Lila Manstein and Bailey Plaman will be presenting. Lila is working with Professor Patricia O'Hara, and Bailey is working with Professor Anthony Bishop.
Lila Manstein will discuss “Nutraceuticals: A Study of Antioxidants in Food”. In chemistry, oxidants react with other species by removing electrons. Biologically, oxidants are generated during normal biological functioning of a cell or organ at low concentrations and at higher concentrations during a pathological or diseased state. These molecules, generically called Reactive Oxygen Species (ROS), are free radical oxygen-containing molecules and are very reactive. Fortunately, there are other species in the body known as antioxidants that can decrease the concentrations of ROS by one of several methods. In the simplest method, the antioxidant sacrifices itself by donating an electron, reducing the ROS and thereby protecting other biological molecules such as proteins, fats, and DNA. In another model, the antioxidants turn on or off signaling systems responsible for the production of ROS. Polyphenols are common class of antioxidants found in many foods such as wine and olive oil. The goal of my research project is to create a simple quantitative means for consumers to measure the polyphenol content in foods such as olive oil. One assay I have explored is a chemical reaction that results in a bathochromic shift on the absorbance peak of a reporter dye when exposed to an antioxidant. In this assay, a ferric ferricyanide dye solution that is made by mixing ferric chloride and potassium ferricyanide. In the presence of antioxidants (reducing agents), the peak absorption of the dye shifts from 440 nm to approximately 700 nm. Visibly, the solution turns from a dull brown to brilliant blue color known as Prussian Blue. The exact wavelength and the intensity depend not only on the quantity, but also upon the antioxidant tested. I hope to further characterize this reaction and to use this information to develop a reliable tool that uses visible photochemistry for non-scientists to measure the polyphenols in food.
Bailey Plaman will discuss “Biarsenical Small Molecule Activation of Engineered Kinase Interaction Motif (KIM) Family Protein Tyrosine Phosphatases (PTPs)”. Protein tyrosine phosphatases (PTPs) are a large class of enzymes that catalyze the cleavage of phosphate groups from phosphorylated tyrosine residues of proteins. Since dephosphorylation is a critical regulatory method for cell signaling, the human genome codes for a large variety of PTPs that serve distinct roles in diverse signaling pathways. Dysregulation in PTP signaling pathways often results in disease, which makes PTPs an attractive target from a pharmaceutical standpoint. Although the structure and function of PTPs vary greatly, the protein sequence of the catalytic site is highly conserved, making it difficult to create small-molecule ligands that specifically target individual PTPs. As a result, the cellular function of most PTPs remains poorly understood. We aim to develop a strategy to specifically activate PTPs to better understand their function within the cell and the consequences of their dysregulation. To do so, we genetically engineer PTPs to be susceptible for biarsenical small molecule activation. To make the method generalizable to all PTPs, we introduce three cysteine point mutations to the highly conserved WPD loop motif. Biarsenical small molecules bind specifically to the cysteine-rich region to activate only mutant PTPs. Previous experiments from the Bishop lab showed promising results for the target-specific activation of hematopoietic protein tyrosine phosphatase (HePTP) using this strategy. My project uses the same activation strategy to determine whether the success with HePTP, a member of the kinase interaction motif (KIM) family of PTPs, is common to the other two members of the family: striatal enriched protein tyrosine phosphatase (STEP) and Protein Tyrosine Phosphatase Receptor Type R (PTPRR). KIM-family PTPs are generally thought to play a role in memory and learning, so success with activation strategies could provide important tools to better understand neurodegenerative disease.