In addition to the regular curricular offerings, there are many research opportunities available to students throughout the year; we feel strongly that exposure to scientific research is very important and highly complementary to the training that our students receive in the classroom. We encourage all students to find a way a take part in a research experience during their years at Williams. During the fall and spring semesters, as well as Winter Study, students can undertake projects in faculty labs for academic credit (either as independent study or senior honors projects, or as a 3-week Winter Study course). During the summer months, students can work in faculty labs, typically for 10 weeks at a time; funding for summer research positions is obtained through individual faculty grants, as well as departmental and divisional sources. Students of all years are encouraged to talk to different faculty members about their research interests. Chemistry students have worked on biology, physics, mathematics, environmental science, and geoscience research projects on campus, as well as off-campus projects throughout the world.
To learn more about faculty research opportunities for students, please visit our faculty’s individual profiles.
Jimmy Blair, organic/bioorganic chemist
We need new antibiotics. Emerging drug-resistant bacteria pose a serious threat to public health, and while medicinal chemists constantly battle to develop antibiotics directed against these resistant strains, they still largely target the same molecular machinery as existing therapies. Histidine kinases are particularly attractive, yet untapped targets for new antibiotic development because they play central—and often essential—roles in controlling bacterial physiology. My multidisciplinary chemical biology laboratory approaches antibiotic drug discovery by integrating organic chemistry, biochemistry, and bacterial cell biology. We endeavor to develop small molecules targeting histidine kinases using the bacterium Caulobacter crescentus as our development platform. Histidine kinase-mediated signaling pathways are well conserved across bacterial species and are essential for virulence in many pathogenic strains, suggesting that discoveries in Caulobacter will lead to new antibacterial strategies effective against a broad-spectrum of bacteria. We target Caulobacter’s essential histidine kinases to assess whether pharmacological inhibition of these pathways provides a new antibacterial mechanism.
Anthony Carrasquillo, environmental/physical-organic chemist
Atmospheric particulate matter, or aerosol particles, have important implications for human health, visibility, and the global climate. Our ability to accurately predict ambient concentrations, chemical composition, and relevant properties (e.g., optical properties, toxicity, cloud forming potential, etc.) is limited primarily due to significant gaps in our understanding of how the organic aerosol fraction forms and evolves over time. Organic aerosol is immensely complex, containing hundreds to thousands of individual molecules, each with their own chemical properties and reactivities. Even the most carefully executed laboratory experiments and sophisticated models are unable to produce material with a chemical composition similar to that of the organic aerosol measured in the atmosphere, yielding quite possibly the biggest open question in atmospheric (or environmental) chemistry. In my research group we will address this significant knowledge gap by taking a multi-phase approach, studying the radical oxidation pathways occurring within three fundamentally distinct atmospheric molecular environments: the gas, organic aerosol, and aqueous phases. Student researchers will draw on techniques from across all areas of chemistry, utilizing a combination of organic synthesis, advanced chromatography, mass spectrometry, spectroscopy, and kinetic modeling to identify the major chemical mechanisms responsible for the formation and chemical evolution of organic aerosol particles.
Amy Gehring, biochemist
If you have smelled fresh dirt, you have already been introduced to bacteria of the genus Streptomyces. In addition to producing the characteristic odor of dirt, these common soil bacteria manufacture the majority of known antibiotics. These medicinally important compounds are produced during the course of the bacterium’s unusual and complicated life cycle that culminates in sporulation. Research in my lab involves understanding the regulation of this developmental process and concurrent antibiotic production in the model organism Streptomyces coelicolor. Beginning with mutant strains that are defective in certain aspects of development, we have identified genes and thereby proteins that are necessary to progress through the various stages of the bacterium’s life cycle. Current projects in the lab include (1) using proteomics approaches including 2D gel electrophoresis and MALDI-TOF mass spectrometry to characterize changes in the cell resulting from activity of a stress response sigma factor; (2) characterizing the activity of a potential transcription factor required for sporulation; and (3) assaying the effects of various mutations on antibiotic production.
Christopher Goh, inorganic/polymer chemist
Metal-based catalysis can be found in many crucial biochemical and chemical processes. Taking advantage of these catalytic reactions as starting points, our group aims to discover new catalysts or to improve the efficiency of existing systems. A research problem in my group starts with an exploration of the variable space of a catalytic system. We examine the factors that influence the performance and hypothesize strategies for improving the catalyst, and probe these ideas by modifying catalyst compositions. One current project involves the synthesis and application of copper based atom transfer radical polymerization (ATRP) catalysts. These catalysts provide the power to dictate the composition, molecular weight and molecular weight distribution of macromolecules, and to precisely control their architecture. Thus, such catalysts have a multitude of applications in designing new materials for packaging, automotive, and medical industries for example. A second project centers on the discovery of homogeneous iron catalysts for the oxidation of fatty acids and their derivatives. Fatty acids can be obtained from plant oils and represent a renewable resource for the polymer industry. The metal catalyzed oxidation of this class of compounds is of interest in the formation of resins, an industrially important class of compounds.
