BROAD RESEARCH

Our goal is to develop and validate nanoparticle-based techniques for imaging single molecule interactions in live cells. We aim to introduce these tools in areas of basic science and medicine to introduce new cability for understanding basic cellular function and diagnosing disease.

Our work is seated in the multi-disciplinary field of bio-nanotechnology and nanomedicine. Our approaches include the areas of single molecule imaging, nanoparticle bioconjugate synthesis, and cellular neuroscience, in relation to the area of nanotechnology. We focus on the nervous system; however our tools can be broadly-applied to other biological systems.

Projects

Quantum Dot Probes for Single Molecule Imaging of Live Cell Dynamics.

QDs can be used as a utrasensitive probe to monitor extracellular and intracellular protein dynamics at a molecular level. We are tailoring the surfaces of quantum dots to serve as multifunctional neural probes to effect physiological and pharmacological responses through specific cell membrane receptor channels. Quantum dots are inorganic semiconductor nanoparticles that offer unique optical properties for cell identification. Their small size and surface-controllable properties offer great potential as building blocks for the attachment of select biomolecules for cellular delivery. Probes capable of provoking and localizing specific subcellular sites have wide-ranging applications for the development of tools and therapeutics targeted at understanding and regulating cell function.

Current projects involve creating QD bioconjugate probes to dyanamically track receptor movement in live cells. We have demonstrated that conjugation of quantum dots (QDs), fluorescent semiconductor nanoparticles, to ligand nerve growth factor (NGF) can be used to bind to TrkA receptors. Cells endoytose the NGF along with the quantum dot, allowing for a long term, intensely bright fluorescent imaging of receptor endoytosis and redistribution of QD-NGF-TrkAs. We observe that cells move NGF-QDs in a directed motion along cytoskeletal fiber tracks in long slender neurites. This is among the first examples of physiogically-relevant active shuttling of individual quantum dots in cells. Clinically-directed application: Determination of the effect of anti-depressants on cell signalling.

Novel Quantum Dot-based Hybrid Gel Method for Imaging Minute Biochemical Processes in Cells.

We have developed new hybrid gels for fractionating nanoparticle QDs and have shown that these gels cans be used to perform pull down of cell internalized QD probes. This method allows correlation of QD probe location in live cells with protein-protein associations. We are further extending this work to characterize the sensitivity and signal-to-noise limit of this technique and to apply this to disease diagnosis. Clinically-directed application: Identify minute changes in protein expression of stem/cancerous cells.

Novel Nano/Micro-Enabling Neurotechnologies.

One project involves a collaboratorative effort to design a nanowire-based electrode array for subcellular neural stimulation. A second collaborative project involves designing new microfluidic chambers for imaging neural subcellular activity.