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,
  • Erica Ollmann Saphire (Scripps Research Institute) and Sheng Li (UCSD), Function and assembly of the Ebola virus nucleocapsid (TR&Ds 2-5). 
  • Michal Sharon (Weizmann Institute), Regulatory principles of Cullin-ring ligases. (TR&Ds 2-5). 
  • David Baker (University of Washington), NIH PI, Design of denovo hetero-oligomers with orthogonal interaction specificity (TR&Ds 1-5). 
  • David Barondeau (Texas A&M University), Molecular mechanism of ISC iron-sulfur cluster biogenesis reveals by high resolution native mass spectrometry (TR&D 2).

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.
  • David Baker (University of Washington), Designed transmembrane proteins with cyclic symmetry (TR&Ds 1-3 and 5). 
  • Art Laganowsky (TAMU), Native IMMS of potassium inward rectifier channels: insight into gating and lipid binding (TR&Ds 1-3). 
  • Kevin Schey (Vanderbilt), Role of aquaporin-0 in lens development and aging (TR&Ds 1-3). 

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.

  • Mark Foster (OSU) and Paul Gollnick (U of Buffalo), Dynamics and allostery in protein-RNA regulation (TR&Ds 1-3).
  • Venkat Gopalan (OSU) and Susan Ackerman (UCSD), Spatiotemporal regulation of brain RNase P as a basis for neurological disorders (TR&Ds 1-5). 
  • 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).
  • Karin Musier-Forsyth (OSU) and Patrick Griffin (Scripps FL), RNA binding and packaging by retroviral gag proteins (TR&Ds 1-5). 
  • Sarah Woodson (Johns Hopkins), Hfq RNA chaperone and the mechanism of RNA- dependent regulation (TR&Ds 1, 3-5).