Intercalation-mediated Nucleic Acid Assembly, The Molecular Midwife & the Origin of Life, Nucleic Acid-Cation Interactions, Understanding DNA & RNA Condensation.
The research in our laboratory is directed towards elucidating the fundamental chemical and physical principles that govern nucleic acid (RNA and DNA) assembly. We are interested in how the physical properties of nucleic acids govern biological functions in contemporary life, and how these same properties provide clues to the origin and early evolution of life. We are also applying our knowledge of nucleic acids to problems that are of current importance in medicine and biotechnology. Specific projects include investigations of: 1) the origin and evolution of RNA; 2) cation, solvent and small molecule interactions with nucleic acids; 3) nucleic acid condensation and packaging; and 4) folding and evolution of the ribosome. Our research involves the application of a wide variety of physical and chemical techniques.
A. Nanoscience: Synthesis and Study of the Properties of Nanomaterials of Different Shape: The type of electronic motion in matter determines its properties and its applications. This motion is determined by the forces acting on the electrons, which in turn, determine the space in which they are allowed to move. One expects that if we reduce the size of material to below its naturally allowed characteristic length scale, new properties should be observed which change with the size or shape of the material. These new properties are different from those of the macroscopic material, as well as of its building blocks (atoms or molecules). This phenomenon occurs on the nanometer length scale. Our group makes and studies the properties of these nanometer materials. The properties examined are:
Ultrafast electron-hole dynamics in semiconductor nanoparticles and composites
Shape-controlled synthesis and stability of metallic nanoparticles
Enhanced light absorption and scattering processes, electronic relaxation, and photothermal properties of gold and silver nanocrystals of different shapes
B. Nanotechnology: Potential Use of Nanoparticles in: a) Nanomedicine - Diagnostics and Selective Photothermal Therapy of Cancer: When gold or silver nanoparticles are conjugated to cancer antibodies or other cancer targeting molecules, the cancer cells selectively labeled with those nanoparticles and can be easily detected under a simple microscope due to their strongly enhanced light scattering properties. The fact that these nanoparticles can also absorb light strongly and rapidly convert this energy into heat allows for the selective destruction of cancer cells at laser energies not sufficient to harm surrounding healthy cells. The concept of plasmonic photothermal therapy has been demonstrated in both cell culture and in live animal models in our laboratory. In addition, we are also researching the use of plasmonic particles as selective drug delivery and imaging contrast agents. b) Nanocatalysis - Shape Dependent Catalysis: Due to their large surface to volume ratio, nanoparticles are expected to be good catalysts. Since different shapes of nanoparticles made of the same material have their surface atoms arranged differently, one expects them to have different catalytic properties. In our group, we are examining the effects of both the nanoparticle shape and the cavity size of hollow nanoparticles on the catalytic properties of transition metal nanocrystals. We are also studying the shape-stability of these nanoparticles in the harsh chemical environment of the catalytic reactions in colloidal solution. c) Plasmonics: The intense electromagnetic fields generated at the surfaces of noble metal nanoparticles – localized surface plasmons – are known to enhance radiative and non-radiative processes, as well as energy transfer processes in nearby molecules and compounds. By combining plasmonic particles with biomolecular photosystems, the rates of important chemical processes, such as retinal isomerization in photosynthetic baceriorhodopsin (bR) and its associated proton pump rate, can be tuned. This property was recently used to enhance the photocurrent from bR by a factor of 5000. Rates of radiative (emission) and non-radiative relaxation in excitonic systems, such as semiconductor quantum dots and rods, can also be dramatically enhanced by plasmon coupling interactions. LDL also studies the fundamental interactions of plasmons as they couple to one another in individual (i.e. nanoshell and nanocage) particles, as well as in groups of nanoparticles as their size, shape, distance, and orientation are varied.
We develop chemical and biological tools for research in a wide range of fields. Some of them are briefly described below; please see our group web page for more details.
