Associate Professor & Associate Chair for Graduate StudiesOffice: MRB 343Phone: 970-491-0688Education: Ph.D., Mayo Graduate SchoolEmail: Eric.Ross@ColoState.EduResearch Title: Yeast prions as a model for amyloid diseases
Numerous diseases including Parkinson's disease, Alzheimer's disease, late-onset diabetes, and the transmissible spongiform encephalopathies are associated with the formation of ordered protein aggregates, called amyloid fibrils. Despite considerable study, relatively little is known about the forces that drive amyloid aggregation. The major focus of my lab is defining how the amino acid sequence of a protein affects its propensity to form amyloid aggregates.
We are using yeast prions as a model to address this question. A prion is an infectious protein. In yeast, a number of different prions have been identified, each involving the conversion of proteins from a soluble form into an insoluble amyloid form. The rapid growth rate and ease of genetic manipulation of yeast make yeast prions a powerful model system for studying the causes and consequences of amyloid aggregation.
All but one of the yeast prion proteins contains a region that is enriched in the amino acids glutamine and asparagine. Such glutamine/asparagine-rich regions are common in both the yeast and human genome, but predicting whether a given glutamine/asparagine-rich protein will form amyloid aggregates has proven difficult. We recently developed a Prion Aggregation Prediction Algorithm (PAPA) that for the first time allows accurate prediction of the aggregation propensity of glutamine/asparagine-rich proteins (this algorithm can be found at http://combi.cs.colostate.edu/supplements/papa/).
Remarkably, when PAPA is used to scan the human genome, four of the highest scoring proteins are ones that have recently been linked to various degenerative diseases, including ALS and certain forms of dementia. We are currently examining some of the other high-scoring proteins, as well as working to refine the prediction accuracy of PAPA.
Additional interests include using yeast prions to examine the cellular response to amyloid, to identify potential therapeutic targets for the treatment of amyloid diseases and to examine why of all of the amyloid diseases, only a small subset are infectious.
Ross ED, Lee SK, Radebaugh CA, Stargell LA (2012) An integrated biochemistry and genetics outreach program designed for elementary school students, Genetics, 190:305-15.
Maclea KS, Ross ED (2011) Strategies for identifying new prions in yeast, Prion, 5: 263-268.
Toombs JA, Liss NM, Cobble KR, Ben-Musa Z, Ross ED (2011) [PSI] Maintenance Is Dependent on the Composition, Not Primary Sequence, of the Oligopeptide Repeat Domain, PLoS One, 6(7): e21953.
Ross ED, Toombs JA (2010) The effects of amino acid composition on yeast prion formation and prion domain interactions, Prion, 4: 60-65.
Toombs JA, McCarty BR, Ross ED (2010) Compositional determinants of prion formation in yeast, Mol. Cell. Biol., 30: 319-332.
Ross CD, McCarty BR, Hamilton M, Ben-Hur A, Ross ED (2009) A Promiscuous Prion: Efficient Induction of [URE3] Prion Formation by Heterologous Prion Domains, Genetics, 183:929-40.
Shewmaker F, Ross ED, Tycko R, Wickner RB (2008) Amyloids of shuffled prion domains that form prions have a parallel in-register beta-sheet structure, Biochemistry, 47:4000-7.
Watzky MA, Morris AM, Ross ED and Finke RG (2008) Fitting yeast and mammalian prion aggregation kinetic data with the Finke-Watzky 2-step model of nucleation and autocatalytic growth, Biochemistry, 47:10790-10800.
Hansen JC, Lu X, Ross ED, Woody RW (2006) Intrinsic protein disorder, amino acid composition, and histone terminal domains. J Biol Chem. 281: 1853-1856.
Ross ED, Edskes HK, Terry MJ, Wickner RB (2005) Primary sequence independence for prion formation. Proc Natl Acad Sci USA. 102: 12825-12830.
Ross ED, Minton A, Wickner RB (2005) Prion domains: sequences, structures and interactions. Nat Cell Biol. 7: 1039-1044.