Chemistry and Biochemistry Faculty Projects



Chemistry 250px

Professor Justin Shearer overseeing student in chemistry project.

Characterization of the estrogen receptor ligand-binding domain

Professor Mark Brandt

The estrogen receptors interact with the "female" sex steroid hormones to regulate normal growth and development in both genders. In addition, the estrogen receptors are implicated in the initiation and growth of several types of tumors, of which breast cancer is the most common. Binding of ligand to the estrogen receptor is known to alter the shape of the protein in ways that alter its function. However, the details of this conformational change in the protein are incompletely understood. In order to examine these changes, we express the ligand-binding domain of the estrogen receptor in bacteria. The bacterial expression allows us to produce the protein in large quantities, and allows us to produce modified forms of the protein with novel properties. We then characterize interactions between the protein and both ligands and other small molecules. Methods used to probe the effects of these compounds on the protein structure include HPLC gel filtration chromatography and fluorescence spectroscopy. Work in the laboratory thus involves DNA manipulation and other molecular biological techniques for generating new mutant expression plasmids, protein purification techniques, and HPLC-based and fluorescence-based experiments for characterizing the estrogen receptor protein. In addition, we have been using molecular docking and molecular dynamics computer simulations to in in analyzing the experimental results and to help in planning additional experiments. The overall goal of the project is to understand the mechanisms by which this important protein has its effects, and possibly to allow generation of improved treatments for estrogen-dependent tumors.

New tools to fight drug-resistant breast cancer

Professor Ross Weatherman

One of the major challenges in treating breast cancer is that tumor cells eventually develop resistance to the drugs trying to treat them. My work focuses on synthesizing and testing new compounds specifically targeted to overcome resistance of breast cancer cells to tamoxifen, a common drug used to treat estrogen receptor-positive breast cancer. The projects will focus on the design and chemical synthesis of new compounds and new delivery methods, but will also include preclinical testing of compounds through binding and cell-based experiments. Some knowledge of organic chemistry is highly suggested.

Testing the full estrogenic signaling capabilities of potential endocrine disrupting chemicals

Professor Ross Weatherman

A major concern for the public is that there are compounds in the environment, either man-made or natural, that could be increasing the risk of the exposed population to hormone-related disorders such as cancer and diabetes. There are a number of these "endocrine disruptors" believed to raise the risk of breast cancer, but full characterization of most of these compounds has not been performed. This project will use protein and cell-based assays to better characterize a number of these compounds and try to develop a more complete picture of the potential risk of these compounds. Some basic biology and chemistry experience would be useful, but not essential.

Sustainable Materials Laundry Tag

Professor Rebecca DeVasher

I have often wondered why frequently used materials don't have a "laundry tag" that includes pertinent information such as environmental footprint, proper use and disposal, and potential for reuse and recyclability. I envision this project to begin with collecting some information on commonly used industrial materials and conclude with a database that could be turned into a smart phone app. A student from any discipline can see how the world of chemistry can inform sustainable practices in industry.

Atlas of protein fold space

Professor Yosi Shibberu (MA)
Professor Mark Brandt (CHEM)
Professor Allen Holder (MA)
Professor David Goulet (MA)

Proteins play a key role in nearly all the biochemical process of life. A protein sequence (translated from its corresponding gene sequence in DNA) collapses into a tightly packed, 3D structure called a fold. We are interested in developing an atlas of all known protein folds. Such an atlas will aid in identifying the function of individual proteins and potentially lead to the design of proteins with new functions. An atlas is built by comparing all pairs of proteins from a large database.  Our pairwise comparison technique uses eigenvalues and eigenvectors and has proven to be efficient and accurate on sizable test sets.

Dimerization of the estrogen receptor protein

Professor Yosi Shibberu (MA)
Professor Mark Brandt (CHEM)
Professor Allen Holder (MA)
Professor David Goulet (MA)

The estrogen receptor protein is the drug target of tamoxifen, one of the most successful drugs for treating breast cancer. We are interested in computer simulations of this protein to better understand how it functions. Some of our simulations have required more than a month of computation on the mathematics department's 48-core workstation. Each simulation generates several gigabytes of data to analyze. The project has important implications for both breast cancer research and for modeling protein-protein and protein-small molecule interactions.

Probing 8-Hydroxy-2'-Deoxyguanosine as a marker of oxidative DNA damage

Professor Daniel Morris

Nucleoside derivatives, especially those that are guanosine-based, are important markers for diagnosing and/or monitoring serious diseases and clinical conditions.  These markers include several methylated guanosine derivatives associated with thyroid cancer and the ubiquitous oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OH-dG).  With the exclusion of ionizing radiation, oxidative DNA damage is associated with the metal-dependent decomposition of H2O2 and subsequent generation of reactive oxygen species (ROS).  Oxidative damage to DNA appears to be very selective with the guanosine-based derivative 8-OH-dG increasing substantially over background levels.  Evidence suggests that DNA has the capability of binding metal ions, and reaction of H2O2 at or close to the site of metal binding would account for the selective nature of oxidative damage.  Given the variety of sites in DNA to which metal ions can bind (phosphate groups vs. different positions on individual bases), questions arise regarding the relationship between DNA binding sites and production of modified nucleosides.  We study the interactions of metal ions with the calf thymus DNA (CT-DNA) and probe the ability of the metal ion/H2O2 systems to produce 8-OH-dG.  Our current work focuses on the ability of selenium compounds to act as both anti- and pro-oxidants for metal ion mediated oxidative damage. The mechanism by which inorganic selenium compounds decrease metal ion-mediated oxidative damage is reported to involve metal ion coordination. We perform experiments in which the selenium compounds are added to DNA before (Condition 1) and after (Condition 2) the metal ions to determine if the selenium compounds are limited to coordinating only free metal ions in solution or if they are capable of competing effectively with DNA for these metal ions.  Understanding the mechanisms behind the observed antioxidant and pro-oxidant activity of compounds is an important goal in the treatment and prevention of many diseases and clinical conditions.

Synthesis and applications of carbon cryogels in environmental science and separations

Professor Justin W. Shearer

Carbon cryogels are a unique form of carbonaceous media that are characterized by being greater than 60% porous and containing micropores and mesopores.  There are several projects in which carbon cryogels are being synthesized and used in separation science and environmental chemistry:

  1. The design of uniformly sized carbon microspheres is attractive in the field of analytical separations.  In order to synthesize carbon microspheres, a mixture of microfabrication and wet chemistry can be employed.  Carbon microspheres can be used as material to be packed into high-performance liquid chromatography columns and tested for the quantitative analysis of many classes of environmental contaminants.
  2. Monolithic materials are also quite attractive in the field of separation science, as the diffusion of peaks in a chromatographic analysis due to mass transport can be minimized.  The synthetic pathway to obtaining carbon cryogels also lends to the fabrication of carbon monoliths.  Carbon monoliths can be used in chromatographic separations and extraction studies to quantifiy or remediate environmental contaminants.  It is also possible to perform electrochemical separations with carbon cryogels for heavy metal clean-up.
  3. Functional modification of carbon cryogels can also be accomplished by doping chemical species at specific points during the synthesis.  The ability to modify the functionality of a separation medium could lead to widespread application of the material in separations.

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