Chemistry, biology, immunology, and evolution with viruses. The sizes and properties of virus particles put them at the interface between the worlds of chemistry and biology. We use techniques from both fields to tailor these particles for applications to cell targeting, diagnostics, vaccine development, catalysis, and materials self-assembly. This work involves combinations of small-molecule and polymer synthesis, bioconjugation, molecular biology, protein design, protein evolution, bioanalytical chemistry, enzymology, physiology, and immunology. It is an exciting training ground for modern molecular scientists and engineers.
Development of reactions for organic synthesis, chemical biology, and materials science. Molecular function is what matters most to our scientific lives, and good chemical reactions provide the means to achieve such function. We continue our efforts to develop and optimize reactions that meet the click chemistry standard for power and generality. Our current focus is on highly reliable reversible reactions, which open up new possibilities for polymer synthesis and modification, as well as for the controlled delivery of therapeutic and diagnostic agents to biological targets.
Traditional and combinatorial synthesis of biologically active compounds. We have a longstanding interest in the development of biologically active small molecules. We work closely with industrial and academic collaborators on such targets as antiviral agents, compounds to combat tobacco addiction, and treatments for inflammatory disease.
Our research focuses on LC-MS based proteomics and its biomedical applications. Novel MS based methods are being developed to characterize proteins, especially protein post-translational modifications (PTMs). MS-based large-scale analysis can systematically identify and quantify proteins and their PTMs for the different states of cells or tissues, such as cancerous samples. This may provide a better understanding of the function of proteins, the role that proteins play in physiological and pathological processes, cell signaling, cell metabolism, and the relationship between proteins and cancer.
Mass Spectrometry (MS) is one of the key analytical methods used to identify and characterize small quantities of biological molecules embedded in complex matrices. Although MS has found widespread use, improvements are still needed to extend its application to the grand challenges of this century.
Since starting my position at Georgia Tech in 2004, my group members and I have used an integrated strategy with roots in bioanalytical chemistry, instrumentation development, bioinformatics, and theoretical modeling to focus on questions of great societal and scientific significance. To this purpose, we have integrated with cross-cutting teams devoted to problems that range from explaining the origins of life on Earth and diagnosing cancer at an early stage, to tracking the sources and prevalence of counterfeit pharmaceuticals worldwide. The common theme along these questions is the need for highly accurate tools for quantifying, identifying, and imaging trace chemicals in complex mixtures.
Research in our lab uses state-of-the-art mass spectrometry, ion mobility gas-phase separations,ultrahigh performance liquid chromatography, and new soft ion generation techniques. We investigate the obtained data using machine learning and other powerful bioinformatic approaches. Our group is very dynamic, and each student pursues more than one project at a time, usually in collaboration with other group members or with other research groups at GT or elsewhere. Graduate and undergraduate students are trained in a variety of bioanalytical instrumentation/methodologies, with an emphasis on the fundamentals. We are analytical mass spectrometrists at heart, and strive to answer "big" scientific questions or questions with a large societal impact.
Metals In Biological Systems. Approximately one third of all known proteins contain metal ions as cofactors and serve a wide variety of functions, such as structure stabilization, catalysis, electron transfer reactions or complex tasks, including signal transduction and gene regulation. Numerous diseases such as haemochromatosis or Menkes disease were found to be related with a defect in metal metabolism. Research is concerned with development of metal specific fluorescent probes for the investigation of the intracellular chemistry of trace elements, the mechanistic study of metalloprotein catalyzed reactions with unusual coordination geometries as well as the development of protein-based, semisynthetic organometallic catalysts in aqueous solution.
Fluorescence Probes and Chelators for the Investigation of Intracellular Storage, Trafficking, and Homeostasis of Trace Elements. Until recently, little was known about how eukaryotic cells take up metal ions or regulate intracellular concentrations. Fluorescent chemosensors have been proven to be powerful and nondestructive tools for the study of intracellular metal ion distributions and have provided a wealth of information, including control of muscle contraction, nerve cell communication, hormone secretion, and immune cell activation. Research is concerned with the development of highly specific fluorescent probes for the detailed mechanistic investigation of copper storage and trafficking. Distribution and changes of intracellular copper concentration can be followed in vivo using fluorescence microscopy. Various combinatorial fluorophore libraries are being synthesized, which subsequently are screened for copper binding selectivity.
