Research Interests

Research efforts in the Flynn group emphasizes biophysical characterization of biologically active macromolecules using multidimensional/multinuclear solution NMR methods. Our approach emphasizes development of in vitro models of the cellular environment, and explores the influence of crowded environments on the behavior of proteins and small RNA oligonucleotide model systems.

Encapsulation of MacromoleculesReverse Micelle Model

Reverse Micelle ModelProteins, nucleic acid oligomers, and other biologically important macromolecules may be encapsulated within a surfactant shell (i.e., dioctyl sulfosuccinate) and transported into non-native solvent systems (i.e., short-chain n-alkanes). This novel approach opens up new opportunities for solution NMR studies of larger macromolecules, as well as providing a unique and powerful new approach to studies of the environment on the physical behavior of macromolecules. Current group effort are focused on the development of encapsulation as model of the crowded intracellular environment.

Schematic Diagram of Encapsulation of an RNA Oligonucleotide

Macromolecular Structure and DynamicsSolution Structure of 15.5K Protein

Solution Structure of 15.5K ProteinAll biological function derives from the structure and dynamics of macromolecules. Structure has long been used as the primary lead in efforts to understand the molecular basis of function, and remains fundamentally important. The importance of internal dynamics in proteins as a factor in characterizing function has become increasingly apparent, and solution NMR methods are particularly well-suited to evaluate such effects. Studies of backbone dynamics in proteins indicate that the main-chain atoms are generally highly and homogeneously ordered whereas studies of side-chain motion suggest a more heterogeneous picture. We are particularly interested in probing dynamics at the interfaces between components of protein-protein and protein-RNA complexes, across a wide range of time scales (from microseconds to hours) to characterize the full range of motion that influence the interaction. New efforts target characterization of dynamics in the RNA oligos, which promises to generate novel insights into the physical nature of protein-RNA recognition events.