REU Projects

Faculty Mentors: John Asbury and Ray Schaak

Project Description: A central problem in the development of solar power as an alternative energy supply is the ability to store the energy for later use when the sun is not shining. Catalytic materials based on inexpensive and earth-abundant elements are attractive alternatives to noble metal and rare-earth catalysts. This REU project will work toward development of new earth abundant nanocrystalline materials systems that enable high efficiency photocatalysts for hydrogen production and oxygen evolution. This REU project will involve use of inorganic solution chemistry methods to synthesize novel metal-phosphide catalysts with a variety of structures. These catalysts will be coupled to light absorbing copper-zinc-tin-sulfide nanocrystals to combine light harvesting and catalysis together in the same system. A variety of materials characterization methods (TEM, XRD, FTIR, UV-Vis, and TGA/DSC) and time-resolved spectroscopies will be used to examine photocatalytic reactions at the catalyst surfaces. The corresponding surface chemistry and photocatalytic activity will be characterized by monitoring the evolution of hydrogen and oxygen gases.

Faculty Mentor: Philip Bevilacqua

Project Description: It is well known that protein enzymes catalyze a diverse array of chemical reactions with exceptional rates and specificity. RNA is comprised of only four similar nitrogenous heterocycles, yet it too can catalyze chemical reactions and do so with remarkable rate acceleration and specificity. The surprising discovery that RNA can catalyze reactions is relatively recent and led to the Nobel Prize in Chemistry in 1989. Moreover, because RNA can also store genetic information, the notion of an RNA World in which RNA, or a related polymer, was key to the emergence of life has been advanced. This project will employ interdisciplinary approaches to understand how RNA catalyzes reactions. Students will be engaged in a combination of molecular biology, chemical kinetics, and bioanalytical techniques. In addition, there is the option to study chemical reactions that may have formed the first RNAs that were then copied to begin life.

Faculty Mentor: Amie Boal

Project Description: Ribonucleotide reductase (RNR) enzymes, required in all organisms for DNA replication and repair, are important targets for development of new antibiotics. All RNRs share a common nucleotide reduction mechanism, initiated in the catalytic α subunit by a cysteine (Cys) thiyl radical. Evolution has diversified RNR into three known classes, I-III. Within class I, found in humans and many pathogenic bacteria, five subclasses, a-e, have been reported.  These enzymes use remarkably varied inorganic chemistry in a separate β subunit to generate the catalytic thiyl radical transiently on each turnover. The diverse radical-initiation strategies in class I allow pathogens to adapt to deprivation of specific transition metals by their hosts. We seek to understand the distinct chemistries of the host and pathogen enzymes using x-ray crystallographic, biochemical, and spectroscopic approaches. These efforts have allowed us to discover several new class I RNR metallocofactors and assembly mechanisms, with the eventual goal of targeted inhibition of these pathways in bacterial infections.

Faculty Mentor: David Boehr

Project Description: RNA viruses, including Zika, hepatitis C and poliovirus, cause a number of acute and chronic diseases. These viruses hijack host cell membranes to create their own replication organelles to facilitate virus replication and help protect from host immune response. We are using solution-state NMR and other biophysical techniques to understand the interactions between viral proteins and replication membranes and to delineate the mechanisms by which membrane association affects viral protein structure and function. These interactions might also be potential targets for new anti-viral drugs. REU students on this project will learn state-of-the-art, high-dimensional NMR techniques as they pertain to understanding protein structure and dynamics. These NMR methods will be complemented by other spectroscopic and calorimetric methods, along with other biochemical and molecular biology techniques.

