Using the latest advances in structural biology, both predictive bioinformatics tools and experimental methods, we aim to elucidate the structural basis of protein disorder and endeavor to understand the biochemical conditions that further promote their lack of higher order structure and propagation in associated disease states.
Projects include using liposomal-based materials for the capture of environmental pollutants such as polychlorinated biphenyl compounds of which there are 209 distinct congeners. These persistent compounds are heat and photo-resistant and accumulate in the environment where they can alter the local biome and are introduced into the food chain. Liposomal technology has been used for years in biomedical applications, however, we are looking to advance their use in environmental remediation and other potential applications. In studying these materials, we investigate their unique biophysical properties as a function of their composition. Projects are not limited to lipids, but other biomolecular-based materials as well.
Learn more here:
M.D. Rieth. (2022) doi.org/10.1016/j.bbamem.2022.183952
M.D. Rieth and A.J. Lozano. (2020) doi.org/10.1016/j.bbrep.2020.100764
A.J. Lozano and M.D. Rieth. (2019) doi.org/10.1101/829218
Learn more here:
M.D. Rieth. (2022) doi.org/10.1016/j.bbamem.2022.183952
M.D. Rieth and A.J. Lozano. (2020) doi.org/10.1016/j.bbrep.2020.100764
A.J. Lozano and M.D. Rieth. (2019) doi.org/10.1101/829218
Recombinant protein expression is a robust method of producing proteins for downstream analysis and industrial applications. Two common microbes used for high-yield expression are E. coli and Baker’s yeast, Saccharomyces cerevisiae. In spite of the success that has been met using these organisms in expression efforts, challenges remain. Successfully producing sufficient material often necessitates rigorous testing and screening to determine an optimal microbe chassis and expression conditions. Many factors affect intracellular protein expression levels and these projects aim to uncover the role of an intracellular biological process called glycosylation and its interplay with other cell processes. Glycosylation is a type of posttranslational modification whereby sugar residues are added to specific amino acids during protein synthesis in vivo, which can alter levels of protein expression. Aberrant glycosylation commonly occurs during heterologous expression and can lead to misfolding and premature degradation. Understanding the process of glycosylation, the structural signatures that trigger the attachment of sugars and its relation to protein fate during intracellular trafficking is one goal of this project. Together this will help to inform our efforts at protein expression in the future, particularly for “difficult-to-express” proteins, such as membrane proteins.
Learn more here:
R. Karki, S. Rimal, M.D. Rieth. (2021) doi.org/10.1002/yea.3657
Learn more here:
R. Karki, S. Rimal, M.D. Rieth. (2021) doi.org/10.1002/yea.3657
Using lipidomics to characterize the lipid profile of microbes used in industrial processes and those showing promise toward sustainable production of biochemicals and materials is one goal of this work. Currently our efforts are directed at S. cerevisiae to study the effects of metabolic processes on their lipid profile. Specifically, we aim to understand how the production of natural metabolic byproducts such as ethanol, changes the lipid expression profile over time. Previous studies reported in the literature show the biophysical effects of ethanol on cell plasma membrane structural integrity through the disruption of lipid organization. Results from this work will enable the redesign and adaptation of more resilient species using synthetic biology tools for the purpose of sustainable high-yield production of commodity chemicals and compounds for biomedical and biofuel production.