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Professor Mick Tuite

Professor of Molecular Biology/Fellow of the American Academy of Microbiology

School of Biosciences


Professor Mick Tuite joined the School of Biosciences in 1983 after conducting postdoctoral research at the University of California (1978-81) and the University of Oxford (1981-83). He began his research studies on yeast whilst a PhD student under the supervision of Dr Brian Cox at the 'Botany School' in Oxford. His research interests have largely focused on the mechanism and control of translation in yeast but more recently his interests have moved to yeast prion proteins and molecular chaperones. The research in his group has been extensively funded by grants from the BBSRC, Wellcome Trust and the Leverhulme Trust.

Mick is a member of the Kent Fungal Group and deputy Chair of the Scientific Conferences Committee of the Microbiology Society.

ORCID ID: 0000-0002-5214-540X

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Also view these in the Kent Academic Repository

Ness, F. et al. (2017). Over-expression of the molecular chaperone Hsp104 in Saccharomyces cerevisiae results in the malpartition of [PSI + ] propagons. Molecular Microbiology [Online] 104:125-143. Available at:
Marchante, R. et al. (2017). The physical dimensions of amyloid aggregates control their infective potential as prion particles. eLife [Online] 6:e27109. Available at:
von der Haar, T. et al. (2017). The control of translational accuracy is a determinant of healthy ageing in yeast. Open Biology [Online] 7:160291. Available at:
Cox, B. and Tuite, M. (2017). The life of [PSI]. Current Genetics [Online]. Available at:
Sideri, T. et al. (2017). The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe. Microbial Cell [Online] 4:16-28. Available at:
True, H. et al. (2017). Disrupting the cortical actin cytoskeleton points to two distinct mechanisms of yeast [PSI+] prion formation. PLOS Genetics [Online] 13:e1006708. Available at:
Adam, I., Jossé, L. and Tuite, M. (2017). Human TorsinA can function in the yeast cytosol as a molecular chaperone. Biochemical Journal [Online] 474:3439-3454. Available at:
Tuite, M. (2016). Remembering the Past: A New Form of Protein-Based Inheritance. Cell [Online] 167:302-303. Available at:
Bastow, E. et al. (2016). New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis. Journal of cell science [Online] 129:4118-4129. Available at:
Tuite, M. (2015). Yeast prions: Paramutation at the protein level? Seminars in Cell & Developmental Biology [Online] 44:51-61. Available at:
Tuite, M., Staniforth, G. and Cox, B. (2015). [PSI+] turns 50. Prion [Online] 9:318-332. Available at:
Doronina, V. et al. (2015). Oxidative stress conditions increase the frequency ofde novoformation of the yeast [PSI+] prion. Molecular Microbiology [Online] 96:163-174. Available at:
Mead, E. et al. (2014). Control and regulation of mRNA translation. Biochemical Society Transactions [Online] 42:151-154. Available at:
Chu, D. et al. (2014). Translation elongation can control translation initiation on eukaryotic mRNAs. EMBO Journal [Online] 33:21-34. Available at:
Tuite, M., Howard, M. and Xue, W. (2014). Dynamic Prions Revealed by Magic. Chemistry & Biology [Online] 21:172-173. Available at:
Staniforth, G. and Tuite, M. (2014). Monoculture Breeds Poor Social Skills. Cell [Online] 158:975-977. Available at:
Preiss, T. et al. (2013). Specialized Yeast Ribosomes: A Customized Tool for Selective mRNA Translation. PLoS ONE [Online] 8:e67609. Available at:
Marchante, R. et al. (2013). Structural Definition Is Important for the Propagation of the Yeast [PSI+] Prion. Molecular Cell [Online] 50:675-685. Available at:
Jossé, L. et al. (2012). Probing the role of structural features of mouse PrP in yeast by expression as Sup35-PrP fusions. Prion [Online] 6:201-210. Available at:
Tuite, M., Marchante, R. and Kushnirov, V. (2011). Fungal Prions: Structure, Function and Propagation. Topics in Current Chemistry [Online] 305:257-298. Available at:
Afanasieva, E. et al. (2011). Molecular Basis for Transmission Barrier and Interference between Closely Related Prion Proteins in Yeast. Journal of Biological Chemistry [Online] 286:15773-15780. Available at:
Sideri, T. et al. (2011). Methionine Oxidation of Sup35 Protein Induces Formation of the [PSI+] Prion in a Yeast Peroxiredoxin Mutant. Journal of Biological Chemistry [Online] 286:38924-38931. Available at:
Jossé, L., Smales, C. and Tuite, M. (2010). Transient expression of human TorsinA enhances secretion of two functionally distinct proteins in cultured Chinese hamster ovary (CHO) cells. Biotechnology and Bioengineering [Online] 105:556-566. Available at:
Sideri, T. et al. (2010). Ribosome-associated peroxiredoxins suppress oxidative stress-induced de novo formation of the [PSI+] prion in yeast. Proceedings of the National Academy of Sciences [Online] 107:6394-6399. Available at:
Tuite, M. and Serio, T. (2010). The prion hypothesis: from biological anomaly to basic regulatory mechanism. Nature Reviews Molecular Cell Biology [Online] 11:823-833. Available at:
Moosavi, B., Wongwigkarn, J. and Tuite, M. (2010). Hsp70/Hsp90 co-chaperones are required for efficient Hsp104-mediated elimination of the yeast [PSI+] prion but not for prion propagation. Yeast [Online] 27:167-179. Available at:
Merritt, G. et al. (2010). Decoding accuracy in eRF1 mutants and its correlation with pleiotropic quantitative traits in yeast. Nucleic acids research [Online] 38:5479-5492. Available at:
Byrne, L. et al. (2009). The Number and Transmission of [PSI+] Prion Seeds (Propagons) in the Yeast Saccharomyces Cerevisiae. PLoS ONE [Online] Online. Available at:
Tuite, M. et al. (2008). Cellular factors important for the de novo formation of yeast prions. Biochemical Society Transactions [Online] 36:1083-1087. Available at:
Studte, P. et al. (2008). tRNA and protein methylase complexes mediate zymocin toxicity in yeast. Molecular Microbiology [Online] 69:1266-1277. Available at:
Byrne, L. et al. (2007). Cell division is essential for elimination of the yeast [PSI+] prion by guanidine hydrochloride. Proceedings of the National Academy of Sciences of the United States of America [Online] 104:11688-11693. Available at:
von der Haar, T. et al. (2007). Development of a novel yeast cell-based system for studying the aggregation of Alzheimer's disease-associated A beta peptides in vivo. Neurodegenerative Diseases [Online] 4:136-147. Available at:
Cole, D. et al. (2007). Approximations for expected generation number. Biometrics [Online] 63:1023-1030. Available at:
von der Haar, T. and Tuite, M. (2007). Regulated translational bypass of stop codons in yeast. Trends in Microbiology [Online] 15:78-86. Available at:
Ridout, M. et al. (2006). New approximations to the Malthusian parameter. Biometrics [Online] 62:1216-1223. Available at:
Shkundina, I. et al. (2006). The role of the N-terminal oligopeptide repeats of the yeast Sup35 prion protein in propagation and transmission of prion variants. Genetics [Online] 172:827-835. Available at:
Zenthon, J. et al. (2006). The [PSI+] prion of Saccharomyces cerevisiae can be propagated by an Hsp104 orthologue from Candida albicans. Eukaryotic Cell [Online] 5:217-225. Available at:
Alderton, A. et al. (2006). Zeocin resistance as a dominant selective marker for transformation and targeted gene deletions in Candida glabrata. Mycoses [Online] 49:445-451. Available at:
Tuite, M. and Cox, B. (2006). The [PSI+] prion of yeast: a problem of inheritance. Methods [Online] 39:9-22. Available at:
Klengel, T. et al. (2005). Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Current Biology [Online] 15:2177-2177. Available at:
Klengel, T. et al. (2005). Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Current Biology [Online] 15:2021-2026. Available at:
Lund, P. and Tuite, M. (2005). Preventing illicit liaisons in Poland. EMBO Reports [Online] 6:1126-1130. Available at:
Byrne, L., O'Callaghan, K. and Tuite, M. (2005). Heterologous gene expression in yeast. Methods in Molecular Biology [Online] 308:51-64. Available at:
O'Callaghan, K., Byrne, L. and Tuite, M. (2005). Extraction and denaturing gel electrophoretic methodology for the analysis of yeast proteins. Methods in Molecular Biology [Online] 308:357-373. Available at:
Jones, G. and Tuite, M. (2005). Chaperoning prions: the cellular machinery for propagating an infectious protein? Bioessays [Online] 27:823-832. Available at:
Cole, D. et al. (2004). Estimating the number of prions in yeast cells. Mathematical Medicine and Biology [Online] 21:369-395. Available at:
Osherovich, L. et al. (2004). Dissection and design of yeast prions. PLoS Biology [Online] 2:442-451. Available at:
Tuite, M. (2004). Cell biology: the strain of being a prion. Nature [Online] 428:265-267. Available at:
Santos, M. et al. (2004). Driving change: the evolution of alternative genetic codes. Trends in Genetics [Online] 20:95-102. Available at:
Tuite, M. and Koloteva-Levine, N. (2004). Propagating prions in fungi and mammals. Molecular Cell [Online] 14:541-552. Available at:
Tuite, M. and Cox, B. (2003). Propagation of yeast prions. Nature Reviews Molecular Cell Biology [Online] 4:878-889. Available at:
Massey, S. et al. (2003). Comparative evolutionary genomics unveils the molecular mechanism of reassignment of the CTG codon in Candida spp. Genome Research [Online] 13:544-557. Available at:
Cox, B., Ness, F. and Tuite, M. (2003). Analysis of the generation and segregation of propagons: entities that propagate the [PSI+] prion in yeast. Genetics [Online] 165:23-33. Available at:
Resende, C. et al. (2003). Prion protein gene polymorphisms in Saccharomyces cerevisiae. Molecular Microbiology [Online] 49:1005-1018. Available at:
Moura, G. et al. (2002). Stop codon decoding in Candida albicans: from non-standard back to standard. Yeast [Online] 19:727-733. Available at:
Fernandez-Bellot, E. et al. (2002). The [URE3] phenotype: evidence for a soluble prion in yeast. EMBO Reports [Online] 3:76-81. Available at:
Ness, F. et al. (2002). Guanidine hydrochloride inhibits the generation of prion "seeds" but not prion protein aggregation in yeast. Molecular and Cellular Biology [Online] 22:5593-5605. Available at:
Resende, C. et al. (2002). The Candida albicans Sup35p protein (CaSup35p): function, prion-like behaviour and an associated polyglutamine length polymorphism. Microbiology 148:1049-1060.
Ferreira, P. et al. (2001). The Elimination of the Yeast [PSI+] Prion by Guanidine Hydrochloride is the result of Hsp104 Inactivation. Molecular Microbiology [Online] 40:1357-1369. Available at:
O'Sullivan, J. et al. (2001). The Candida Albicans Gene Encoding the Cytoplasmic Leucyl-tRNA Synthetase: Implications for the Evolution of CUG Codon Reassignment. Gene [Online] 275:133-140. Available at:
O'Sullivan, J., Davenport, J. and Tuite, M. (2001). Codon Reassignment and the Evolving Genetic Code: Problems and Pitfalls in Post-genome Analysis. Trends in Genetics [Online] 17:20-22. Available at: http://dx.doi./10.1016/S0168-9525(00)02144-2.
O'Sullivan, J. et al. (2001). Seryl-tRNA Synthetase is not responsible for the Evolution of CUG Codon Reassignment in Candida Albicans. Yeast [Online] 18:313-322. Available at:<313::AID-YEA673>3.0.CO;2-7.
Parham, S., Resende, C. and Tuite, M. (2001). Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions. EMBO Journal [Online] 20:2111-2119. Available at:
Tuite, M. (2000). Cell biology. Sowing the protein seeds of prion propagation. Science [Online] 289:556-557. Available at:
Eaglestone, S. et al. (2000). Guanidine hydrochloride blocks a critical step in the propagation of the prion-like determinant [PSI+] of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America [Online] 97:240-244. Available at:
Song, H. et al. (2000). The crystal structure of human eukaryotic release factor eRF1 - Mechanism of stop codon recognition and peptidyl-tRNA hydrolysis. Cell [Online] 100:311-321. Available at:
Book section
Tuite, M. and von der Haar, T. (2016). Transfer RNA in Decoding and the Wobble Hypothesis. in: eLS. Wiley, pp. 1-7. Available at:
Tuite, M. (2013). The Natural History of Yeast Prions. in: Sariaslani, S. and Gadd, G. M. eds. Advances in Applied Microbiology. Elsevier Inc., pp. 85-137. Available at:
Jossé, L., Smales, C. and Tuite, M. (2012). Engineering the Chaperone Network of CHO Cells for Optimal Recombinant Protein Production and Authenticity. in: Recombinant Gene Expression. Springer New York, pp. 595-608. Available at:
Cox, B., Byrne, L. and Tuite, M. (2007). Prion stability. in: Chernoff, Y. O. ed. Protein-based inheritance. Landes Biosciences, pp. 56-72.
Tuite, M. et al. (2007). Yeast prions and their analysis in vivo. in: Yeast gene analysis, second edition. San Diego, US: Elsevier Academic Press, pp. 491-526.
Tuite, M. and Cox, B. (2007). The genetic control of the formation and propagation of the [PSI+] prion. in: Chernoff, Y. O. ed. Protein-based inheritance. Landes Biosciences, pp. 14-29.
Conference or workshop item
Whalley, J., Tuite, M. and Johnson, C. (2002). A virtual lab for exploring the [PSI]+ yeast prion. in: Valafar, F. ed. Proceedings of the International Conference on Mathematics and Engineering Techniques in Medicine and Biological Sciences. USA: CSERA Press, pp. 583-589. Available at:
Tuite, M. (2016). Molecular communication: An acid tale of prion formation. eLife [Online] 5. Available at:
Tuite, M. and Cox, B. (2007). The genetic control of the formation and propagation of the [PSI+] prion. Prion 1:101-109.
Tuite, M. and Melki, R. (2007). Protein misfolding and aggregation in ageing and disease: molecular processes and therapeutic perspectives. Prion 1:116-120.
Tuite, M. (2000). Yeast prions and their prion-forming domain. Cell [Online] 100:289-292. Available at:
Showing 77 of 148 total publications in KAR. [See all in KAR]


