The Department of Chemistry and Biochemistry
Title, Principal Investigator and Abstract for the 2015 A Look Ahead UMBC Faculty Poster Session
Naturally Synthetic: Using Biology to Improve Technology
Nature has a diverse toolkit that can be utilized to address a broad array of important chemistry related problems. Among these tools are DNA, lipids, polysaccharides, and proteins, each of which has been used for direct applications from sensors to electronics. Among these macromolecules, proteins represent nature’s most diverse polymer with a range of functionality determined by 20 naturally encoded amino acids. The structure and amino acid makeup of a protein or polypeptide determines its properties, in this presentation I will discuss how these chemical functionalities can be exploited to improve materials.
The focus of my group is to identify functional polypeptides for the purpose of improving technologically relevant materials. Our lab uses a technique called phage display in order to identify solid binding polypeptides that are specific for binding to and the mineralization of electroactive materials and use these materials to prepare new lithium ion batteries. Once peptides are identified, they will be synthesized and combined with other peptide chains that have already been isolated that bind to carbon nanotubes (CNTs) to make multifunctional polypeptides. My research is multidisciplinary and involves the integration of biology, biochemistry, synthesis and nanomaterials science in order to address significant problems.
Cellular Biochemistry: Reversible Compartments of Metabolic Pathways in Living Cells
Sequential metabolic enzymes have long been hypothesized to form transient multienzyme complexes to regulate metabolic pathways in cells. Dr. An as a lead and co-corresponding author discovered human de novo purine biosynthetic complex, the purinosome, by employing fluorescence single-cell microscopy in the field of enzymology (An et al. Science (2008) 320, 103-106). Dr. An and co-workers are interested in elucidating purinosome-associated signaling pathways in order to address the biological significance of the purinosome in human cells. In addition, Dr. An and co-workers have obtained compelling evidence supporting the existence of another reversible metabolic compartment for human glucose metabolism. It is anticipated that its reversibility may explain how the direction of glucose-mediated carbon flux is regulated inside a cell and why glucose metabolism is susceptible to be manipulated in human diseases. Accordingly, we have started integrating spatiotemporal relationships between purine biosynthesis and glucose metabolism with strong emphasis on signaling pathways. Ultimately, we will visually elucidate an intracellular interaction network between metabolic and signaling pathways. Given that de novo purine biosynthesis and glucose metabolism have been validated targets for anticancer chemotherapy, we are enthusiastic to study the intracellular interaction network between metabolic and signaling pathways in human cancer cells with a goal of translating our spatiotemporal understanding of metabolic pathways into better cancer therapies.
Biomedical, Biodefense and Physiological Optical Sensing Group
The development of novel optical sensing and imaging technologies for the detection and monitoring of specific chemical species at the macroscopic and nanoscopic levels are described in this poster. In particular, the development of novel implantable, intracellular nanosensors and nano-imaging probes capable of rapidly detecting biomarkers of significance to bio-medical and/or bio-defense applications are highlighted. These sensors and imaging methodologies offer a great potential for better understanding the mechanisms of numerous biochemical reactions and their pathways by allowing for the simultaneous monitoring of many species of interest in real-time. Applications include pre-symptomatic disease monitoring to surgical guidance methodologies for more accurate medical procedures.
Gold Nanoparticle-Based Platforms for Theranostic and Multimodal Imaging Applications
Gold nanoparticle (GNP) platforms possess unique properties that make them valuable tools for diagnosis, drug delivery and the monitoring of disease progression.
Using GNPs, one main project in Daniel’s group is to simultaneously target synergistic therapeutic agents to tumors, and monitor the therapeutic response in real-time by magnetic resonance imaging. This approach has the advantage of decreasing chemotherapeutic dose, toxicity and drug resistance while increasing treatment efficiency. GNPs are decorated with polypropylene imine dendrons modified at the termini with targeting, imaging and therapeutic moieties, selected based upon the type of cancer that is to be targeted.
Another lead project in Daniel’s group aims at monitoring cardiovascular diseases. For this purpose, GNPs have been used as contrast agent for X-ray CT imaging of angiotensin-converting enzyme (ACE). The overexpression of ACE has been associated with increased risk of heart failure. We have been using Lisinopril (an ACE inhibitor) as the targeting agent, and its conjugation to GNPs creates a valuable probe for monitoring ACE expression as a function of disease progression. GNPs also coated with MRI label enable bimodal imaging of ACE utilizing MRI and X-ray CT.
