Chemistry Chemistry Seminar - Thesis Student Presentations

Presenters: Sara Jinee Buck (Bishop Lab), Laboni Hoque (Leung/Marshall Lab), and Dominique Iaccarino (Martini Lab, Geology)

Sara Buck: Seminar Title: "Inhibition of Protein-Tyrosine Phosphatases (PTPs) by Chemically-Induced Dimerization." Abstract - Many signaling pathways are regulated via the phosphorylation of tyrosine residues. Protein tyrosine phosphatases (PTPs) are a super-family of enzymes—more than 100 encoded in the human genome—responsible for dephosphorylating proteins. PTPs function in coordination with phosphorylating protein tyrosine kinases (PTKs) to help control these signaling pathways.
Abnormal tyrosine phosphorylation has been linked to diseases such as cancer and autoimmune disorders. Pharmaceuticals have found lots of well-characterized small molecule inhibitors for kinases, but have not been as successful targeting specific PTP molecules due to a highly conserved active site found across the PTP family. However, a protein known as Shp2, a sub-family of PTPs, might be able to inhibit the PTP active site. In its basal state, Shp2 displays autoinhibition in which its N-terminus domain, N-SH2, gets wedged into the active site and prevents substrates from binding. Recent studies have shown the N-SH2 domain can be removed, expressed independently, and still exhibit an inhibitory function. Since the PTP domain is highly conserved, this suggests that perhaps the inhibitory interaction between the N-SH2 domain and the PTP domain is not specific, but a result of proximity and if so, the isolated N-SH2 domain may be able to inhibit other PTPs. To recreate proximity, a tool known as chemically induced dimerization can be used to fuse protein modules to proteins of interest with the help of a bifunctional molecule. By testing the proximity effects of the N-SH2 domain, we will gain insight into generating inhibitory tools to control PTP activity.

Laboni Hoque: Seminar Title: "Structure Determination of the 2-Chloro-1,1-Difluoroethylene-HCl Complex Using Microwave Spectroscopy." Abstract - Intermolecular interactions, although much weaker than covalent or ionic bonds, are ubiquitous, and when aggregated in large molecules, these interactions have significant consequences on chemical and biological systems. Since these forces are often difficult to observe under normal conditions, as their relative weakness results in constant breaking and reforming of intermolecular bonds at room temperature, they must be studied in isolation in molecular complexes comprised primarily of van der Waals forces. The Leung/Marshall labs explore these interactions, specifically in the model system of haloethylenes in complex with protic acids of varying strength (HF, HCl, and HCCH). These complexes are illustrative of the intricate interplay of electrostatics, sterics, and other factors in the formation of preferred configurations. In this project, the structure of the HCl complex of 2-chloro-1,1-difluoroethylene will be investigated using microwave spectroscopy. Ab initio theoretical calculations have revealed several energy minima, the global minimum being a nonplanar complex. Theoretical spectra will be compared with experimental spectra collected via microwave spectrometers to refine rotational constants and thus find an experimental structure.

Dominque Iaccarino: Seminar Title: "Hamburg Cove, CT: Where Sediments Reveal 20th and 21st Century "Legacy" Pollution." Abstract - Hamburg Cove in Connecticut is located near the mouth of the Connecticut River, and has a daily tidal influx that brings in influences from the Long Island Sound. It has high levels of inorganic mercury due to 20th century industrialization and unknown levels of microplastics due to more recent pollution. The toxicity of the mercury in the cove is increased once it is methylated by bacteria, because methylmercury is bioavailable and therefore can bioaccumulate. Past work has shown that at a site closer to the Long Island Sound, the water is brackish and therefore the sediments have more marine influence. It has also been shown that this site has higher levels of mercury methylation. These higher methylation levels were attributed to the higher sulfate levels in the water, but there are many controls on mercury methylation and the quality of organic matter (OM) may also play a significant role. This is because marine OM has been shown to be more labile than terrestrial OM and that mercury methylating bacteria prefer more labile OM. Furthermore, most studies on microplastics have been done in marine ecosytems, but the literature suggests that further research be done in freshwater ecosystems. In this study we will be examining sediment samples from a brackish site and a freshwater site in Hamburg Cove. We will be assessing the quality of OM to see if it has an effect on the mercury methylation levels along with the microplastic content to see if the levels vary by site.