Faculty Mentors: Squire Booker, Carsten Krebs, Alexey Silakov, and Amie Boal

Project Description: Enzymes within the radical S-adenosylmethionine (SAM) superfamily catalyze a dazzling array of chemical transformations that proceed via free radical intermediates. Radical SAM (RS) enzymes use radicals derived from SAM to initiate catalysis by abstracting hydrogen atoms from their respective substrates. This project will focus on developing methods to annotate the functions of RS enzymes catalyzing unknown reactions. Students will learn how to generate sequence similarity and genome neighborhood networks to provide insight into function via 9 bioinformatics methods. They will also learn molecular biological techniques, such as cloning and site directed mutagenesis and gene expression. Lastly, they will learn how to purify and manipulate these oxygen-sensitive proteins under anaerobic conditions and characterize them using UVvis, EPR, ENDOR, HYSCORE and Mössbauer spectroscopies, x-ray crystallography and techniques.

Faculty Mentor: Joseph Cotruvo

Project Description: Rare earth elements (the lanthanides, yttrium, and scandium) are critical materials for numerous contemporary technologies but accessing and separating them is a major scientific challenge. Recent discoveries have shown that certain bacteria require lanthanides for specific biological functions. A more thorough understanding of the chemistry and biology underlying selective lanthanide acquisition, trafficking, and utilization by these organisms has the potential to lead to new bioengineering methods for rare earth capture. The Cotruvo lab has discovered several lanthanide-binding proteins, including “lanmodulin.” Lanmodulin undergoes a large conformational change from a disordered to an ordered state in the presence of rare earth elements, with almost one billion-fold selectivity over more abundant metals. This project aims to understand the mechanism of this conformational change and its enormous selectivity for rare earths. Students will use multiple biochemical and biophysical methods, including molecular biology, protein purification, fluorescence spectroscopy, and NMR spectroscopy, and apply knowledge gained to re-engineer the protein to bind other desirable metals.

Faculty Mentor: Paul S. Cremer

Project Description: Phosphatidylserine and phosphatidylethanolamine lipid headgroups both contain amine moieties that can bind tightly to first row transition metal cations like Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺. In the presence of an oxidant, such as hydrogen peroxide, redox active cations like Cu²⁺ will catalyze the generation of hydroxyl radicals. This can lead to the oxidation of membrane double bonds through a combination of the Fenton and Haber Weiss reactions. Such oxidative damage ultimately leads to the lysis of the membrane and may be associated with neurodegenerative diseases like Alzheimer’s and Parkinson’s as well as developmental disorders like autism. Oxidative damage is more likely to occur in vivo when the concentration of metal ions is no longer tightly regulated (i.e. metal ion dyshomeostasis).  An REU student working on this project will get the opportunity to explore membrane oxidation chemistry as a function of the lipid headgroup identity, the charge on the membrane, and the positions of double bonds. Specifically, the REU student will learn to use microfluidic platforms and fluorescence microscopy to explore the kinetics of membrane oxidation. Skills will be taught concerning the fabrication of microfluidic devices and supported membranes, the use of fluorescence recovery after photobleaching (FRAP), and the making of kinetics measurements at interfaces.

Faculty Mentor: Paul S. Cremer

Project Description: Cations and anions are electrostatically attracted to one another in the gas phase or in a salt lattice. In aqueous solution, this attractive force is attenuated by water hydration shells around each ion that must be partially shed for the ions to interact with one another. Such hydrated ion interactions are ubiquitous in environmental and biochemical problems ranging from water treatment and ion exchange chromatography to the aggregation of proteins in diseased states. Some ions form contact pairs, while others involve intervening water molecules. This difference can have profound impacts on the chemistry of the system. The REU student will get an opportunity to understand and predict the types of interactions that can occur at the lipid membrane/water interface. Skills involving Langmuir monolayer formation, fluorescence microscopy, and vibrational spectroscopy will be taught. The goal of the project will be to understand how subtle changes in the surrounding environment can strongly impact the type and strength of ions pairs that are formed. These changes can, in turn, influence proteins binding, phase behavior, and even the taste of food.