A recent project, in collaboration with Dr. Badano (FDA), Dr. Garcin (UMBC, Biochem) and Dr. Kann (UMBC, Bio) focuses on creating a new technology for in vivo detection of protein-protein interaction. Indeed, only 15% of protein-protein interactions are known, and these interactions are key steps to many biological phenomena. The overall goal is to develop protein-protein interaction reporters for a non-invasive imaging technique such as small-angle X-ray scattering (SAXS). The reporter agents selected are GNPs: we have first prepared GNPs dimers with no protein, in order to study the expected signal for the detection of protein-protein interaction. Once fully developed, this new technology could become an important tool for understanding diseases at the molecular level.
Structural Biology in the Garcin Lab
We study how proteins work via conformational changes, posttranslational modifications, and protein:protein interactions. Our research areas include proteins in the nitric oxide-sGC-cGMP pathway crucial to the cardiovascular system, nitrogen oxides modifications, non canonical protein:RNA interactions, ligand:protein interactions and novel methods to detect protein:protein interactions.
Our expertise, including molecular biology, biochemistry, spectroscopy, x-ray crystallography, and small-angle x-ray scattering, allows us to answer key questions regarding enzyme catalysis, inhibition, recognition, and structural plasticity.
Probing the Internal and External Structure of Carbon Nanodots through Fluorescence Quenching
Chris D. Geddes
In past several years, there has been significant investigation into the various synthetic routes of carbon nanodots along with their associated photophysical properties1-3. Carbon nanodots are naturally fluorescing nanometer-sized particles with interesting and unique photophysical properties, which make them highly applicable for various applications in the life sciences2-3. Our lab has been investigating these particles produced by various combustion routes for many years, studying both the photophysical and plasmon-enhanced photophysical properties1. In order to fully understand the photophysical properties of carbon nanodots, in this poster we have examined the both the internal and external structure of these particles in an attempt to ascertain the origins of the fluorescence signature/s, using a combination of differently charged ions; which ultimately results in both static and dynamic quenching processes being observed. Our results reveal significant vibronic structure of the nanodots’ chromophore, which can readily be quenched by non-charged ions (acrylamide), suggesting a buried fluorescent chromophore center.
Spectral Distortions in Metal-Enhanced Fluorescence
Chris D. Geddes
In recent years our laboratory and others have demonstrated many examples and concepts in Metal-Enhanced Fluorescence1 (MEF), a surface plasmon phenomenon, which amplifies both fluorescence and luminescence signatures in the near-field, i.e. less than one wavelength of light away from a metallic object. In all of these examples of MEF, and for over a decade, the fluorescence spectra has simply been reported as being enhanced, i.e. the emission is greater from a plasmonic substrate as compared to a suitable control sample.
However, in this paper we will show that Metal-Enhanced Fluorescence from both a variety of plasmonic substrates and using a range of different fluorophores, often results in fluorophore spectral distortion. More often than not, the red edge of the fluorescence spectra is observed to be distorted, as compared to the emission spectra of a fluorophore observed in the far-field and distal from plasmonic interactions. In addition, a significant MEF effect often results in notable changes in the spectrum full width at half maximum (FWHM). We discuss these new effects in terms of the mechanism of plasmonic enhancement.
DNA Binding Proteins and Drug Delivery Vehicles: Tales of Elephants and Snakes
I have a long-term interest in protein-nucleic acid interactions, the interplay of thermodynamics and kinetics in regulating the function of these proteins, and the involvement of these proteins in disease processes. My studies have focused on the details of molecular recognition, understanding how the binding affinities and specificities of these proteins are related to their structures. Much of my research in this area has dealt with single-strand specific nucleic acid binding proteins (also known as helix-destabilizing proteins). As a class, these binding proteins have a wide range of biological roles, yet they share a number of biochemical commonalities.
The single-stranded DNA binding proteins under current investigation include bacteriophage T4 gene 32 protein, involved in DNA replication, recombination and repair, and the nucleocapsid (NC) proteins of retroviruses (including HIV), which have a role in viral RNA packaging and replication, and act as “chaperones”, facilitators of nucleic acid conformational change. We have used our expertise in this area to study a nucleic acid binding protein, crotamine, a major component of the venom of the South American rattlesnake. Crotamine is a cell-penetrating peptide, and is unique in that it selectively delivers plasmid DNA into actively proliferating (AP) mammalian cells. Crotamine could serve to selectively target malignant cells with both nucleic acids and intracellularly-expressed gene products.
Seeing is believing: from single molecules to biological networks in cells
Our research focuses on developing and applying novel bioanalytical and biophysical tools to understand molecular underpinnings of how signaling pathways cross-link with metabolic pathways in cancer cells. Two current projects are 1. Develop an advanced versatile nano-reaction chamber to enable detecting transient interactions between single set of enzyme molecules in confined dimensions, and 2. Develop a novel super-resolution imaging technique to map critical biological pathways in live cells. Ultimately, we aim to determine how signaling regulators (proteins) are spatially and temporally involved in cancer cell development and survival by employing proposed innovative in vitro and live cell techniques. In our lab students are trained in cross-disciplinary research at the chemistry-biology-physics interface by building cutting edge microscopy systems, fabricating nano-reaction chambers and flow cells and imaging the interactions between biomolecules in real time in vivo and in vitro.
