Current Research

Our research focuses on understanding structure, dynamics and function of complex macromolecular assemblies, biological tissues and inorganic materials in the solid state. We employ a wide range of techniques, encompassing multidimensional NMR spectroscopy, computational, biochemical, and X-ray diffraction methods to understand structural principles underlying protein-protein interactions and chemical reactivities of metal sites in metalloproteins and inorganic materials. Of particular interest to us are: i)physiologically important microtubule/cargo protein assemblies whose malfunction is associated with multiple diseases; ii)retroviral capsid protein assemblies associated with HIV-AIDS; iii)intervertebral disc tissues whose aging and damage cause the prevalent degenerative disc disease; iv) biotechnologically important vanadium haloperoxidases. Understanding structure, dynamics and function of these complex systems is critical for design of novel therapeutic and diagnostic strategies. We combine fundamental investigations in structural biology and biophysics with applied biomedical research seeking to develop novel magnetic-resonance-based diagnostic methods. Much of our research involves development of new solid-state NMR methods. Two representative directions are below. For description of other research projects, visit our group website: http://polenova.chem.udel.edu/.

Microtubule-Associated Protein Assemblies: Structure, Dynamics, Function:
Microtubules are an essential type of cytoskeleton and, together with their associated proteins, play important roles in a broad range of physiological functions. Microtubule-associated proteins are implicated in numerous diseases ranging from motor neuron and degenerative disorders, to neoplasia and viral infections. Atomic-resolution structures and dynamics of microtubule assemblies with their associated proteins are unknown due to their intrinsic insolubility and absence of long-range order. Lack of such insight hampers further research and impedes design of therapies against diseases associated with cytoskeleton dysfunction. Our long-term goal is to understand structural and dynamic basis of cargo transport regulation along microtubules by microtubule-associated proteins, in healthy and disease states. The focus of our NIH-funded research is determination of three-dimensional structures and dynamics of microtubule-associated proteins of dynein, dynactin and kinesin families. We employ multidimensional magic-angle-spinning NMR in conjunction with microscopy and other biophysical techniques.

Vanadium Enviironments in Vanadium-Containing Haloperoxidases and Bioinorganic Solids:
Biological roles of the trace element vanadium are intriguing yet poorly understood. Vanadium is a therapeutic agent for treatment of diabetes; recent discoveries of the anti-proliferative activities in vanadium compounds make them promising anti-cancer leads. However, its mechanism of action remains elusive, due to lack of appropriate spectroscopic probes. The overall goal of this NSF-funded project is development of 51V solid-state NMR spectroscopy as a novel probe of diamagnetic vanadium in proteins and bioinorganic systems. We have recently established 51V MAS NMR spectroscopy as the (only) direct, sensitive site-specific spectroscopic probe of vanadium cofactor in haloperoxidases. This approach will yield understanding of how the chemical reactivity of vanadium haloperoxidases is tuned by the environment at the vanadium, and will be generally suited for detailed investigations of the molecular mechanism of vanadium function in various biological processes.