, splicing, and poly A addition. Thus one major effort in my laboratory is to construct detailed secondary and tertiary structure maps of HIV-2 RNA functional motifs using solution structure probing techniques.  The ultimate goal of this line of research is to understand the structure and functions of this crucial portion of the HIV genome in sufficient detail to be able to target it for antiretroviral chemotherapies.  The other major thrust in our laboratory is using novel tethered chemical nucleases and crosslinking agents to investigate structural dynamics of the ribosome during protein synthesis.  The high resolution crystal structures of the ribosome has recently been published which has given us a good look at the static structure of these universal subcellular particles.  However, we know that the ribosome is quite dynamic during the processive catalysis of peptide bond formation, thus our efforts are focused on elucidating the important conformational changes that occur in the ribosome during protein synthesis.

Field of Study

Viral RNA structure and function

Selected Publications

Wright BE, Schmidt KH, Hunt AT, Lodmell JS, Minnick MF, Reschke DK (2011) The roles of transcription and genotoxins underlying p53 mutagenesis in vivo. Carcinogenesis. (in press; DOI: 10.1093/carcin/bgr177).

Ellenbecker MB, Sears LM, Li P, Lanchy JM, Lodmell JS (2011) Identification and Characterization of Rift Valley Fever Virus Nucleocapsid Protein-RNA Binding Motifs. Submitted.

Strong CL, Lanchy JM, Lodmell JS. Viral SELEX reveals individual and cooperative roles of the C-box and G-box in HIV-2 replication. RNA. 2011;17(7):1307-20. PMCID: 3138567.

Strong CL, Lanchy JM, Dieng-Sarr A, Kanki PJ, Lodmell JS. A 5'UTR-Spliced mRNA Isoform Is Specialized for Enhanced HIV-2 gag Translation. J Mol Biol. 2009;391(2):426-37. PMCID: PMC2750851.

Baig TT, Lanchy JM, Lodmell JS. Randomization and in vivo selection reveal a GGRG motif essential for packaging human immunodeficiency virus type 2 RNA. J Virol. 2009;83(2):802-10. PMCID: PMC2612376.

Baig TT, Strong CL, Lodmell JS, Lanchy JM. Regulation of primate lentiviral RNA dimerization by structural entrapment. Retrovirology. 2008;5:65. PMCID: PMC2494553.

Lanchy JM, Lodmell JS. An extended stem-loop 1 is necessary for human immunodeficiency virus type 2 replication and affects genomic RNA encapsidation. J Virol. 2007;81(7):3285-92. PMCID: PMC1866085.

Fabbretti A, Pon CL, Hennelly SP, Hill WE, Lodmell JS, Gualerzi CO. The real-time path of translation factor IF3 onto and off the ribosome. Mol Cell. 2007;25(2):285-96.

Baig TT, Lanchy JM, Lodmell JS. HIV-2 RNA dimerization is regulated by intramolecular interactions in vitro. RNA. 2007;13(8):1341-54. PMCID: PMC1924897.

Criswell D, Tobiason VL, Lodmell JS, Samuels DS. Mutations conferring aminoglycoside and spectinomycin resistance in Borrelia burgdorferi. Antimicrob Agents Chemother. 2006;50(2):445-52. PMCID: PMC1366916.

Knight W, Hill W, Lodmell JS. Ribosome builder: a software project to simulate the ribosome. Comput Biol Chem. 2005;29(2):163-74.

Hennelly SP, Antoun A, Ehrenberg M, Gualerzi CO, Knight W, Lodmell JS, et al. A time-resolved investigation of ribosomal subunit association. J Mol Biol. 2005;346(5):1243-58.

Bowen WS, Van Dyke N, Murgola EJ, Lodmell JS, Hill WE. Interaction of thiostrepton and elongation factor-G with the ribosomal protein L11-binding domain. J Biol Chem. 2005;280(4):2934-43.

RNASocietyNews. Annual RNA/Scaringe Award Presented to Stefano Marzi. RNA. 2004;10(8):1036.

Lanchy JM, Szafran QN, Lodmell JS. Splicing affects presentation of RNA dimerization signals in HIV-2 in vitro. Nucleic Acids Res. 2004;32(15):4585-95. PMCID: PMC516069.

Brandi L, Marzi S, Fabbretti A, Fleischer C, Hill WE, Gualerzi CO, et al. The translation initiation functions of IF2: targets for thiostrepton inhibition. J Mol Biol. 2004;335(4):881-94.