Sarah Goh, organic/polymer chemist
Our research investigates non-covalent assemblies based on biological system through: development of self-assembled hydrogels by integrating synthetic polymer and protein-mimetic components, resulting in materials with tunable properties and function; advancement of enzymatic polymerization methodologies for the preparation of functional polymers by exploring active site geometries through genetic engineering; and evaluation of protein- and polysaccharide-based platforms for the targeted placement of active nano-catalyst centers in order to control macroscale function and architecture of these assemblies.
Kathryn Hart, biochemist
We are engaged in an arms race with pathogens. And we’re losing. Just as quickly as we can develop new antibiotics or antiviral treatments, resistant strains emerge – often within the year. Evolution, it turns out, doesn’t always take eons. In fact, we are watching microbes evolve in real time in clinics, on farms and in the natural environment, which gives us the opportunity to both study how evolution occurs on short timescales and learn how to combat drug resistance. My lab studies how drug resistance evolves at the molecular level with a particular focus on protein stability. Many forms of drug resistance depend upon a small number of mutations that result in changes to a protein’s amino acid sequence. By investigating how these changes affect protein structure, stability and function, we can begin to understand how evolution works at the molecular level and leverage these insights to inform the design and implementation of new drug treatments. Current projects in the lab investigate drug resistant mutations in β-lactamase, an enzyme critical for antibiotic resistance in bacteria, and HIV protease, an enzyme targeted by antiretroviral therapies using biophysical techniques (circular dichroism, UV-vis and fluorescence spectroscopies) and microbiology techniques (cell growth competitions, minimum inhibitory concentration measurements, screen development).
Lawrence Kaplan, Emeritus
DNA is packaged in the cell nucleus by wrapping around basic proteins called histones. The histone/DNA complex is called chromatin. Most chromatin consists of histones H2A, H2B, H3, H4 and a linker histone H1. The erythrocytes in mammals do not have a nucleus and therefore have no net protein or DNA synthesis. Amphibians and avians do have a nucleus but the genetic apparatus is shutdown, presumably by the presence of the linker histone H5. We are studying the role that H5 plays in the control of replication and transcription by studying the relative binding affinity of H5 compared to H1. Thermal denaturation curves and isothermal titration calorimetry are the primary tools being used to study the binding affinity of the linker histones.
Charles Lovett, Emeritus
DNA damage by agents in the environment poses a constant threat to the survival of all organisms. In order to maintain the integrity of their genetic material, cells respond to such damage by activating, or inducing, a large repertory of enzymes that repair DNA and otherwise provide for cellular survival. Exposure of bacteria to DNA damaging agents results in the induction of a diverse set of physiological responses, collectively called the SOS response, which include enhanced capacity for recombinational repair, enhanced capacity for excision repair, enhanced mutagenesis, prophage induction, and inhibition of cell division. The research in our laboratory focuses on the SOS response in the bacterium Bacillus subtilis, a close cousin of the anthrax bacterium. Using a genomic screen, coupled with biochemical studies and microarray analyses, we have identified about forty genes that comprise the B. subtilis SOS response. Using a combination of genetic, proteomic, and biochemical analyses we are trying to understand how the integrated activities of the SOS gene products provide for the cell’s response to DNA damage.
Lee Park, inorganic chemist
I am interested in various aspects of molecular self-assembly. Our major area of study is in the realm of organic solar cells: we are using various approaches to control the morphology that develops in the polymer blend layer (which is responsible for the absorption of light) in bulk heterojunction solar cells. Some approaches involve generating surface patterns (via microcontact printing, edge-spreading lithography…), while others involve derivatization of the parent polymers in order to promote self-assembly of the components of the polymer blend film into structures that will give rise to more efficient solar cells. We are currently exploring the use of fluorocarbon-hydrocarbon interactions as a means of influencing the morphology that develops in the active layer. Another area of interest in our lab involves the design of new liquid crystalline materials, in which small discrete molecules form one-dimensionally aligned structures (which might find application as one-dimensional conductors for instance) due to various intermolecular interactions, such as hydrogen bonding or donor-acceptor interactions. Students in my lab do a combination of synthetic work, physical characterization of compounds prepared, and evaluation of those new materials in the context of actual working devices (solar cells).
Enrique Peacock-López, physical chemist
A large number of biochemical systems show regulatory feedback mechanistic steps either at the cellular level, like in the HIV-Rev protein, or at the physiological level, like in the hypothalamous-pituitary-adrenal hormonal system. Our group has been studying the molecular basis of different chemical, biochemical and physiological mechanisms and has proposed several dynamic models to explain observed temporal and chaotic oscillation in the concentrations of relevant metabolites. We have concentrated most of our effort in understanding chemical self-replication, where several chemical systems have been designed experimentally. For example, oligonucleotides have been considered by von Kiedrowski’s, Orgel’s and Nicolau’s groups, and peptides have been studied by Gadhiri’s and Chmielewski’s groups. More recently Joyce’s group designed a self-replicating and a cross-catalytic self-replicating ribozymes, which may be better suited for Darwiniam evolution than the oligonucleotide or peptide systems. In the case of cross-catalytic mechanisms, we have considered the dynamics of competitive systems and mutualistic hypercycles. We also continue studying and modeling the transport of incompletely spliced mRNAs across the nuclear membrane, which is regulated by HIV-Rev protein, and we have studied the behavior of an insect-predator-ant system, and we want to develop mathematical models that we will allow us to improve our understanding of species competition and coexistence.
