Research projects in my laboratory cover a wide range of systems broadly classified as biomedical natural products, food and dairy, and computational chemistry. My group explores the interface between chemistry and biology to understand the mechanism of action for bioactive components isolated from natural products. Projects in my laboratory are instrumentation and computationally intensive with an emphasis on nuclear magnetic resonance spectroscopy, high pressure liquid chromatography, mass spectrometry, infrared spectroscopy, circular dichroism, cell culture, molecular docking, and molecular dynamics simulations.
The main research topics that students in my lab investigate include: (1) computational prediction of conotoxin peptides for Parkinson’s disease therapies; (2) steroidal alkaloids from Veratrum californicum for cancer treatments; (3) computational and NMR studies to identify novel cures for heart disease, and (4) potatoes, onions, milk, and cheese. My lab also works closely with area industry to address issues in food processing, nutraceuticals, ethanol distillation, candle fragrances, and a variety of other topics.
A goal of my research is to ensure the projects that I propose can be accomplished by undergraduate and graduate students, are worthy of publication, and have the potential to be presented at local, regional, and national conferences. It is important for students to be exposed to cutting edge advances in science and for them to experience relevant, real-world examples of how their work fits into the evolving interdisciplinary and collaborative realm of research. Each of my projects is evaluated for level of difficulty and potential for access to external funding. Primary long term projects are listed below with many additional projects coming available on a rotating basis.
Please email me to discuss research opportunities that may fit your interests at firstname.lastname@example.org. Lab personnel include Biomolecular Sciences Ph.D. candidates, Chemistry Masters students, and undergraduate chemistry majors.
Research Project Overview
Project 1) Computational prediction of conotoxin peptides for Parkinson’s disease therapies
Conotoxins are small cysteine rich peptides that have proven application as molecular probes and therapeutics for epilepsy, chronic pain, and Parkinson’s disease. We investigate alpha-conotoxins that target dopaminergic receptors in the mammalian brain. Our work uses a combination of computational prediction and wet bench validation of binding paradigms to create improved binding affinity and selectivity for conotoxin inspired small molecule drugs to target nicotinic acetylcholine receptors. Students working on this project can gain experience with homology modeling, molecular docking, high throughput virtual screening, peptide synthesis, biomolecular NMR, molecular dynamics simulations, and PC-12 cell bioactivity assessment. Shown below are students working with the peptides synthesizer and 600 MHz Bruker Avance III NMR spectrometer to go from peptide structure to small molecule drug for Parkinson’s disease treatment.
- Turner, M., et al., 2009 Bioorg. Med. Chem. 17, 5894-5899.
- McDougal, O.M., et al., 2013 J. Phys. Chem. B 117, 2653-2661.
- Sambasivarao, S.V., et al., 2014 ChemBioChem 15, 413-424.
- King, M., et al., 2016 J. Chem. Inf. Model. 56, 2378-2387.
- King, M., et al., 2018 BMC Bioinformatics 19, DOI: https://doi.org/10.1186/s12859-018-2153-y.
Project 2) Steroidal alkaloids from Veratrum californicum for cancer treatments
Students interested in natural products chemistry should consider the extraction, isolation, and characterization of medicinal alkaloids from Veratrum californicum, a plant indigenous to Idaho. Among the alkaloids produced by the Idaho Corn Lily is cyclopamine. Cyclopamine functions to inhibit the Hedgehog pathway, a dormant developmental channel that becomes active in many types of cancer including breast, pancreatic, and basal cell carcinoma to name a few. We use a combination of modern scientific methods to identify and quantitate components of the plant biomass including high pressure liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. To assess the bioactivity of novel alkaloids isolated from the plant material, we use Shh Light II cells. The pictures below show the progression from plant to HPLC separation to bioactivity evaluation.
To learn more about this project, refer to select literature published by students in the lab:
- Chandler, C.M., et al., 2013 Nat. Prod. Comm. 8, 1059-1064.
- Chandler, C.M. and McDougal, O.M. 2014 Phytochem. Rev. 13, 671-694.
- Turner, M.W., et al., 2016 Bioorg. Med. Chem. 24, 3752-3757.
- Anwar, M., et al., 2018 Clin. Toxicol. DOI: https://doi.org/10.1080/15563650.2018.1442007.
Project 3) Computational and NMR studies to identify novel cures for heart disease
The most common treatment for heart disease is statin drugs like Lipotor, an HMG CoA reductase inhibitor used to lower cholesterol levels in the blood. The problem with this drug therapy is that nearly half of all heart attack patients that end up in emergency rooms do not have elevated levels of cholesterol. Thus, our collaborator, Dr. Ken Fujise at the University of Texas Medical Branch in Galveston, has identified a novel target for heart disease treatment, the protein fortilin. Fortilin prevents programed cell death, which is the immune systems natural mechanism to break down macrophages that accumulate cholesterol, a condition that leads to atherosclerosis. When fortilin is abundant, macrophages increase in size as they accumulate cholesterol, and turn into foam cells, which cause atherosclerosis, and eventual heart attack or stroke. In collaboration with Drs. Matt King and Lisa Warner, we computationally predict ligand binding paradigms for fortilin inhibitors and then validate the prediction using NMR spectroscopy. This project is currently funded by an NIH R01 grant through 2021. The pictures below show the progression from scientific team to computational prediction and ultimately NMR experimentation.
To learn more about this project, refer to select literature published by this team of scientists:
- Chattopadhyay, A., et al., 2016 Scientific Rep. DOI: https://www.nature.com/articles/srep18701.
- Pinkaew, D., et al., 2017 Nature Comm. 8, DOI: https://www.nature.com/articles/s41467-017-00029-1.
Project 4) Potatoes, onions, milk, and cheese
My group began exploring nutraceuticals and food chemistry following my 2014 sabbatical experience in the Food and Crop research laboratory of Dr. Nigel Perry at the University of Otago, Dunedin, NZ. In Dr. Perry’s lab I investigated alkaloid and phenolic constituents from New Zealand Sophora spp. My work led to two publications and set the stage for our current projects involving the measurement of oxidative degradation products in oil formed during the processing of French fries by NIR spectroscopy, the use of GC-MS to track the degradation of toxic organosulfides in onions during steam distillation, the degree of protein denaturation in milk proteins that occurs during processing by FT-IR, and inhibitors of propionibacteria that devalue milk for use in the production of Swiss cheese. Every one of the food projects has been well funded by private industry, Idaho State Department of Agriculture, or the BUILD Dairy program.
To learn more about these projects, refer to select literature published by this team of scientists:
- McDougal, O.M., et al. 2015 Phytochem. 118, 9-16.
- French, J.M.T., et al. 2016 Nat. Prod. Comm. 11, 607-609.
- Kondamudi, N., et al. 2016 Nat. Prod. Comm. 11, 1215-1216.
- Kondamudi, N., et al. 2017 Amer. J. Potato Res. 94, 153-158.
- McDougal, O.M., et al. 2018 NZJ Botany, DOI: https://doi.org/10.1080/0028825X.2018.1472107.