Blaine H.M. Mooers, PhD

Associate Professor
Director of the Laboratory of Biomolecular Structure and Function

Academic Director of the  OCSB Biomolecular Structure Core

Member and past Chair of the Stanford Synchrotron Radiation Lightsource Users Executive Committee

Member of the Stephenson Cancer Center

 


RNA and protein structural biologist using crystallography and small angle scattering. 


Contact Information:

Office: BRC 468

Phone: (405) 271-8300

Mailing Address:

University of Oklahoma Health Sciences Center

975 N.E. 10th, BRC468
Oklahoma City, OK  73104

blaine-mooers@ouhsc.edu


Education:

PhD, Oregon State University, 1997

Post-doc, HHMI/Univeristy of Oregon 2003

Research Associate, University of Oregon 2006


Research Interests:

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 are 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 a number 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 that 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 to 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 nine protein-drug complexes relavant to influenza and several cancers in collaboration with collegues at OUSHC (with Drs Gillian Air, Marie Hanigan, and Jie Wu), one crystal structure of an unusal 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 realted proteins to plan and interpret biochemical experiments (Dr. Jialing Lin). Find these publications via the links to PubMed or Google Schloar.

 

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,b; Mooers 2019). We are also developing tools to ease the use of structural biology software like PyMOL by both begining and expert user. See our github site for more information and the 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 Python Workshop that meets every third Thursday of each month at noon in BRC 109 . This workshop provides a forum for local Python users to exchange knowledge about how they use Python programming in their research. The talks are recorded. The videos of the past talks can be found online. You may have to be on campus or connected to the campus network to view these videos. The speakers have been instructed to make the first half of their talks accessible to beginning users of Python. Anyone can volunteer to make a presentation. Some of the most accessbile presentations have been by graduate students. If you 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 the 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 faciities. 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 SSRL user for 20 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 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. That facility has complementary instruments . Dr. Mooers serves as the academic director of the BSC. Please contact Dr Mooers is if you want to add structural biology to your research.


Selected Publications:

(*corresponding author, ^co-corresponding authord, lab member, pdb codes from structures determined in my lab or by me):  

  • ^Mooers, B.H.M. (2019) Shortcuts for faster image creation in PyMOL. Protein Sci  PubMed PMID: 31710740   DOI: 10.1002/pro.3781
  • Terzyan SS, Shen T, Liu X, Huang Q, Teng P, Zhou M, Hilberg F, Cai J, ^Mooers, BHM, ^Wu J (2019). Structural basis of resistance of mutant RET protein tyrosine kinase to its inhibitors nintedanib and vandetanib. J Biol Chem 294(27):10428-37. Epub 2019/05/24. PubMed PMID: 31118272. doi: 10.1074/jbc.RA119.007682.  PDB IDs: 6NEC, 6NAJ, and 6NE7
  • Kumar V, Doharey PK, Gulati S, Meehan J, Martinez MG, Hughes K, ^Mooers BHM, ^Cruz-Reyes J.  (2019) Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes. PLOS ONE 14(4):e0211525. doi: 10.1371/journal.pone.0211525.
  • Cruz‐Reyes, J., Mooers, B. H., Doharey, P. K., Meehan, J., & Gulati, S. (2018)  Dynamic RNA holo‐editosomes with subcomplex variants: Insights into the control of trypanosome editing. Wiley Interdisciplinary Reviews: RNA, e1502. PMID: 30101566.
  • Liu, X., Shen, T., Mooers, BH, Hilberg, F., & Wu, J. (2018) Drug resistance profiles of mutations in the RET kinase domain. British Journal of Pharmacology 175:3504-3515. doi: 10.1111/bph.14395. PMID: 29908090.
  • ^Mooers, B. H. M. (2016)  Simplifying and enhancing the use of PyMOL with horizontal scripts. Protein Sci. 25(10):1873-82. PMID: 27488983
  • Cruz-Reyes, J.,  Mooers, B.H.M.,  Abu-Adas, Z., Kumar, V., & Gulati, S. (2016)  DEAH-RHA helicase• Znf cofactor systems in kinetoplastid RNA editing and evolutionarily distant RNA processes. RNA & Disease 3. pii: e1336.
  • ^Mooers, B. H. M. (2016) Direct-methods structure determination of a trypanosome RNA-editing substrate fragment with translational pseudosymmetry. Acta Cryst. D72, 477-487. doi: 10.1107/S2059798316001224. 5AD6.
  • Kumar, V., Madina, B.R., Gulati, S., Vashishti, A.A., Kanyumbu, C., Pieters, B., Shakir, A., Wohlschlegel, J.A., Read, L.K., Mooers, B.H.M. & Cruz-Reyes, J. (2016) REH2C helicase and GRBC subcomplexes may base pair through mRNA and small guide RNA in kinetoplastid editosomes.  J. Biol. Chem. 291,5753-64. doi: 10.1074/jbc.M115.708164
  • Criswell, A. and ^Mooers, B.H.M. (2015)  Structural studies of a double-stranded RNA trypanosome RNA editing by small-angle X-ray scattering. Methods in Mol. Biol. 1240, 191-216. doi: 10.1007/978-1-4939-1896-6_13. PMID: 25352145.

Link to full publication list >