Faculty Mentors: Paul Cremer, Ayusman Sen

Project Description: It has been found that receptor molecules, such as porphyrins, nanoparticles and proteins, can migrate up a concentration gradient of their corresponding ligands. This phenomenon, which is called chemotaxis, may have physiological consequences and can be exploited to create a new generation of nanomotors that respond to subtle changes in the chemical environment of the surrounding medium. We are exploring ligand-receptor binding systems to determine the underlying molecular mechanism of this process as well as to build a new generation of devices that can produce chromatographic separation of receptor materials. Significantly, many of the proteins that display chemotaxis are also enzyme-based catalysts wherein their ligand fuel may provide a direction of motion for the substrate. Students involved in this project will obtain a unique opportunity to study the motion of nanomaterials using novel spectroscopic techniques as well as help in the development of microfluidic platforms and assays.

Faculty Mentor: Beth Elacqua

Project Description: Compartmentalization is one of Nature’s design principles:  enzymes are ‘catalogued’ and can be shielded from reactive/incompatible environments or partitioned such that synergistic functions like catalysis are optimized. Generally, enzymes are attractive catalysts for synthetic organic transformations, yet, despite the emergence of highly-evolved biocatalysts, many are limited to the stepwise catalysis of naturally-occurring reactions and demonstrate markedly less selectivity in synthetic systems.  Artificially-constructed metalloenzymes continue to provide systems that are scalable for practical synthetic methods.  Although the diversity and complexity of natural systems is extraordinary, limitations on building blocks do exist, while synthetic systems equip chemists with unlimited functional building units to engineer robust materials.  Coupled with the continued development of supramolecular approaches to mediate self-assembly, synthetic approaches that comprise enzyme-like features are realizable. The Elacqua lab aims to develop Nature-inspired polymer nanoreactors that function in photo-controlled self-assembly and dual/tandem catalysis. The REU student would gain experience in organic and polymer synthesis, photochemistry, and catalysis, along with spectroscopic and light scattering techniques.

Faculty Mentor: Miriam Freedman

Project Description: Clouds in the lower atmosphere are composed of water, ice, or a mixture of these two phases of water.  Water droplets and ice particles are formed from nucleation on aerosol particles rather than from the condensation of water vapor.  The interactions of aerosol particles, clouds, and light are the greatest uncertainties in our understanding of the climate system.  This project focuses on the formation of ice particles.  Above temperatures of -40 degrees C, heterogeneous catalysts are required for ice to form, and the surface properties of these particles drive the ice nucleation process.  Our goal is to determine the properties of surfaces that promote ice nucleation.  We work with synthesized materials in which we can tune surface crystallinity, crystal structure, functional groups, defects, etc., to determine the role of each of these properties on the ice nucleation process.  Such work will allow us to create predictive models of atmospheric ice nucleation processes. 

Faculty Mentor: Ramesh Giri

Project Description: Alkenes serve as the most important feedstock for organic synthesis, having two vicinal sites for bond formation. Simultaneous construction of two carbon-carbon bonds across these vicinal positions is a most powerful strategy, providing modular, convergent and expedient routes to generate complex products from simple starting materials. This process is highly significant from a synthetic perspective due to its ability to reduce a multistep process to a one-step endeavor. Our research is focused on developing new concepts in alkene difunctionalization. Currently, we are developing concepts such as Synergistic Bimetallic Cationic Catalysis and Metallacycle Contraction Process to difunctionalize unactivated alkenes at both the classical 1,2-sites (vicinal) the alkenes occupy and the non-classical 1,3-sites (homovicinal). We also study mechanisms pertaining to these new reactions based on radical probes, organometallic synthesis, competition experiments and quantitative kinetic studies. The REU students will have opportunities to conduct cutting-edge research at the interface of organic and organometallic chemistry, develop new reactions to apply toward the synthesis of biologically important target molecules and natural products, and synthesize novel organometallic complexes as reaction intermediates to understand reaction mechanisms.