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Protein folding, misfolding and disease

Most proteins must take up a specific three-dimensional shape in order to carry out their assigned biological function(s). How cells ensure proteins take up their desired shape involves a complex interplay between a wide range of proteins (e.g. chaperones) and various post-translational modifications (e.g. disulphide bonds) that mould the protein chain into shape and then ensure that the desired shape is maintained. Failure to do so at best results in their destruction by the cell’s protein quality control machinery, at worst causing cellular malfunction and disease.
The Tuite laboratory are using the yeast Saccharomyces cerevisiae to explore not only the mechanisms used to achieve correct protein folding in the eukaryotic cell, but also exploring reasons why proteins can misfold and uncovering what impact such misfolded proteins can have on the host cell.


The yeast Saccharomyces cerevisiae in its many guises

Recent reviews published by the Tuite Laboratory

  • Tuite, M.F. and Serio, T.R. (2010). The prion hypothesis: from biological anomaly to basic regulatory mechanism. Nature Reviews in Molecular Cell Biology 11: 823-833.
  • Tuite, M.F. (2013) The natural history of yeast prions. Advances in Applied Microbiology 84: 85-137.
  • Tuite, M.F. (2015) Yeast prions: paramutation at the protein level? Seminars in Cell and Developmental Biology 44: 51-61.
  • Staniforth, G.L. and Tuite, M.F. (2014) Monoculture breeds poor social skills. Cell 158: 975-977
  • Tuite, M.F. (2016) Remembering the past: a new form of protein-based inheritance. Cell 167: 302-303.

....and on-line seminar

  • Tuite, M.F.. (2008), "Mechanisms of yeast prion propagation", in Wickner, R. (ed.), Prions and Amyloids: Self-propagating protein structures in mammals, yeast and fungi, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at

Current projects


Part of the protein secretion processes in eukaryotic cells is to ensure that secreted proteins adopt a structure in which they have optimal activity. The folded structure of a protein chain depends on interactions between individual amino acids. A specific type of interaction that is critical to the activity of many secreted proteins occurs when two cysteine residues form bonds between the sulphur atoms they contain i.e. the disulphide bond.

Disulphide bond formation occurs as an integral part of the secretion process, and involves a cascade of specific enzymes. These enzymes remove an electron from the interacting cysteines, allowing them to form a bond between them that determines the affected protein's shape. The electron is then passed between different enzymes and ultimately onto an oxygen atom, which reacts with water to form hydrogen peroxide. Since the latter is toxic if present in large amounts, it has to be removed in a further series of reactions. The entirety of these reactions is called the oxidative protein folding (OPF) pathway and is the focus of this project.  




The oxidative protein folding pathway in eukaryotic cells (left) and visualisation of the yeast ER using a Sec63-GFP fusion

There are fundamental differences between the OPFs of different types of eukaryotic cells. We are exploring the differences between the OPFs of two specific cell types (simple yeast cells and complex human cells) to improve our understanding of the molecular machinery involved in oxidative folding. Such knowledge will also improve our ability to manipulate the pathway by rational genetic engineering in order to generate better producing cells for the bioprocessing industry. Human cells have a much more complex OPF, with different forms of the OPF enzymes that are only act on specific types of target proteins. Interestingly, human cells are also able to use the toxic hydrogen peroxide to drive the OPF reactions, whereas yeast cannot do this.

