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Susan W. Liebman

Research Professor
Biochemistry and Molecular Biology
University of Nevada/Mail Stop 330
1664 North Virginia Street
Reno,  Nevada   89557

 

Office: (775) 682-7338
Lab: 327-2251

Fax: 784-1419

Email: sliebman@unr.edu
Building: Howard Medical Science,  Office 151

 

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EDUCATION

Erasmus Hall H.S., Brooklyn, NY
B.A. 1968 Massachusetts Institute of Technology, Cambridge, MA
M.S. 1969 Harvard University, Cambridge, MA
Ph.D. 1974 University of Rochester, Rochester, NY

 

ACADEMIC & RESEARCH INTEREST

Protein as the hereditary material - a yeast model for prion diseases in mammals

Certain neurodegenerative diseases, such as ‘mad cow’ disease, are transmitted in an unusual way-- so unusual that it challenges the central dogma. Indeed, the infectious agent for these diseases appears to be the PrP protein without any nucleic acid. Infectivity depends upon the shape into which the PrP protein is folded: when some PrP is in its disease-causing (‘prion’) conformation, it converts normal PrP into that form too. Several genetic traits in yeast are propagated by this unusual ‘protein only’ mechanism, and although they involve proteins distinct from PrP, the term prion has been expanded to include them. We are using yeast to elucidate the factors that influence prion inheritance and to look for new prions.

One yeast prion, [PSI+], is caused by an altered shape of a protein called eRF3 (a translational release factor). When eRF3 is in the prion shape it aggregates and loses its normal activity and this causes the [PSI+] phenotype. An important piece of evidence for this prion hypothesis was our finding that a transient excess of eRF3 protein induces the permanent appearance of [PSI+]. Presumably this occurs because the excess eRF3 increases the chance that some eRF3 molecules will accidentally fold into the prion shape. Our finding that an intermediate level of the Hsp104 chaperone is required for the propagation of [PSI+] also provides dramatic support for the prion hypothesis since the only function of Hsp104 is to facilitate protein folding. This finding has spawned considerable interest in the role of other chaperones in the maintenance of various prions.

We have identified nine prion candidate genes from a genetic screen and are now characterizing these putative prion proteins. We are also examining the interactions between prions and find that different prions influence the appearance and propagation of other prions.

Can prion proteins with the identical amino acid sequence take on more then one heritable prion shape? It appears that PrP can! These different prions have been called ‘strains’. The relationship between different prion strains and their effects on prion infectivity are of great interest. This can now be studied in yeast because we found [PSI+] ‘strains’ and [PIN+] ‘strains’ with distinct heritable phenotypes. We are currently examining the biochemical differences and genetic interactions between these prion ‘strains’.

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REPRESENTATIVE PUBLICATIONS

 

Journals
Mathur V, Taneja V, Sun Y, Liebman SW 2010, Analyzing the birth and propagation of two distinct prions, [PSI+] and [Het-s]y, in yeast, Mol Biol Cell. 21:1449-61  
Manogaran AL, Fajardo VM, Reid RJ, Rothstein R, Liebman SW 2010, Most, but not all, yeast strains in the deletion library contain the [PIN+] prion, Yeast. 27:159-66  
Vishveshwara N and Liebman SW 2009, Heterologous cross-seeding mimics cross-species prion conversion in a yeast model, BMC Biol 7:26  
Patel BK, Gavin-Smyth J and Liebman SW 2009, The yeast global transcriptional co-repressor Cyc8 can propagate as a prion., Nat Cell Biol 11: 344-349  
Bagriantsev SN, Gracheva EO, Richmond JE and Liebman SW 2008, Variant-specific [PSI+] infection is transmitted by Sup35 polymers within [PSI+] aggregates with heterogeneous protein composition, Mol Biol Cell 19: 2433-2443  
Taneja V, ML Maddelein, N Talarek, SJ Saupe and SW Liebman 2007, A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast, Mol Cell 27:67-77  
Bagriantsev S and Liebman S 2006, Modulation of Abeta42 low-n oligomerization using a novel yeast reproter system, BMC Biol 4: 32  
Derkatch IL, SM Uptain, TF Outeiro, R Krishnan, SL Lindquist and SW Liebman 2004, Effects of Q/N-rich, polyQ, and non-polyQ amyloids on the de novo formation of the [PSI+] prion in yeast and aggregation of Sup35 in vitro., Proc Natl Acad Sci USA 101: 12934-39  
Derkatch, IL, ME Bradley, JY Hong and SW Liebman 2001, Prions affect the appearance of other prions: the story of [PIN+]., Cell 106:171-82