Faculty Mentor: Mark Hedglin

Project Description: Within the nucleus of every cell, our genetic information (i.e., genome) is encoded in strands of DNA that assemble into antiparallel, double helices.  Each time a cell divides, it’s genome must be faithfully copied for transfer to a daughter cell. DNA is a very reactive macromolecule housed within a reactive environment that is saturated with cellular metabolites and reactive oxygen species (ROS) that can alter or eliminate the coding properties of DNA through covalent modifications.  These damages can also result from exposure to environmental carcinogens such as ultraviolet radiation from sunlight and by-products from incomplete combustion of organic materials. Remarkably, humans have the remarkable ability to accurately replicate damaged DNA through a conserved process referred to as a DNA damage tolerance (DDT). This pathway relies on a highly-selective posttranslational modification (PTM) of a critical factor utilized throughout DNA replication.  Specifically, the Rad6/Rad18 complex covalently attaches a small protein (ubiquitin) to processivity sliding clamps (PCNA) encircling sites of DNA damage. Currently, it is unknown how this PTM is regulated and dysfunction is largely implicated in the onset and progression of cancer as well as resistance to chemotherapy.  In our lab, we develop various molecular probes to quantitatively monitor this PTM under in vivo scenarios and recent studies have provided unprecedented insight into various modes of regulation. This project will focus developing new molecular probes to characterize novel modes of regulation discovered in our lab.  Students will learn to how to dissect the structure and function of various human proteins to identify potential sites for modification with unique molecular probes.  Students will then learn molecular biology techniques (cloning, site-directed mutagenesis, gene expression, etc.), protein purification, and maleimide chemistry to manipulate and label human proteins with various fluorescent dyes (fluorescein, TAMRA, BODIPY, Cy3, Cy5, etc.). Finally, students will learn biochemical/biophysical techniques (FRET, fluorescence anisotropy, etc.) to characterize the effects of these fluorescent probes on the innate activities of the labeled proteins.

Faculty Mentor: Benjamin Lear

Project Description: Catalysis is the foundation of the modern chemical economy, allowing the accomplishment and commercialization of reactions that would otherwise be cost and energy prohibitive. The traditional means of increasing catalytic efficiency is to modify the catalyst to lower the barrier for any given specific reaction. The Lear laboratory’s approach is different: they modify the means by which heat is distributed to the catalyst. This REU project will focus on understanding how to use the properties of nanoparticles to control more precisely the distribution of this heat, attaining molecular-scale control in both time and space.  They then study the impact that this increased control has over the efficiency of catalyzed reactions. Students involved in this project will design and synthesize nanoparticle systems and characterize these systems using microscopy and diffraction techniques. They will then incorporate the nanoparticles into catalytically primed reaction mixtures and measure the efficacy of the photothermal effect for driving catalysis using a variety of analytical techniques.  The advantage of using such molecular-scale heat is that the thermal energy required to overcome reaction barriers is found only at the catalytic center and, thus, undesired chemical activity away from the catalyst remains inactivated. In addition, much higher temperatures can be realized when using localized heat, driving the reaction at significantly increased rates (billion-fold rate enhancements). Together, precise control over heat distribution increases both the activity and the selectivity of the catalyst / reaction mixture above that which can be realized using the more traditional bulk-scale heating. 

Faculty Mentor: Eric Nacsa

Project Description: The Nacsa group is focused on solving problems in synthetic organic chemistry. Our main projects leverage electrochemistry and related techniques to generate medicinally relevant structures from simple precursors in a single step.

Faculty Mentor: Will Noid

Project Description: Computational studies with atomically detailed models have contributed profound insight into molecular structure, dynamics, and interactions on the nano-scale.  However, many important phenomena occur on length- and time-scales that are inaccessible to atomically detailed simulations.  Consequently, lower-resolution "coarse-grained" (CG) models play an essential role in understanding phenomenon on meso- and macro-scales.  In this project, students will gain experience in developing and applying CG models that are not only exceedingly efficient, but also provide a remarkably accurate description of molecular structure and interactions.  Additionally, students may gain insight into how "generic" CG models can provide powerful, albeit qualitative, insight into the fundamental mechanisms driving many emergent phenomena.  Participating students can gain experience in rigorous statistical mechanical theories, software development for advanced computational methodologies, and state-of-the art molecular simulations.

