Driving Biomedical Projects

Carefully-selected Driving Biomedical Projects (DBPs) that have both biomedical significance and substantial technical structural characterization challenges are the drivers and testbeds of the Technology and Research Development projects (TR&Ds). These are grouped into three main categories: soluble protein:protein complexes, membrane protein complexes (with and without lipids/ ligands), and RNA:protein complexes.

Protein:​Protein Complexes

The first set of investigators have structural questions involving interactions of soluble proteins with other proteins or ligands. Their structural problems are difficult ones. In certain cases, native MS is the only way to make the desired measurements,
  • DBP 1: Erica Ollmann Saphire (Scripps Research Institute) and Sheng Li (UCSD), Function and assembly of the Ebola virus nucleocapsid (TR&Ds 2-5). NIH R01 AI118016.
  • DBP 2: Dieter Wolf (Sanford Burnham Prebys Medical Discovery Institute) and Michal Sharon (Weizmann Institute), Regulatory principles of Cullin-ring ligases. (TR&Ds 2-5). NIH R01GM121834.
  • DBP 3A: David Baker (University of Washington), NIH PI, Design of denovo hetero-oligomers with orthogonal interaction specificity (TR&Ds 1-5). Project funded by NSF and Calico.

Membrane Protein Complexes With and Without Lipids

Membrane proteins are highly relevant biomedically. They serve as targets for >50% of drugs on the market, for example, but their characterization is particularly challenging. In spite of this, Wysocki and Laganowsky have recently published high quality s
  • DBP 3B: David Baker (University of Washington), Designed transmembrane proteins with cyclic symmetry (TR&Ds 1-3 and 5). NIH PI.
  • DBP 4: Art Laganowsky (TAMU), Native IMMS of potassium inward rectifier channels: insight into gating and lipid binding (TR&Ds 1-3). NIH DP20D022672.
  • DBP 5: Kevin Schey (Vanderbilt), Role of aquaporin-0 in lens development and aging (TR&Ds 1-3). NIH R01EY013462.

RNA:Protein Complexes

The final major set of DBPs have structural problems that are also quite challenging because they involve characterization of RNA:protein complexes. The RNA samples often need to be folded in relatively high concentrations of Mg2+ which can complicate the spectra by adducting to the samples. In addition, the RNA preparation procedures often lead to heterogenous populations of RNA with different lengths, splitting the signal over multiple peaks. The Wysocki group has obtained extensive experience in the native MS characterization of RNA:protein complexes because of the strong Center for RNA Biology at OSU. By continuing to build our expertise on these types of samples, nucleoprotein investigations nationally and internationally will be provided with useful protocols for characterization of stoichiometry, connectivity, and CCS of RNA protein complexes.

  • DBP 6: Mark Foster (OSU) and Paul Gollnick (U of Buffalo), Dynamics and allostery in protein-RNA regulation (TR&Ds 1-3). NIH R01GM120923.
  • DBP 7A: Venkat Gopalan (OSU) and Susan Ackerman (UCSD), Spatiotemporal regulation of brain RNase P as a basis for neurological disorders (TR&Ds 1-5). NIH R21NS096600.
  • DBP 7B: Venkat Gopalan, PI (OSU) with OSU collaborators Michael Poirier, Mark Foster, Vicki Wysocki and Northwestern University collaborator Julius Lucks. Dissecting functional cooperation among subunits in a catalytic ribonucleoprotein (TR&Ds 1-5). NIH R01GM120582.
  • DBP 8: Karin Musier-Forsyth (OSU) and Patrick Griffin (Scripps FL), RNA binding and packaging by retroviral gag proteins (TR&Ds 1-5). NIH R01GM065056.
  • DBP 9: Kotaro Nakanishi (OSU), Target specificity of human RNA-induced silencing complex (TR&Ds 1-4). NIH R01GM124320.
  • DBP 10: Sarah Woodson (Johns Hopkins), Hfq RNA chaperone and the mechanism of RNA- dependent regulation (TR&Ds 1, 3-5). NIH R01GM120425.

Click here to view how TR&Ds and DBPs function together.