Yi Pang, Ph.D. - US grants

The long-range scientific goals of the proposed project are to develop flexible conducting polymers for biomedical-related applications such as artificial muscles and controlled drug delivery. Our strategy is to develop new polymeric materials, which can exhibit large conformational change with fast response time under external stimuli. One of the objectives is to introduce a polar (cyano) or hydrophilic (carboxylic acid) functional groups as the side chains of the pi-conjugated poly(1,3-phenyleneethynylene) backbone. Recent studies from our laboratories indicate that such methodology could lead to flexible conducting polymers with improved dimensional response to external stimuli, thus opening the possibility for new applications. Another main objective of the proposed research will focus on investigating molecular folding-unfolding behavior of the developed polymers via spectroscopic methods such as UV-vis and fluorescence at variable temperature. Polymer conformation in good and poor solvents will be characterized by studying the polymer solution properties such as Mark-Houwink exponent and radius of gyration. This will be coupled with study of molecular aggregation, which can be induced by changing solvent/non-solvent ratio. Combination of spectroscopic data and molecular size information will allow us to establishing a broad scientific database to understand the folding-unfolding behavior of conducting polymers. The polymers developed in this proposal may exhibit excellent dimensional responses toward external chemical and electrical stimulus. Simple devices, therefore, will be built to test the dimensional response. The goal is to develop new polymeric materials, which can exhibit a wide range of conformational change and large macroscopic deformation under the external stimulus for biomedical applications.

DESCRIPTION (provided by applicant): Pyrophosphate anion (PPi) is involved in many biological processes that include ATP hydrolysis, DNA and RNA polymerizations, and enzymatic reactions. The anion is now emerging as a specific signaling molecule in bones and cells. The level of PPi in human tissue is directly related to various enzymatic activities, whose abnormal activities can cause diseases such as heart disease and Alzheimer disease. The detection of pyrophosphate is also an essential component in the commercial DNA pyrosequencing, which provides the necessary genetic profile for hospital patients. Although the genome-based medicine can dramatically increase the efficiencies in the patient treatment, the current high cost associated with the DNA sequencing prevents its routine applications. The development of low cost method for PPi detection, therefore, has a profound impact on the disease studies and DNA sequencing. The current method to detect PPi is based on a complicated enzymatic process, involving two enzymatic reactions occurring in sequence. A simple fluorescent detection of PPi could greatly reduce the cost for this step, which ultimately leads to price reduction for DNA sequencing. The proposed research is dedicated to find a simple solution for non-enzymatic detection of PPi. Our approach is to synthesize a chemical sensor that integrates a binuclear Zn(II)-Zn(II) core into 2-(2'- hydroxyphenyl)benzoxazole structure. The PPi binding to the sensor will trigger the excited state intramolecular proton transfer (ESIPT), thereby leading to a large optical response. Preliminary results show that the new pyrophosphate sensors can provide a fluorescence-based bioassay that greatly simplifies the current pyrophosphate detection scheme. The developed sensor has the potential to be used in DNA pyrosequencing. PUBLIC HEALTH RELEVANCE: Detection of pyrophosphate anion is an important element in DNA pyrosequencing, which currently uses the complicated enzymatic reactions and provides essential information for genome-based medicine. The proposed research focuses on the development of highly selective pyrophosphate sensor, which can greatly simplify the costly enzymatic detection scheme for DNA pyrosequencing and therefore reduce the DNA sequencing cost. Success in the proposed direction will have an important impact in achieving economically acceptable human genome analysis in a clinical setting.

NIR-Emitting Fluorescent Probes with Large Stokes? Shift for Improved Zebrafish Neuromast Imaging Project Abstract Loss of sensory hair cells in their function is one of the leading causes for deafness. In order to study the hair cell regeneration, zebrafish neuromast has been adopted as a model. The application aims to develop new fluorescent probes for neuromast labeling, in order to provide improved imaging tool for studying neuromast development. The investigation focuses on the synthesis of new cyanine probes that integrate the near infrared (NIR) emission property with ?excited state intramolecular proton transfer (ESIPT), thereby giving NIR emission with large Stokes? shift (??~260 nm). The molecular design will lead to the new probes that exhibit improved sensitivity and selectivity to label neuromast cells. Neuromast includes two different types of cells, i.e. hair cells and supporting cells. The current challenge in neuromast labeling is to display both hair cells and supporting cells, while being able to distinguish one type of cells form the other. The proposed research is search for new neuromast labeling reagents that can simultaneously label both hair cells and supporting cells. In addition, the proposed research also examine the impact of zinc on the neuromast development.