RNA and protein structural biologist using crystallography and small angle scattering.
Office: BRC 468
Phone: (405) 271-8300
University of Oklahoma Health Sciences Center
975 N.E. 10th, BRC468
Oklahoma City, OK 73104
PhD, Oregon State University, 1997
Post-doc, HHMI/Univeristy of Oregon 2003
Research Associate, University of Oregon 2006
Structural biology of messenger RNA editing in the mitochondria of trypanosome
Uridine (U) insertion/deletion editing in trypanosomes is an extensive post-transcriptional process that corrects the coding sequence of most mitochondrial mRNAs. This editing is required for the subsequent expression of several mitochondrial proteins. The number of Us that are inserted far exceeds that number that is deleted; there is a net increase in the number of codons after editing. An enzyme cascade does the editing in the mitochondrion. The editing reactions are directed by hundreds of different guide RNAs. Each guide RNA has the sequence complement of a fragment of the final edited mRNA sequence. Consequently, much of the genetic information for the final RNA transcript comes from both its corresponding gene and the genes for the set of guide RNAs that direct its editing. In other words, the genetic information flows from DNA to RNA along multiple parallel pathways. This is an interesting variation of the central paradigm of molecular biology where information flows along one pathway from DNA→RNA→protein. The evolutionary basis for such a complex and expensive system of information flow is still unclear.
Our goal is to obtain a rigorous description of the structural biology of this type of RNA editing to improve our understanding of its evolutionary basis, clarify the relationship between this type of RNA editing and other types of RNA editing, and provide a structural basis of the design of better drugs to fight infections with trypanosomes which threaten 600 million people worldwide. We are particularly interested in developing drugs that target the RNA of this system.
We have also determined the crystal structures of twelve protein-drug complexes relevant to influenza and several cancers in collaboration with colleagues at OUSHC (with Drs Gillian Air, Marie Hanigan, Jie Wu, and C. V. Rao), one crystal structure of an unusual RNA with colleagues at the University of Oklahoma in Norman (with Dr. Susan Schroeder), and two forms of a glycoprotein by small-angle X-ray scattering with Dr. Chris West at OUHSC. We have also done molecular modeling of cell death-related proteins to plan and interpret biochemical experiments (Dr. Jialing Lin). Find these publications via the links to PubMed and Google Scholar.
For several years, we have been using Python programming for the parts of our research (cutting edge structure determination methods and molecular graphics) for which there are no existing software solutions (Mooers 2016a). We are also developing tools to ease the use of structural biology software like PyMOL by both beginning and expert users (Mooers 2016b, 2019, 2020, 2021; Mooers and Brown 2021). Visit our GitHub site for more information and computer code. Dr. Mooers also uses Python in several ways to help his students learn more deeply about molecular structure. In addition, he hosts -- in collaboration with Drs Giles, Hays, Mather, and Wu -- a Data Science Workshop (formerly the Python Workshop) that meets every third Thursday of each month at noon online during the pandemic. This workshop provides a forum for local scientists at all levels to exchange knowledge about how they use scientific computing in their research. The talks are recorded. Videos of past talks can be found online. Anyone can volunteer to make a presentation. About half of the talks have been made by graduate students. If you are interested in giving a talk or having your name added to the mailing list for this group, please contact Dr. Mooers.
Dr Mooers also directs a service lab called the Laboratory of Biomolecular Structure and Function (LBSF). This facility provides instruments and expertise to help researchers incorporate structural biology into their research programs. We also facilitate access to national synchrotron radiation facilities. We have particularly strong ties with SSRL (which is run by Stanford University for the DOE) for the purpose of collecting diffraction, small-angle X-ray scattering, and cryo-EM data. Dr Mooers is an active member of the SSRL Users Executive Committee and has been a user of SSRL for 22 years. The LBSF is part of the VPR's suite of core labs. This facility is also part of the Biomolecular Structure Core (BSC) of the Oklahoma COBRE in Structural Biology (OCSB, PI: Ann West, OU-Norman). The BSC has a branch on the OU-Norman campus that is known as the BSC-Norman. The Norman facility has complementary instruments. Dr. Mooers serves as the academic director of the BSC. Please contact Dr. Mooers if you would like to add structural biology to your research program.
