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 Optimization Projects (TOPs). The DBPs represent a range of biomedical science and include designed protein complexes (e.g., that can deliver cargos), aggregating proteins, membrane protein-lipid interactions, and RNA:protein complexes and their interactions with targets.

Protein:​Protein and Protein:Ligand 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,
  • David Baker (University of Washington), Design of de novo interleukin mimics for targeted immunotherapy
  • R. Kayed (UT Medical Branch, D. Eisenberg (UCLA), C. Keene (U. Washington), J. Kuret (OSU), Tau aggregates from Alzheimer's disease and related dementias
  • Jeffery W. Kelly (Scripps Research Institute), Probing the biochemical mechanism of amyloid disease and Probing the proteinopathy component of light chain amyloidosis
  • Erica Ollmann Saphire (La Jolla Institute for Immunology), Integrative immunogen design and testing

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.
  • Art Laganowsky (TAMU), Michael Marty (University of Arizona), Erin Baker (UNC), Ming Zhou (Baylor Medicine), Effect of lipid binding on membrane proteins
  • Kallol Gupta (Yale), Understanding organization of membrane proteins and lipids through lipid vesicles
  • Timothy Cover (Vanderbilt), Melanie Ohi (University of Michigan), Type IV Protein secretion in Helicobacter pylori

DNA/RNA:Protein Complexes

The final major set of DBPs have structural problems that are also quite challenging because they involve characterization of DNA/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 due to collaborations with the Center for RNA Biology at OSU. 

  • Matthew Disney (Scripps Florida), Targeted degradation of RNAs by using small molecules
  • Sarah Woodson (Johns Hopkins), Assembly mechanisms of RNA-Protein complexes for genetic control
  • Bruce Torbett (University of Washington), Stefan Sarafianos (Emory), Dynamics of HIV core interactions