Faculty Mentor: Ed O’Brien

Project Description: The specific activity of enzymes changes depending on the rate at which the ribosome synthesizes the enzyme during the elongation phase of translation. The molecular origins of this phenomenon is unknown, although a leading hypothesis is that translation kinetics alters cotranslational folding events that influence the population of soluble, but kinetically-trapped non-functional protein molecules. The goal of this project is to understand the extent to which protein structure around the active sites of enzymes can be perturbed by changes in codon translation rates. REU students working on this project will use in-silico coarse-grained models developed in the O’Brien Lab to simulate the synthesis of different enzymes, such as Luciferase and EgFABP1, that have been experimentally shown to exhibit altered specific activity. REU students will gain experience in computer coding, molecular dynamics simulations, and statistical and kinetic analyses of simulation trajectories. Ultimately, this work will help contribute to the emerging paradigm concerning how kinetics, in combination with thermodynamics, determines protein structure and function in cells. 

Faculty Mentor: Ray Schaak

Project Description: Catalysts can facilitate chemical reactions that otherwise would be kinetically and/or economically prohibitive. The discovery of new catalysts can therefore enable new types of reactions and also improve the efficiency and/or selectivity of existing reactions, which in turn can lead to new applications. In this project, REU students will engage in multi-disciplinary efforts to discover new heterogeneous catalysts that are relevant to applications in solar energy conversion, fuel cells, and target-oriented organic synthesis. Representative types of catalytic transformations include the oxygen evolution reaction, the oxygen reduction reaction, CO₂ reduction, and selective hydrogenations and oxidations. Students will first synthesize a variety of solid-state materials as nanoparticles, films, powders, and single crystals, and then analyze them using a suite of materials characterization and catalytic testing techniques. Inspiration for target catalytic materials will be drawn from computational and mechanistic predictions, as well as from structural and compositional analogies with known homogeneous and biological catalysts.

Faculty Mentor: Ayusman Sen

Project Description: Self-powered nano and microscale moving systems are currently the subject of intense interest due in part to their potential applications in nanomachinery, nanoscale assembly, robotics, fluidics, and chemical/biochemical sensing. REU projects will involve the design, characterization, and study of autonomous, chemically powered, particles. One of the projects will involve the fabrication of Janus particles and the examination of their movement arising from reactions occurring at the two faces. The second project will involve the synthesis of enzyme-anchored particles powered by catalytic reactions and the study of their collective behavior in the presence of external and internal stimuli. Such systems can be further configured to observe predator-prey behavior among the swimmers, where groups of particles functionalized with different enzymes will form interaction cascades and display emergent dynamic patterns. The projects will expose the REU students to a variety of synthesis and materials characterization techniques. More broadly, the students will learn how chemistry, physics, nanotechnology, and fluid dynamics can be integrated to create synthetic materials that exhibit unprecedented biologically-inspired behavior.

Faculty Mentor: Alexey Silakov

Project Description: Metalloenzymes catalyze a wide variety of difficult reactions that, in a majority of cases, require a chain of chemical transformations. The Silakov group is interested in a novel hybrid class of metalloenzymes containing two catalytically active domains: a hydrogen-utilizing [Fe-Fe] hydrogenase and a rubrerythrin. It is hypothesized that hydrogen is heterolytically cleaved by the [Fe-Fe] hydrogenase domain to provide electrons and protons, which in turn are used by the di-iron site of rubrerythrin to reduce hydrogen peroxide to water. This REU project will focus on understanding the interaction between the two domains by means of trapping and characterizing intermediates in the reaction. REU students will learn to overexpress and isolate metalloenzymes, perform rapid-freeze quench experiments and characterize intermediates by electron paramagnetic resonance (EPR) and/or fourier-transform infrared spectroscopies. Students will also be provided with an opportunity to perform theoretical modeling of the experimental data using EPR simulation software and perform density functional theory calculations.