Marzi S, Knight W, Brandi L, Caserta E, Soboleva N, Hill WE, et al. Ribosomal localization of translation initiation factor IF2. RNA. 2003;9(8):958-69. PMCID: PMC1370462.

Lodmell JS, Hennelly SP. Conformational dynamics within the ribosome. In: Lapointe J, Brakier-Gingras L, editors. Translation Mechanisms. Georgetown, TX USA: Kluwer Academic/ Plenum Publishers; 2003. p. 264-79.

Lanchy JM, Rentz CA, Ivanovitch JD, Lodmell JS. Elements located upstream and downstream of the major splice donor site influence the ability of HIV-2 leader RNA to dimerize in vitro. Biochemistry. 2003;42(9):2634-42. PMCID: PMC1473984.

Lanchy JM, Ivanovitch JD, Lodmell JS. A structural linkage between the dimerization and encapsidation signals in HIV-2 leader RNA. RNA. 2003;9(8):1007-18. PMCID: PMC1370466.

Deer EL, Douk B, Lanchy JM, Lodmell JS. Elucidation and characterization of oligonucleotide-accessible sites on HIV-2 leader region RNA. Antisense Nucleic Acid Drug Dev. 2003;13(1):45-55. PMCID: PMC1403296.

Lanchy JM, Lodmell JS. Alternate usage of two dimerization initiation sites in HIV-2 viral RNA in vitro. J Mol Biol. 2002;319(3):637-48. PMCID: PMC1451413.

Lodmell JS, Ehresmann C, Ehresmann B, Marquet R. Structure and dimerization of HIV-1 kissing loop aptamers. J Mol Biol. 2001;311(3):475-90.

Jossinet F, Lodmell JS, Ehresmann C, Ehresmann B, Marquet R. Identification of the in vitro HIV-2/SIV RNA dimerization site reveals striking differences with HIV-1. J Biol Chem. 2001;276(8):5598-604.

Bowen WS, Hill WE, Lodmell JS. Comparison of rRNA cleavage by complementary 1,10-phenanthroline-Cu(II)- and EDTA-Fe(II)-derivatized oligonucleotides. Methods. 2001;25(3):344-50.

Lodmell JS, Ehresmann C, Ehresmann B, Marquet R. Convergence of natural and artificial evolution on an RNA loop-loop interaction: the HIV-1 dimerization initiation site. RNA. 2000;6(9):1267-76. PMCID: PMC1370000.

Jossinet F, Paillart JC, Westhof E, Hermann T, Skripkin E, Lodmell JS, et al. Dimerization of HIV-1 genomic RNA of subtypes A and B: RNA loop structure and magnesium binding. RNA. 1999;5(9):1222-34. PMCID: PMC1369845.

Lodmell JS, Paillart JC, Mignot D, Ehresmann B, Ehresmann C, Marquet R. Oligonucleotide-mediated inhibition of genomic RNA dimerization of HIV-1 strains MAL and LAI: a comparative analysis. Antisense Nucleic Acid Drug Dev. 1998;8(6):517-29.

Gregory ST, Brunelli CA, Lodmell JS, O'Connor M, Dahlberg AE. Genetic selection of rRNA mutations. Methods Mol Biol. 1998;77:271-81.

Lodmell JS, Dahlberg AE. A conformational switch in Escherichia coli 16S ribosomal RNA during decoding of messenger RNA. Science. 1997;277(5330):1262-7.

O'Connor M, Brunelli CA, Firpo MA, Gregory ST, Lieberman KR, Lodmell JS, et al. Genetic probes of ribosomal RNA function. Biochem Cell Biol. 1995;73(11-12):859-68.

Lodmell JS, Gutell RR, Dahlberg AE. Genetic and comparative analyses reveal an alternative secondary structure in the region of nt 912 of Escherichia coli 16S rRNA. Proc Natl Acad Sci U S A. 1995;92(23):10555-9. PMCID: PMC40650.

Lodmell JS, Tapprich WE, Hill WE. Evidence for a conformational change in the exit site of the Escherichia coli ribosome upon tRNA binding. Biochemistry. 1993;32(15):4067-72.

Marconi RT, Lodmell JS, Hill WE. Identification of a rRNA/chloramphenicol interaction site within the peptidyltransferase center of the 50 S subunit of the Escherichia coli ribosome. J Biol Chem. 1990;265(14):7894-9.