Submission Date

5-7-2020

Document Type

Paper- Restricted to Campus Access

Department

Biochemistry & Molecular Biology

Adviser

Dale Cameron

Committee Member

Samantha Wilner

Committee Member

Ryan Walvoord

Committee Member

Lisa Grossbauer

Department Chair

Anthony Lobo

Department Chair

Eric Williamsen

Project Description

In order to be useful, some of our genetic information needs to be translated into functional proteins. Proteins carry out many important functions within our cells. Once built, proteins must fold in specific and correct ways to function properly. When proteins misfold they can be very detrimental to the organism, since misfolded proteins can lose their intended function or potentially even acquire new, harmful functions. One classification of misfolded proteins is called prions. Prions are able to interact with correctly folded copies of the same type of proteins and transform them into the misfolded prion structure. These misfolded proteins can then clump together to form aggregates that are associated with mammalian neurological diseases like Creutzfeldt–Jakob disease and Kuru in humans, Scrapie in sheep, and Mad Cow disease in cows. However, while in mammals, prions cause diseases, it has been shown that in yeast, prions may provide a fitness advantage in some environments. For example, the [PSI+] prion alters the way in which proteins are synthesized by cells, which can impact the functions and abundance of many different proteins and therefore has the potential to profoundly affect cell physiology. Previous work from our lab has shown that cells with the [PSI+] prion have reduced levels of glucose transporters. Therefore, to begin to investigate possible biological consequences of [PSI+] prion formation, I measured glucose uptake between genetically identical yeast strains that differ only in their prion status (prion free, a weak [PSI+] variant that produces smaller alterations in protein synthesis, or a strong [PSI+] variant that produces larger alterations in protein synthesis). I measured glucose uptake using the fluorescent glucose mimic 2-NBDG for cells grown in low, medium, or high glucose levels. I observed no differences in 2-NBDG uptake between strains grown in different glucose concentrations, but I did find significant differences attributable to prion status. Prions may have beneficial effects during stressful conditions, so we tested various conditions including amino acid starvation, heat stress, and ethanol stress. Differences in glucose uptake can be attributed the type of stress, length of stress, and appear to be yeast strain dependent. Thus, the [PSI+] prion significantly alters glucose uptake in yeast cells, especially following stress. Future studies will examine the extent to which the prion-dependent changes in glucose uptake are due to prion-induced changes in protein synthesis.

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