Bioorganometallic Catalysis with Peptide and Protein Ligands. The distribution of metal ions in sea water can be directly correlated with their abundance in biological systems. Consequently, the platinum metals palladium, rhodium, iridium and platinum are not found in any of the natural occurring metalloproteins. Nevertheless, these cations are excellent catalysts for a wide variety of organometallic reactions. Research is focused on combining the rich chemistry of platinum metals with the advantage of proteins to catalyze reactions with high regio- and stereo-selectivity. Novel bioorganometallic catalysts are being developed via redesign of structurally well characterized proteins.
Biochemistry, biomolecular structure and function, chemical biology, energy and sustainability, molecular biophysics, physical chemistry, spectroscopy and dynamics
Research in my group is focused on how the dynamic and responsive protein matrix facilitates biological catalysis. We use a wide range of high resolution spectroscopic, biochemical, and structural techniques to describe the reaction coordinate, which reveals the motion of the protein in space and time. We test the design principles, which we uncover, by building biomimetic models.
Method Development. Our group is interested in the design of efficient methodologies to accomplish the formation of carbon-carbon and carbon-heteroatom bonds with the intent to apply the methodology toward the synthesis of complex natural and unnatural targets.
Natural Product Synthesis. Approaches to natural products not only inspire the development of new synthetic strategies, but often unveil unexpected and often interesting reactivity. Targets are chosen for their interesting biological activity along with their sheer complexity. We are interested in exploring both modular and convergent approaches to complex targets that enable facile derivatization for the development of combinatorial libraries.
Medicinal Chemistry. Medicinal or pharmaceutical chemistry lies at the intersection of chemistry and pharmacy. Our group is interested in the design, synthesis and development of pharmaceutical drugs, or other chemical entities suitable for therapeutic use. We are further interested in the study of their biological properties and their quantitative structure-activity relationships (QSAR). Given that medicinal chemistry is a highly interdisciplinary science, we aim to establish several collaborations with biologists, biochemists, and computational chemists to facilitate the design and development process. In particular, we aim to develop therapeutics toward the treatment of various forms of cancer, HIV, diabetes, and neurological disorders, such as Alzheimer's and Parkinson's disease.
Professor May is interested in rational, molecularly based approaches to problems in neurochemistry, in the development of novel enzyme effectors such as suicide substrates and transition state analogs, and in basic mechanistic studies on enzymes involved in the biosynthesis, metabolism, interconversion and regulation of neurotransmitters, neuroregulators and biologically active neuropeptides and peptide hormones. Both chemical and physical techniques are being used to investigate the structure and reactivity of these enzymes, and detailed stereochemical and structural studies on substrates, products, and inhibitors are being pursued. In addition, pharmacological techniques are being utilized in order to evaluate the action of novel enzyme effectors on cardiovascular and neurological functions. Dr. May's group has established a special cell culture laboratory which is used extensively in their neurochemical work.
Metalloproteins constitute one of the largest classes of proteins in the proteome and are involved in virtually every metabolic and signaling pathway of consequence to human health and disease. Broadly speaking, the Reddi laboratory is interested in determining the cellular, molecular, and chemical mechanisms by which metalloproteins are activated by cells, and once activated, how they communicate with other biomolecules to promote normal metabolism and physiology, placing an emphasis on systems relevant to cancer, neurodegenerative disorders, and infectious diseases. Current projects in the lab are focused on elucidating heme trafficking pathways and the role of Cu/Zn Superoxide Dismutase (SOD1) in redox signaling. Prospective students will get broad training in disciplines that span modern biochemistry, bioinorganic chemistry, biophysics, chemical biology, molecular genetics, and cell biology.