(lab member, rotation student, *corresponding author, ^co-corresponding author, pdb codes from structures determined in my lab):
*Wu, J., Mooers, B. and Subbiah, V. (2021) Drug-adapted RET mutations. Research Outreach. 126, 78-81.
Pujari, N., Saundh, S. L., Acquah, F. A., Mooers, B. H. M., Ferre-D'Amare, A. R., and *Leung, A. K.-W. (2021). Engineering crystal packing in RNA structures I: Past and future. Crystals. 11(8), 952. (15 Aug 2021) (peer-reviewed review article). PMID: 34745656 PubMed Central PMCID: PMC8570644
Thein, K.Z., Velcheti, V., Mooers, B. H. M., Wu, J., and *Subbiah, V. (2021) Precision therapy for RET-altered cancers with RET inhibitors. Trends in Cancer. Aug 11:S2405-8033(21)00148-5. doi: 10.1016/j.trecan.2021.07.003. PMID: 34391699
*Mooers, B.H.M. (2021). Modernizing computing by structural biologists with Jupyter and Colab. Proc. of the 20th Python in Science Conf. (SCIPY 2021). p. 14-22.
Acquah, F. A., Paramel, M., Kuta, A., Hussaini, S. R., Wallace, D. R., *Mooers, B. H. M. (2021). Simulations of promising indolizidine – α6-β2 nicotinic acetylcholine receptor complexes. Int. J. Mol. Sci. 22(15): 7934. doi: 10.3390/ijms22157934. PMID :34360698, PubMed Central PMCID: PMC8347036.
Shen, T., Hu, X.+, Liu, X., Subbiah, V., Mooers, B. H. M., *Wu, J. (2021). The L730V/I RET roof mutations display different activities towards pralsetinib and selpercatinib. NPJ Precision Oncology 5:48. doi: 10.1038/s41698-021-00188-x. PubMed PMID: 34099825, PubMed Central PMCID: PMC8184971.
Subbiah, V. , Shen, T. , Tetzlaff, M. , Weissferdt, A., Byers, L. A., Cascone, T. , Behrang, A. Meric Bernstam, Mooers, B. H. M., Rothenberg, S. M. Ebata, K., *Wu, J. (2021) Patient-driven discovery and post-clinical validation of NTRK3 fusion as an acquired resistance mechanism to selpercatinib in RET fusion-positive lung cancer. Annals of Oncology, Jun;32(6):817-819 32(6):817-819. doi:10.1016/j.annonc.2021.02.010. PubMed PMID: 33617938.
*Mooers, B. H. M. (2021) A PyMOL snippet library for Jupyter to boost researcher productivity. Computing in Science and Engineering. 23(2) 47-53. doi:10.1109/MCSE.2021.3059536. PubMed PMID 33967632; PubMed Central PMCID: PMC8104305.
*Mooers, B. H. M. (2021) Running CCTBX and PyMOL in the same Jupyter Notebook. Computational Crystallography Newsletter 12, 26-32.
^Subbiah, V., Shen, T., Terzyan, S. S., Liu, X. Hu, X., Patel, K. P., Hu, M., Cabanillas, M., Behrang, A., Meric-Bernstam, F., Vo, P. T .T. , ^Mooers, B. H. M., *Wu, J. (2021) Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations. Annals of Oncology, 32(2):261-268. doi:10.1016/j.annonc.2020.10.599. PubMed PMID: 33161056. PDB-ID: 7JU5, 7JU6.
*Mooers, B. H. M. and Brown, M. E. (2021) Templates for writing PyMOL scripts. Protein Sci. 30(1):262-269. doi:10.1002/pro.3997. PubMed PMID: 33179363.
Notable GitHub Repositories
Click to view interactive PDB files
- 7JU5 RET protein tyrosine kinase with pralsetinib
- 7JU6 RET protein tyrosine kinase with selpercatinib
Link to full publication list >