Research

Computational Research

Computational biophysics research at NC State is performed in the groups of Profs. Sagui, Roland, and Bernholc.
Currently the major effort of the computational biophysics group is to explore and characterize atypical DNA/RNA structures associated with Trinucleotude Repeat Expansion Diseases (TREDs). These diseases are caused by intergenerational expansion of simple sequence repeats which lead to severe neurodegenerative and neuromuscular disorders. The orgin of these are believed to be some slippage during DNA replication, repair, recombination or transcription. The focus of the research work of Profs. Sagui and Roland is therefore to understand they types of atypical DNA/RNA structures associated with these diseases and to explore the failure of DNA’s mismatch repair system in stabilizing toxic trinucleotide repeat expansions. The research makes use of large-scale atomistic modeling of the relevant biological molecules.
Additionally, the group of Prof. Sagui and Roland are also working on new algorithms for the accurate calculation of biomolecular free energies as implemented in the AMBER software package. Other research topics of current interest involve study of proteins with intrinsically disordered regions, investigations of transcription factors, and amyloid properties of prion-like proteins.

Experimental Research

The major thrust of experimental biophysics group are the dynamics of protein-DNA interactions at different length and time scales.  While Prof. Weninger uses atomic rulers to observe conformation changes on the scale of 2-8 nm, Prof. Wang uses atomic force microscopy to probe configurations of DNA-protein complexes at the scale of 2 nm to 1 micrometer.  Prof. Riehn uses nanofluidic manipulation to probe large DNA configuration under protein action at the scale of 300 nm to 100 micrometer.
Beyond that focus, Prof. Weninger’s laboratory is investigating intrinsically disordered proteins, protein folding in the nervous system, and membrane fusion in viruses.  His dominant technique is single molecule fluorescence resonance energy transfer (FRET).  Prof. Wang is investigating the 1-dimensional search process of proteins along DNA using a DNA-tightrope assay. She is developing novel techniques for achieving functional contrast (DNA versus protein) in atomic force microscopy.  Prof. Riehn is interested in nanofluidics, single-cell analysis, epigenetics, polymer physics, far-out-of equilibrium response of polyelectrolytes to electric fields.  His interests also include nanophotonics.
Prof. Lim is developing nanoparticle probes for biological imaging and analysis.  Current projects include plasmonic enhancement of upconversion particles (with Prof. Hallen), tracking of rotational motion of proteins traveling on DNA (with Dr. Wang), and electrically addressed microarrays for pathogen detection and identification.
Prof. Elting probes the mechanics of the mitotic spindle, the cytoskeletal machinery that aligns chromosomes during cell division and delivers them into two new daughter cells. She combines live cell confocal microscopy with mechanical perturbations such as laser ablation and molecular engineering, in both fission yeast and mammalian cells. She is also a member of the CFEP cluster on Modeling the Living Embryo.
Prof. Clarke studies the physics of nanomechanical, nanoelectric, and nanooptic systems.  She is investigating how electrospun nanofibers can be used as scaffolds for 3-dimensional cell and tissue cultures.
Prof. Daniels studies the nonlinear and nonequilibrium mechanics of soft materials, including biological-derived gels and lipids. She is particularly interested in understanding how elastic forces, capillary forces, and viscous forces interact to generate deformations, dynamics, and fracture.
Prof. Hallen develops optical micro-and nanoprobes.  He currently is using Raman microprobes to detect heme in dinosaur bones, and has worked on resonance Raman detection of DNA modifications and transfer of nuclear material from cells.

Research Funding

Most PhD students and all Postdocs are supported through external funding from the National Institutes of Health. We currently share 4 NIH grants and 2 NSF awards.  Most of these are multi-investigator awards and research is highly collaborative. Faculty have been recognized by a Sloan fellowship, a NSF CAREER award, a Burroughs-Wellcome award, and a K99-R00 career transition award.