Paul Hoeprich, Ph.D.

Chemistry, Materials and Life Sciences, Lawrence Livermore National Laboratory

Membrane-associated proteins and protein complexes account for 30% or more of the proteins produced by a cell.  These complexes mediate essential cellular processes such as signal transduction, transport, recognition, and cell-cell signaling.  As virtually all host-pathogen interactions are mediated through cell surface membrane associated proteins they are the key to understanding detection, pathogenicity and countermeasures.

Despite their importance, membrane proteins have remained challenging to study because of their marked insolubility and tendency to aggregate/precipitate when removed from their protein lipid bilayer environment. Techniques and methods for isolation, purification, and analysis developed with soluble proteins are not generally transferable or applicable to membrane-associated proteins and protein complexes.  We are addressing these problems by focusing on emerging methods for cell-free protein synthesis (IVT) and functional re-constitution of membrane proteins in phospholipid/protein (lipoprotein) nanostructures/nanoparticles.  We are exploring lipoprotein nanoparticle preparation methods for eventual use as a platform for stabilizing functional membrane proteins. Both lipoprotein nanoparticles and membrane proteins will be characterized using a suite of advanced, analytical methods.

Nanolipoprotein particles (NLPs) can serve as carriers of non-infective immunogenic proteins, e.g. H5 or N1 proteins (Avian influenza), as well as potential vaccine-based *_countermeasures_*.  NLPs containing selected microbial (bacterial or viral) cell-surface membrane proteins will provide an opportunity to better understand the science of *_pathogenicity._*  NLPs will enable capture and presentation of cell surface protein features associated with known biothreat organisms and potentially could aid in *_detection_* of emerging biothreats.