Research Expertise and Interest
genomics, biophysical, bioanalytical, physical chemistry; laser spectroscopy, resonance Raman, excited-state reaction dynamics photoactive proteins, rhodopsins, microfabricated chemical biochemical analysis devices, forensics, infectious disease detection
Research Description
<p> The Mathies group uses modern laser spectroscopic techniques including resonance Raman spectroscopy, time-resolved vibrational spectroscopy, and femtosecond time-resolved absorption spectroscopy to study chemical and biological reaction dynamics with a particular focus on the mechanism of photoactive proteins that mediate information and energy transduction. Also, new high-sensitivity, laser-based detection techniques are used to facilitate the development of high-performance microfabricated chemical and biochemical analysis methods and "lab-on-a-chip" apparatus for genomic sequencing, genotyping, forensic identification and pathogen detection. </p> <p> Excited-State Structure and Reaction Dynamics. The quantitative analysis of resonance Raman vibrational scattering intensities is a powerful method for obtaining information on the excited-state structure and femtosecond reaction dynamics of photoactive molecules. This technique is being used to study polyenes, retinals and retinal-containing pigments, as well as the structure of the solvated electron. We are also developing the new time resolved vibrational structural technique called Femtosecond Stimulated Raman Spectroscopy that provides high resolution vibrational spectra of transient reaction intermediates with sub-100 fs time resolution. </p> <p> Photoactive Proteins. Visual excitation begins when a photon is absorbed by the 11-cis retinal chromophore in the visual pigment rhodopsin. The photoisomerization of retinal to the all-trans configuration drives conformational changes in the surrounding protein that excite the retinal rod cell. We are using a variety of low-temperature and ps-fs time-resolved spectroscopic techniques to determine how the excited-state isomerization occurs, how the protein catalyzes this process, how chromophore isomerization drives subsequent activating protein conformational changes on the ps-ns time scale, and how the protein controls the wavelength of maximum absorbance of visual pigments. We are also interested in understanding the photochemical mechanism of other light-sensing proteins such as phytochrome (a light sensor in plants), bacteriorhodopsin (a light-driven proton pump found in halophilic bacteria). </p> <p> Microfabricated DNA Analysis Systems. Laser-excited fluorescence is a sensitive detection method that lies at the heart of our work in bioanalytical chemistry. High sensitivity detection coupled with new fluorescent labels that exploit fluorescence resonance energy transfer has facilitated the development of high performance microfabricated chemical and biochemical analysis systems. Photolithographic methods are used to micromachine capillary electrophoresis systems and integrate them with DNA sample preparation microreactors. These novel devices provide ultra-high throughput sequencing for genomics, genotyping for health care diagnostics, and portable devices for point-of-care analyses, forensics, biothreat detection and space exploration. The overall goal is to develop chemical and biochemical microprocessors that will revolutionize chemical and biochemical analysis. </p>
