Submission Date

7-19-2019

Document Type

Paper- Restricted to Campus Access

Department

Biochemistry & Molecular Biology

Second Department

Biology

Faculty Mentor

Dale Cameron

Comments

Presented during the 21st Annual Summer Fellows Symposium, July 19, 2019 at Ursinus College.

This project was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R15GM119081.

Project Description

In order to be useful, 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 of glucose following an initial growth period with or without amino acid starvation. Following growth in the amino acid starved condition, 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. The glucose intake was greatly increased in the “starved” condition compared to amino acids. These differences also seem to be strain dependent. Thus, the [PSI+] prion significantly alters glucose uptake in yeast cells, especially following amino acid starvation. 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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