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  Estimating the rate of prion aggregate amplification in yeast with a generation and structured population model

Banks, H. T., Flores, K. B., Langlois, C. R., Serio, T. R., & Sindi, S. S. (2018). Estimating the rate of prion aggregate amplification in yeast with a generation and structured population model. Inverse Problems in Science and Engineering, 26(2), 257-279. doi:10.1080/17415977.2017.1316498.

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 Creators:
Banks, H. T.1, Author
Flores, Kevin B.1, Author
Langlois, Christine R.2, Author              
Serio, Tricia R.1, Author
Sindi, Suzanne S.1, Author
Affiliations:
1external, ou_persistent22              
2Wollert, Thomas / Molecular Membrane and Organelle Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565175              

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Free keywords: PSI+ PRION; PROBABILITY-DISTRIBUTIONS; SACCHAROMYCES-CEREVISIAE; GUANIDINE-HYDROCHLORIDE; PARAMETER-ESTIMATION; DYNAMICS; SIZE; DIVISION; PROLIFERATION; TRANSMISSIONEngineering; Mathematics; Structured population model; aggregate data; inverse problem; PDEs; prion; General biology and biomathematics;
 Abstract: Prions are a special class of proteins capable of adopting multiple (misfolded) conformations, some of which have been associated with fatal diseases in mammals such as bovine spongiform encephalopathy or Creutzfeldt-Jakob Disease. Prion diseases, like protein misfolding diseases in general, are caused by the formation and amplification of ordered aggregates of proteins called amyloids. While such diseases in mammals can take decades to form, yeast have a variety of prion phenotypes that occur over a few hours, making this system an ideal model for protein misfolding disease in general. Most experimental assays of colonies with yeast prions provide steady-state population observations which complicate the inference of biochemical parameters both by the inability to directly measure aggregate amplification and by obscuring heterogeneity between cells. We develop a mathematical and inverse problem formulation to determine the amplification rate with prion aggregates from single-cell measurements observed in propagon amplification experiments. We demonstrate the ability of our formulation to determine heterogeneous amplification rates on simulated and experimental data. Our results show that aggregate amplification rates for two prion variants are strongly bimodal, suggesting that the generational structure in the yeast population impacts the ability of prion aggregates to amplify.

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Language(s): eng - English
 Dates: 2017-04-182018
 Publication Status: Published in print
 Pages: 23
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Inverse Problems in Science and Engineering
Source Genre: Journal
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Publ. Info: 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND : TAYLOR & FRANCIS LTD
Pages: - Volume / Issue: 26 (2) Sequence Number: - Start / End Page: 257 - 279 Identifier: ISSN: 1741-5977