Advanced Applications in Bio-analysis
William R. LaCourse
The LaCourse Group at UMBC is dedicated to developing new analytical methods which focus on solving problems and developing new technologies. Current projects include: analysis of enzymatic reactions and bioprocesses, aqueous copper sensors and method development, carbohydrate profiling of therapeutic glycoproteins, mass spectrometric detection of taste and odor causing compounds in aquaculture, development of a multi-functional TLC plate/surface analysis ambient ionization platform for mass spectrometry, and development of a colorimetric sensor to detect biogenic amines in spoiled food.
The Interplay of Molecular Structure and Energetics
There are ca. 100 hundred known chemical elements and a hundred million known chemical compounds. The number of chemical species is greatly enhanced on including reactive intermediates as found in the mass spectrometer, solution and solid matrices: gas phase protonated ions being of major concern. There are even more elements if we include the recently discovered higher trans-actinide elements and light isotopes of hydrogen such as muonium and positronium.
My studies have traversed the periodic table. Elements of my greatest activity have been fluorine, the noble gases, boron and “of course” carbon. There are many chemical properties that may be measured and/or calculated – my own studies have gone from A to Z, from aromaticity (the topic of my recent NSF grant submittal) to zero-point energies (a quantity easily studied and even more easily ignored). Heats of formation have been of major concern, studies of heats of vaporization, has also seen considerable activity.
I wish to find regularities in chemical behavior and understand chemical understanding, and yet I revel in anomalies and that which is inconsistent and incomplete in our knowledge. My research is international in scope – my major coworkers have been in Germany, Israel, Portugal, Slovenia, Spain and Missouri and the newest countries of my collaborators are in Argentina and Morocco.
Proportionally to date, I have fewer publications with USM colleagues, individuals numbering but eight from UMBC, two from UMCP and one apiece from Frostburg and UMUC. How can we increase that amount of local combined activity?
In order to find areas for possible interface and exploration, I now ask my favorite question of colleagues and of future coworkers – “What is your favorite compound, and why?”
I “look forward” to the resulting dialogue with you, on, hopefully, a new collaborative project of mutual interest and activity.
Novel Fluorophores for in vivo Bioimaging
Fluorescence bioimaging is a powerful tool for medicinal diagnosis. In our lab we work on developing a novel generation of fluoropheres, which will significantly expand the capability of medicinal fluorescence diagnosis. We have developed a series of energy transfer arrays, which utilizes hydroporphyrins – synthetic analogs of photosynthetic pigments, as a fluorescent entity. Energy transfer arrays, which are composed of hydroporphyrins, and additional pigments, allow creating fluorophores with unprecedented properties: multiple excitation wavelengths and tunable near-IR emissions. Novel fluorophores will be utilized in multicolor, fluorescence-guided surgery.
Next Generation Benign by Design Functional Nanomaterials
The research program in the Rosenzweig laboratory aims to understand at the molecular level the interactions between synthetic nanomaterials, and environmental and biological systems. Understanding these inherently complex interactions is imperative to the development of “benign by design” nanomaterials that minimally impact human health and the environment while retaining desirable functions and performances. The Rosenzweig laboratory is a member of a nationally distributed NSF Center for Sustainable Nanotechnology, which brings together a diverse group of researchers with expertise in materials science, chemistry, biology, and toxicology. Research projects in the Rosenzweig laboratory involve the development of new techniques for the synthesis and characterization of optical nanomaterials. We aim to synthesize composite nanomaterials, and demonstrate their utility in a wide range of applications including biomedical imaging, biosensors, targeted therapy, and photo-catalysis and energy harvesting. Four research projects are described in this poster: a) studying the growth and degradation of CdSe/ZnS (II-VI) semiconductor quantum dots using fluorescence lifetime spectroscopy and complementary photoluminescence techniques. Fluorescence lifetime spectroscopy is used for the first time to provide real time information about growth and degradation mechanisms of nanomaterials in solution; b) studying the impact of surface modification of (II-IV) and (III-V) semiconductor quantum dots with ligands of increasing complexity on the nanomaterials’ overall stability in biological solutions; c) synthesis of metallic and metallic alloy nanomaterials and studying the impact of their composition, physical properties (size, shape) size and surface chemistry on their biological activity; d) synthesis and application of poly(lactic-co-glycolic) acid nanoparticles for targeted delivery of the tumor suppressor inhibitor, pifithrin-α, for the treatment of ischemic tissues, which are developed in progressive vascular diseases. This last project was recently funded by a University of Maryland School of Medicine, Baltimore, and University of Maryland Baltimore County (UMB-UMBC) joint fund to enable collaborative research between UMB and UMBC researchers.
