Eric Ross

Eric RossProfessor
Office: MRB 343
Phone: 970-491-0688
Education: Ph.D., Mayo Graduate School
Email: Eric.Ross@ColoState.Edu
Research Title: Yeast prions as a model to study protein aggregation

Our research focuses on the causes and consequences of functional and pathogenic protein aggregation. To address these questions, we utilize yeast genetics, in vitro biochemistry, and bioinformatics. Numerous diseases including Parkinson's disease, Alzheimer's disease, 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. We are working to understand 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 are infectious protein that generally result from the conversion of proteins from a soluble form into an insoluble amyloid form.  We have used the yeast prions to developed prediction methods to identify potential new prion proteins, and to predict the effects of mutations on prion-like amyloid aggregation. Additionally, while protein aggregation is frequently pathogenic, regulated protein aggregation is used to control a variety of cellular processes. Stress granules provide a fascinating example of these functional protein assemblies. Stress granules are ribonuceloprotein assemblies that form in response to stress. Many of the proteins within stress granules contain prion-like domains (PrLDs), which are protein domains that resemble yeast prion domains. Mutations in a number of these PrLD-containing proteins lead to degenerative diseases, including amyotrophic lateral sclerosis (ALS). Emerging evidence suggests that these PrLDs are evolved to form dynamic, reversible liquid-like interactions that promote protein recruitment to stress granules. Disease-associated mutations are thought to perturb the dynamics and regulation of these assemblies. We are working to understand the regulation of these protein assemblies, and to define how the sequence of PrLDs affects the formation and reversibility of these assemblies.

Selected Publications

Cascarina SM, Ross ED (2018) Proteome-scale relationships between local amino acid composition and protein fates and functions, PLoS Comput Biol. 14:e1006256. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006256

Cascarina SM, Paul KR, Machihara S, Ross ED (2018) Sequence features governing aggregation or degradation of prion-like proteins, PLoS Genet. 14:e1007517. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007517

Bakthavachalu B, Huelsmeier J, Sudhakaran IP, Hillebrand J, Singh A, Petrauskas A, Thiagarajan D, Sankaranarayanan M, Mizoue L, Anderson EN, Pandey UB, Ross E, VijayRaghavan K, Parker R, Ramaswami M (2018) RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration. Neuron, 98:754-766.e4.

Paul KR, Molliex A, Cascarina S, Boncella AE, Taylor JP, Ross ED (2017) Effects of Mutations on the Aggregation Propensity of the Human Prion-Like Protein hnRNPA2B1. Mol Cell Biol., 37:e00652-16.

Afsar Minhas FUA, Ross ED, Ben-Hur A (2017) Amino acid composition predicts prion activity, PLoS Comput. Biol., 13(4):e1005465. http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005465

Li S, Zhang P, Freibaum BD, Kim NC, Kolaitis RM, Molliex A, Kanagaraj AP, Yabe I, Tanino M, Tanaka S, Sasaki H, Ross ED, Taylor JP, Kim HJ (2016) Genetic interaction of hnRNPA2B1 and DNAJB6 in a Drosophila model of multisystem proteinopathy, Hum. Mol. Gen., 25:936-950.

Paul KR, Ross ED (2015) Controlling the prion propensity of glutamine/asparagine-rich proteins, Prion, 9:347-354.

Paul KR, Hendrich CG, Waechter A, Harman MR, Ross ED (2015) Generating new prions by targeted mutation or segment duplication, Proc. Natl. Acad. Sci. USA, 112: 8584-8589.  http://www.pnas.org/content/112/28/8584.long

MacLea KS, Paul KR, Ben-Musa Z, Waechter A, Shattuck JE, Gruca M, Ross ED (2015) Distinct Amino Acid Compositional Requirements for Formation and Maintenance of the [PSI+] Prion in Yeast, Mol Cell Biol, 35: 885-911.

Cascarina SM, Ross ED, Yeast prions and human prion-like proteins: sequence features and prediction methods (2014) Cell Mol Life Sci, 71:2047-63.

Gonzalez Nelson AC, Paul KR, Petri M, Flores N, Rogge RA, Cascarina SM, Ross ED (2014) Increasing prion propensity by hydrophobic insertion, PLoS One, 9:e89286.

Ross ED, MacLea KS, Anderson C, Ben-Hur A (2013) A bioinformatics method for identifying Q/N-rich prion-like domains in proteins, Methods Mol Biol, 1017: 219-28.

HJ Kim et al., Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS (2013) Nature, 495: 467-673.

Toombs JA, Petri M, Paul KR, Kan GY, Ben-Hur A, Ross ED (2012) De novo design of synthetic prion domains, Proc Natl Acad Sci USA, 109: 6519-6524.

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.

NIH PubMed Publications List