Faculty Mentor: Emily Weinert

Project Description: Oxygen (O₂) is an important environmental signal that must be sensed by bacteria, due to its key role in respiration for aerobic and facultative anaerobic bacteria, as well as its toxicity to obligate anaerobes. O₂ levels also vary significantly within the environment and the human host, serving as a signal for bacteria to alter growth phenotypes and virulence. Therefore, it is important to understand the sensing and signaling mechanisms that allow bacteria to respond to changes in O₂ levels. A family of heme proteins, termed globin coupled sensors (GCSs), regulates diverse functions in response to O₂ levels, such as aerotaxis and cyclic-di-GMP synthesis. Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that is synthesized by diguanylate cyclase enzymes and controls important bacterial processes such as biofilm formation, host colonization, and virulence. The aim of this project is to elucidate the mechanism of O₂-dependent GCS cyclase activation and downstream pathways controlled by GCS signaling. REU students will gain experience in protein expression and purification, enzyme kinetics, and heme spectroscopy, as well as microbiological assays to test the effects of GCS activation and signaling in vivo. 

Faculty Mentor: Lauren Zarzar

Project Description: This project will focus on studying and quantifying the active motion of droplets in solution. Microscale oil droplets can move in water and interact with each other through chemical gradients. We will be developing methods to quantify that motion and the forces on the droplets and how that correlates to the chemical gradients. This project will involve both experimental components, such as droplet fabrication and optical microscopy, and also image analysis. 

Faculty Mentor: Bert Chandler

Project Description: Our lab focuses on developing new solid phase materials to catalyze a wide variety of reactions.  We are especially interested in industrially important reactions and in developing new chemistries for energy conversion and storage.  Some examples include: (i) synthesizing and characterizing new materials; (ii) monitoring and quantifying hydrogen adsorption on new energy storage materials; (iii) preparing and studying catalytic reactivity of nanoparticle catalysts; (iv) understanding how electron donating and withdrawing groups affect adsorption and catalytic activity (v) learning how to control the surface acid-base chemistry of metal oxides; (vi) using infrared spectroscopy to monitor intermediates during catalytic reactions.  We are interested in adding students with a wide range of expertise, from first-years to rising seniors.  If you have completed at least a year of college chemistry and Calc I, and are excited about learning what research is like, we have projects available for you. 

Faculty Mentor: Ruobo Zhou

Project Description: The Zhou lab is dedicated to advancing the field of biological research through the development and application of innovative imaging-based techniques. Our primary focus is on unraveling the intricate compartmentalization and spatiotemporal organization of crucial protein-protein and protein-RNA interactions that underpin fundamental cellular processes and their relevance to human diseases. Our laboratory harnesses a wide spectrum of cutting-edge imaging techniques to dissect disease-related biological systems, including 1) Single-Molecule Detection Techniques: These precision methods allow us to probe individual molecules, revealing insights into their behavior and interactions; 2) Multi-Color Super-Resolution Fluorescence Nanoscopy:Techniques like Stochastic Optical Reconstruction Microscopy (STORM) empower us to visualize biological structures and biomolecular interactions at unprecedented spatial resolution, providing a new level of detail; 3) Omics Approaches: We employ mass spectrometry-based proteomic analysis and transcriptome-scale RNA imaging technique to comprehensively profile biomolecular content at the molecular, cellular, and tissue levels. Our multidisciplinary approach and the wide array of cutting-edge tools we employ enable us to delve deep into the complexities of these biological systems, fostering a deeper understanding of their fundamental mechanisms and their implications for human health and disease. Through our research, we aspire to make meaningful contributions to the fields of molecular biology, cell biology, neurobiology, cancer biology, and biomedicine.