Bob Rawle, biochemist
The recent emergence of deadly viruses such as Ebola, Zika, and swine flu has highlighted the need to better understand viral infection at a molecular level to prevent and treat viral disease. Broadly speaking, my lab is interested in asking fundamental biophysical questions about two essential steps in viral infection – binding to the host cell membrane and membrane fusion/penetration. As an initial model system, we are studying Sendai virus, a member of the paramyxovirus family which includes measles and human parainfluenza viruses. To study Sendai virus, we observe individual viruses binding and fusing with host cell membrane mimics called model lipid membranes. These model lipid membranes are lipid bilayers self-assembled inside a microfluidic device, and they enable us to simplify the complex host cell environment to just a few components. This allows us to ask direct questions about key molecular interactions. To perform these biophysical studies, researchers in my lab use a variety of techniques including fluorescence microscopy, microfluidics, surface chemistry, kinetic modeling, single molecule fluorescence, and quantitative image analysis. We are also interested in model lipid membranes themselves, and other projects in the lab involve the development and study of model membrane systems, with implications for drug delivery, biosensors, and membrane biophysics.
David Richardson, organic chemist
Nature is a superb organic chemist. While taking care of the day-to-day business of being alive, living systems deftly assemble organic molecules of incredible complexity and subtle beauty. Among other topics, my research involves synthesis, isolation and characterization of naturally-occurring substances, particularly those with interesting biological activity. Current areas of study involve antibiotic agents from Southeast Asian plants, allelopathic agents from local plants, the analysis of PCB contamination in the Hoosic River watershed, synthesis of selectively deuterated, low molecular weight fluorocarbons, and the analysis of heterocylic organic molecules by 15N-NMR spectroscopy.
Anne Skinner, Emerita
My lab works at the interface between chemistry and two other disciplines, geology and archaeology. One way to determine the age of materials is to look at the damage caused by radioisotopes in the material and its surroundings. The older the object, the more damage should be found. The extent of damage can be measured with electron spin resonance (ESR), a technique that looks at the unpaired electrons created when a stable bond is broken by radiation. Projects in the past few years have included determining Late Stone Age dates at Olduvai Gorge, clarifying the transition from Neanderthals to Homo sapiens in Central Europe, and discovering the use of fire in South Africa 1.5 million years ago. Current projects are taken from sites in India, Brazil, Africa, and Europe.
Thomas E. Smith, organic chemist
My research interests lie within the broad category of organic synthesis that impacts such areas as biology, pharmacology, materials science, and reaction mechanism. My current focus is on the development of new methods for increased efficiency in organic synthesis and their application to molecules of biological significance. Organotransition metal systems, in particular, are utilized extensively in this endeavor due to their versatile selectivity profiles and catalytic possibilities. In one project, we are exploring a general asymmetric synthesis of the kavalactones. These natural products are the biologically active constituents of kava root, which has been used ceremonially in South Pacific cultures for centuries and has attracted recent attention in the Western world as an “alternative” anti-anxiety remedy. We are also investigating the asymmetric total synthesis of the myxobacterial antibiotic, jerangolid D, wherein both the ?-lactone and cis-dihydropyran rings are assembled using an extension of the methods developed for the kavalactone syntheses. In another project we are probing the scope and limitations of a new method for the thermodynamic deprotonation of readily available heterocyclic systems, thus allowing for the assembly of more complex molecular architectures from simple building blocks. This technique was successfully applied to a novel synthesis of the antiviral marine natural product, hennoxazole A. Studies on other complex pyran-based anticancer natural products such as enigmazole A, tedanolide C, and aplyronine are currently underway.
Jay Thoman, physical chemist
Inter- and intramolecular forces help determine the shape and behavior of molecules. Using the gas-phase fire-suppressant molecules known as hydrofluorocarbons (HFCs) as model systems, my colleagues and I use laser spectroscopic techniques to probe the vibrational overtones of CH stretches and to learn about molecular structure and dynamics. We use ab initio computational chemistry to model these vibrations, and their impact on atmospheric chemistry. Working with Dave Richardson, we synthesize deuterated fluorocarbons; these isotopically substituted HFCs are used to test theories of hydrogen bonding and energy transfer. The local environment provides many chemical research opportunities. Using the resources of the Environmental Analysis Laboratory on campus, I have collaborated on projects including studies of: lead in urban soils, perchlorate ions in drinking water, PCBs in the Hoosic River, and heavy metals in fish taken from local ponds.