Current Areas of Research

High Dipole Moment Organic Materials
Membrane Binding Proteins
Nucleic Acid Structures and Dynamics
EPR Information (PowerPoint, 5.8M)

High Dipole Moment Organic Materials

How can organic chromophores be processed on a large scale to produce highly efficient semi-conducting materials?

Organic chromophores, which have high dipole moments, are becoming increasingly important in electro-optic applications. These materials may soon replace many of the metal oxides currently used in the semiconductor industry. Their efficiency is limited however, by the inability of materials designers to fully orient large arrays of such chromophores, as outlined in this paper in Science, April, 2000.

As part of the NSF-funded Science and Technology Center to develop materials for information technology, we are investigating the origin of the difficulty of alignment of these materials using Monte Carlo methods of statistical mechanics. We have theoretically explained the experimental observation that the large dipole moments make chromophore alignment at high concentrations impossible using current strategies. The theoretical work parallels the experimental work, as we investigate the possible improvements in performance by embedding chromophores into dendritic materials, or attaching them to polymeric backbones. We are currently investigating methods to overcome the dipolar interactions that make alignment a problem. We are building EPR-active analogs of the high dipole moments chromophores to directly measure the order of these large arrays.

4 Moments of Distribution
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3-arm Dendrimer Chromophore
Chromophores
DARPA 11/2002
DURINT 11/2002
 
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Membrane Binding Proteins

What are the general principles used by signaling-proteins to recognize membrane surfaces?

We have used the "Spin Relaxant EPR" method to determine the orientations of several membrane-binding proteins to the varied membrane surfaces. We have studied bee venom Phospholipase A2 (bvPLA2), and clearly determined that the primary attachment site is near the active site of the enzyme. This provides a physical basis for the model of bvPLA2 action - called the "scooting model" - which states that the enzyme remains attached but moves among sites to cut the phospholipids.

We are looking at a variety of different proteins and mutants of those proteins to determine the motifs used by signaling-proteins to recognize membrane surfaces. The systems being examined include the distress signaling proteins Cytosolic Phospholipase A2 (cPLA2) (signaling production of eicosinoids and prostaglandins), Phospholipase-C (the delta-1 isoform) (signaling calcium uptake and release), and Factor VIIIa (signaling release of thrombin). Please see our JBC paper.

Bee Venom PL A2

Docking Orientation of Bee Venom Phospholipase A2 as Determined by the Interaction of EPR Spin Labels (Red/Blue Groups) with a Gradient of Ionic Spin Relaxants (not shown) Above the Membrane Surface.

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Presentation at Royal Society of Chemistry, Warwick, UK
Presentation at NCS
Biophysical Society Poster, 2004
 
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Nucleic Acid Structures and Dynamics

What features of the structures of DNA are important in protein recognition?

In particular, the internal motions of DNA play a significant role in the energetics of DNA binding and protein recognition. We study the modes of motion of DNA to determine the types of dynamics accessible to DNA. We have developed a dynamic-sensitive probe that is sensitive to Electron Paramagnetic Resonance (EPR) Spectroscopy. The probe is covalently linked to a base pair and may be incorporated into an oligomer of DNA at will. These probes have been used to test the theories on elasticity, and determine the dependence of DNA flexibility on base composition and sequence. To read more about how we determine the fundamental dynamic properties, please read our PNAS paper from April, 2002.

We are using EPR and the spin labels to probe the structures of RNA, such as the TAR binding site, at a variety of spin labeled sites and comparing the relative changes in dynamics of the spin probes when binding, by proteins such as the TAT protein. See the articles in JACS, 2001, and 2002.

Duplex DNA with modifications

Single turn of duplex DNA wherein the base pairs have differntial flexibility dependening on where a modification has been made in which a phosphate group (carrying a -1 charge) has been replaced by a methylphosponate group which is uncharged.

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Presentation at NCS
 
 
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