Functional DNA conjugated magnetic nanoparticles for targeted MRI
Magnetic resonance imaging (MRI) is a powerful method for non-invasive three-dimensional imaging of cells and human bodies. One active area of research in this field is development of novel MRI contrast agents, particularly smart agents for small molecules or biomolecular markers in cells or human bodies. Superparamagnetic iron oxide nanoparticles (SPIOs) are a new class of contrast agents for MRI. Due to their biocompatible, biodegradable and magnetic properties they have, recently, been widely used for research and clinical purposes. Functionalization of SPIOs with several biomolecules is possible due to the polymer coating at the outer shell. These properties of SPIOs make them a great candidate for targeted contrast agents for in vivo applications. Herein we report the first example of smart MRI contrast agents based on the aptamer technology and magnetic nanoparticles which could be applicable to any molecule of choice. We have built a contrast agent for a protein, human alpha thrombin, which generates a dark signal with MRI as the thrombin is detected in the system. We have also built a smart turn-on MRI contrast agent for a small molecule, adenosine, which generates a bright signal as the analyte is recognized in the environment.
Live animal imaging of dendritic spine abnormalities in a mouse model of Fragile X Syndrome
Fragile X Syndrome is the leading inherited cause of mental retardation, and the only known genetic cause of autism. Although many abnormalities have been associated with the disorder, arguably the most consistent is a pattern of dendritic spine abnormalities found in patients and animal models. Specifically, the dendritic spines (thorn-like protrusions of the dendrite associated with a synapse) appear immature, often exhibiting abnormal length and shape, and found in higher than typical density in many brain regions. These abnormalities are consistent with the hypothesis that FMRP, the protein lacking in this disorder, regulates the normal developmental pruning of excess spines and synapses. However, directly testing this hypothesis is not possible using traditional methods because one has no record of the history and fate of particular spines. We therefore utilize in vivo, repeated, live animal 2-photon microscopy to track the fate of individual spines across developmental time. Using this method, we are examining spine formation and elimination rates, as well as changes in individual spine morphology, to determine what dynamic processes lead to the adult phenotype.
Understanding the aggregation of like-charged biopolymers via computer simulations
Many biological polymers carry a net negative charge. Despite the electrostatic repulsion acting between such charged biopolymers (polyelectrolytes), under physiological conditions they often aggregate to form compact, ordered bundles. This phenomenom, often referred to as "like-charge attraction" or "polyelectrolyte condensation", is a generic physical phenomenom that has been observed with DNA, F-actin (a major component of the cytoskeleton), and several filamentous viruses. For aggregation to occur, the presence of a positively charged "condensing agent" is typically needed. We use computer simulations to study the role of the condensing agent and the structure and stability of the polyelectrolyte bundles. One of the systems we study, involving the aggregation of F-actin in the presence of lysozyme (a globular protein), has particular relevance to the blockage of pulmonary passages in patients with cystic fibrosis. In this talk, I will discuss how our simulation results clarify and explain several recent experimental observations, and how they may be helpful in designing treatments for cystic fibrosis.