Overview of the Tolbert Group

Research in the Tolbert group endeavors to understand the molecular mechanisms RNA viruses use to express their genomes. Nuclear magnetic resonance (NMR) spectroscopy and other solution biophysical methods are used to determine 3D structures and physiochemical properties of viral RNA regulatory elements both free and bound to their cognate host proteins. The research in the group is highly interdisciplinary where trainees have the opportunity to gain experience in biophysical chemistry, molecular biology, computational biology, and virology. Our primary focus is to better understand how the human immunodeficiency virus (HIV), the etiological agent of AIDS, regulates RNA processing events. Towards that end, we determined the first high-resolution structure of a key HIV regulatory RNA, the Exon Splicing Silencer 3 (ESS3), and elucidated its thermodynamic binding profile to the human protein hnRNP A1. Other projects include determining the molecular mechanisms of transcriptional control of HIV latency and translational control of Enterovirus 71 (EV71), the etiological agent of Hand, Foot, and Mouth Disease.

Tolbert Research Group Site >>

Research Techniques

NMR spectroscopy, isothermal titration calorimetry, differential scanning calorimetry, protein chromatography, X-ray crystallography and molecular dynamics simulations

Group Affiliations

• The Center for AIDS Research »
• The Center for HIV RNA Studies »

Selected Publications

1. Tolbert M, Morgan CE, Pollum M, Crespo C, Li ML, Brewer G, and Tolbert BS (2017). HnRNP A1 Alters the Conformational Dynamics of a Conserved EV IRES Domain to Stimulate Viral Translation. In press JMB (2017). Selected for Featured Cover Article and expert commentary
2. Jain N, Lin HC, Morgan CE, Harris ME and Tolbert BS (2017). Rules of RNA Specificity of hnRNP A1 Revealed by Global and Quantitative Analysis of its Affinity Distribution. PNAS 114(9), 2206-2211. 
3. Jain N, Morgan CE, Rife BD, Salemi M and Tolbert BS (2-16). Solution Structure of the HIV-1 Intronic Splicing Silencer and its Interactions with the UP1 Domain of hnRNP A1. J Biol Chem 29(15), 2331-2344.
4. Morgan CE, Meagher JL, Levengood JD, Delproposto J, Rollins C, Stuckey JA and Tolbert BS, (2015) The First Crystal Structure of the UP1 Domain of hnRNP A1 Bound to RNA Reveals a New Look for an Old RNA Binding Protein. J Mol Biol, doi:10.1016/j.jmb.2015.05.009. In press.
5. Rollins C, Levengood JD, Rife BD, Salemi M, and Tolbert BS (2014). “Thermodynamic and Phylogenetic Insights into hnRNP A1 Recognition of the HIV-1 Exon Splicing Silencer 3 Element”. Biochemistry 53(13), 2172-2184.
6. Levengood JD, Tolbert M, Li ML, and Tolbert BS (2013). “High-Affinity interactions of hnRNP A1 with conserved RNA structural elements is required for translation and replication of Enterovirus 71”. RNA Biology 10(6), 1-10. Featured cover article.
7. Blakeley BD, DePorter SM, Mohan U, Burai R, Tolbert BS, and McNaughton BR (2012). “Methods for identifying and characterizing interactions involving RNA”. Tetrahedron 68, 8837-8855.
8. Feldman EA, Ni S, Sahu ID, Mishler CH, Levengood JD, Kushnir Y, McCarrick RM, Lorigan GA, Tolbert BS, Callahan SM, and Kennedy MA (2012). “Differential binding between PatS C-terminal peptide fragments and HetR from Anabaena sp. PCC 7120”. Biochemistry 51, 2436-42.
9. Levengood JD, Rollins C, Mishler CH, Johnson CA, Miner G, Rajan P, Znosko BM, and Tolbert BS (2012). “Solution structure of the HIV-1 exon splicing silencer 3”. J Mol Biol. 414, 680-98.
10. Feldmann EA, Ni S, Sahu ID, Mishler CH, Risser DD, Murakami JL, Tom SK, McCarrick RM, Lorigan GA, Tolbert BS, Callahan SM, and Kennedy MA (2011). “Evidence for direct binding between HetR from Anabaena sp. PCC 7129 and PatS-5”. Biochemistry 50, 9212-24.
11. Miyazaki Y, Irobalieva RN, Tolbert BS, Smalls-Mantey A, Iyalla K, Loeliger K, D’Souza V, Khant H, Schmid MF, Garcia EL, Telesnitsky A, Chiu W, and Summers MF (2010). “Structure of a conserved retroviral RNA packaging element by NMR spectroscopy and cryo-electron tomography”. J Mol Biol. 404, 751-772. Cover Article.
12. Tolbert BS, Miyazaki Y, Barton S, Kinde B, Stark P, Singh R, Bax A, Case D, Summers MF (2010). “Major groove width variations in RNA structures determined by NMR and impact of 13C residual chemical shift anisotropy and 1H-13C residual dipolar coupling on refinement”. J Biomol NMR, 47, 205-219.

Book Chapters

• Tolbert BS, Rollins C, Levengood JD, Luo L, and Rajan P (2013). “Probing the structural basis of retroviral RNA functions via NMR spectroscopy”. RNA Nanotechnology; ch. 8.

Group News

• January 2014 – Tolbert was featured in The Daily
• January 2014 – Tolbert was interviewed by The Plain Dealer about the amfAR grant
• January 2014 – Tolbert was one of 12 recipients to receive an amfAR grant to investigate basic molecular mechanisms of transcriptional control of HIV latency
• Fall semester 2013 – With the Center for RNA Molecular Biology at CWRU, Tolbert hosts seminar series Frontiers in Nucleic Acid Chemistry, which included lectures by Harry Noller, Tom Cech, Adrian Ferre-D’Amare and Anna M. Pyle
• April 2013 – Tolbert was awarded a CFAR Developmental grant to investigate the biophysical and biochemical control of HIV transcription
• January 2013 – Tolbert receives a Keystone Symposium Early Career Investigator Travel Award
• July 2012 – Tolbert was awarded an NIH R01 grant, Structural Biophysics of HIV Splicing
• July 2012 – Tolbert was awarded a subcontract with the NIH funded Center for HIV RNA Studies
• June 2012 – The Tolbert lab relocates to the Department of Chemistry at Case Western Reserve University