Exploring Drug Diversity in Nucleic Acid Drug Design
The onset of resistance has limited the arsenal of chemotherapeutic agents that are available to combat bacterial, viral or parasitic infections as well as cancers. Consequently, there is an unmet medical need for the development of drugs aimed at combating resistant mutations. In an attempt to circumvent the problems associated with resistance, it is necessary to understand the factors that are involved in the interactions between enzymes and their substrates. As a possible solution to the on-going problem of resistance, we have designed a series of flexible nucleoside analogues called “fleximers” that have “split” the purine ring into its individual components; e.g. for forward fleximers the imidazole and pyrimidine rings have been split by a single carbon-carbon to allow for rotation of each subunit. This modification allows the nucleoside analogue to access more potential binding sites within the mutated enzyme. As a result, the inherent flexibility of the nucleosides endows them with the potential to circumvent mutations, thereby resulting in more powerful medicinal agents.
Chemistry/Biology Interface Program
The UMBC Chemistry/Biology Interface (CBI) program is an NIH supported program designed for those graduate students interested in pursuing cross-disciplinary training in the chemical and biological sciences. The program will prepare the students for the challenges of the 21st century, where those who possess multi-disciplinary training will have significant advantages. As more and more scientists pursue boundary-crossing lines of investigation, those researchers possessing multi-disciplinary skills will be increasingly in high demand. CBI students obtain their Ph.D. degree in chemistry, biology, biochemistry, molecular biology or chemical and biological engineering, but with an additional focus in one of the other disciplines. Each course of study is individually tailored to take into account the students’ strengths and interests, but all include coursework at an advanced level in both the biological sciences, chemistry and biochemistry.
Investigation of retrovirus assembly, structure, and genome packaging
Our laboratory is interested in understanding how retroviruses assemble, mature, and selectively package their RNA genomes. Nuclear magnetic resonance (NMR) and biophysical methods are primarily employed to study the structural and dynamic properties of viral constituents and their interactions under physiological-like conditions. Several retroviruses selected for our studies include human immunodeficiency virus type 1 and type 2 (HIV-1, HIV-2) and nonhuman pathogenic retroviruses like simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), murine leukemia virus (MLV), and rous sarcoma virus (RSV). In the long term, we would like to use the basic structural and functional information obtained to design new therapeutic approaches for the treatment of AIDS and other human diseases caused by retroviruses.
Computational and theoretical approaches to understand the functional properties of biochemical systems at multiple scales
Biological systems operate at a wide range of spatial and temporal regimes that typically span many orders of magnitude. Our research is focused on using computational and theoretical approaches to better understand how biological systems perform their functions across these disparate size and time scales. We model biological systems at differing levels of resolution in order to obtain a holistic and comprehensive description of their functional attributes. These efforts can include molecularly detailed descriptions of the physical and chemical properties of biomolecules as well as more coarse-grained numerical modeling of large-scale biochemical systems. By understanding the principles that underlie biological function, it should be possible to rationally modulate these functional properties for specific purposes. Our underlying objective is to use the knowledge gained in these efforts to provide tangible societal benefits. One such application is to determine the molecular basis for allosteric regulation of the polymerase from Hepatitis C virus, an important human pathogen. Another topic of interest is to realistically describe the biochemical pathways in microalgae responsible for generating large amounts of lipids that could ultimately serve as a sustainable and renewable fuel source.
Designer Biosensors – Developing Fundamental Guidelines Driven by Bioanalytical Applications
Biosensors promise to impact many fields ranging from basic research of biological systems to the development of biomedical devices poised to revolutionize modern healthcare. The number of methods for developing biosensors continues to grow at an impressive rate representing the cutting-edge interface of chemistry and many other fields. This talk takes a step back to understand the fundamentals of sensor performance of a class of electrochemical-based sensors. We utilize a combination of electrochemistry, biochemistry, and biomolecular design and engineering to build better biosensors. By developing models for the electrochemical response and understanding the structure and function of nucleic acids (e.g., aptamers) and proteins (e.g., ion channels) we can tune the response of a sensor based on the bioanalytical application of the sensor. Coupling these designer sensors with micro- and nanoscale electrodes further enables us to tune sensor performance for applications ranging from single-cell analysis to implantable devices for real-time therapeutic monitoring.