In our project we are using a four-pronged strategy to exploit these differences:
[1] Analysing the enzymes of the OPF machinery from yeast and human cells using in vitro and in vivo approaches;
[2] Using the information from these experiments to generate a computational model that can predict properties of the OPF pathways in vivo;
[3] Using the predictions made with the computational model to change properties of the yeast OPF enzymes; and
[4] Humanising the yeast ER by introduction of components of the human OPF pathway.

Overall, this strategy is enabling us to gain a better understanding of how the OPF machinery functions, and in the longer term will enable us to engineer yeast cells that are better suited for use in bioprocessing applications.

The ‘PDI Team’: Gemma Staniforth, Mick Tuite, Dave Beal, Robert Freedman, Emma Bastow

Researchers: Dr Dave Beal (postdoc), Dr Emma Bastow (postdoc)

Collaborators:Professor Robert Freedman (University of Warwick)

Funded by: BBSRC

Modelling prion dynamics in the living yeast cell


Two models have been used to explain the self-propagation of prions in yeast and mammals; the template-directed refolding model ('seeded polymerisation') and the inhibitor titration model. The former model has gained general acceptance and invokes the formation of oligomeric seeds that drive the structural alteration and polymerisation of soluble molecules of the prion protein thus forming the characteristic high molecular weight amyloid fibrils. Stable propagation of yeast prions thus requires continued generation of new prion seeding molecular entities (which we call propagons) and their efficient transmission to daughter cells at cell division. In this project we are exploiting a novel, stochastic modelling approach to establish the key molecular events in the propagation and transmission of the [PSI+] prion.

Our current models provide an important phenomenological description of how the [PSI+] prion is eliminated in the absence of a mechanism to generate new propagons. In this new project we are developing new mechanistic models that not only take into account the kinetics of prion protein polymerisation, but also polymer fragmentation in the growing yeast cell. To achieve this we are generating stochastic simulation models for yeast prion polymer kinetics and supporting this model building by experimentally establishing the values of the important model factors including the cellular levels of Sup35p and the key chaperone proteins Hsp104 and Sis1p, the number and sizes of Sup35p prion polymers and the rate of synthesis and turnover of Sup35p in its various cellular forms.

To evaluate the emerging simulation models we are also assessing the in vivo consequences of modulating levels of Sup35p, Hsp104 and Sis1p all of which are essential for [PSI+] propagation. One crucial parameter in our models is pi, the proportion of propagons transmitted to the daughter cell. We wish to identify factors that lead to a change in pi, particularly in relation to the number and length of Sup35p polymers in the cell. We also carry out model sensitivity and validation studies in the light of experimental data obtained in order to generate a definitive stochastic simulation model for yeast prion polymer kinetics in the dividing cell. This project involves a close interplay between bioscience-led research and integrated mathematical modelling with the aim of shedding new light on how infectious amyloids are generated and transmitted in vivo.

Researchers: Dr Wesley Naeimi (postdoc), Dr Vasileios Giagos (postdoc), Jintana Wongwigkarn (PhD student)

Collaborators: Professors Byron Morgan and Martin Ridout (School of Mathematics, Statistics and Actuarial Science, University of Kent)

Funded by: BBSRC

Induction of yeast prions by reactive oxygen species (ROS)


How yeast and mammalian prions form spontaneously into infectious amyloid-like structures is poorly understood at present yet the majority of cases of the human prion disease Creutzfeldt Jakob Disease (CJD) are sporadic i.e. without underlying infection or genetic change. The overall objective of this project is to establish the molecular mechanism by which 'sporadic' prion formation is triggered by oxidative stress and other environmental triggers using the well established and widely exploited yeast prion model.

We are using two different yeast prions in this study, namely [PSI+]/Sup35 and [PIN+]/Rnq1, and are focussing on the role of the Tsa1/Tsa2 peroxiredoxins (Prxs). Prxs are antioxidant enzymes that have multiple functions in stress protection and, in collaboration with the laboratory of Professor Chris Grant at the University of Manchester, we have recently shown that the two major cytoplasmic Prxs (that both are ribosome-associated) suppress oxidative stress-induced de novo formation of the[PSI+] prion. Using high throughput assays for de novo formation of the [PSI+] and [PIN+] prions, we are therefore defining the role of Tsa1/Tsa2 in prion formation.

These important new findings strongly implicated oxidative damage of Sup35 as an important trigger of the formation of the heritable prion conformation in yeast. Oxidative damage has also been implicated in the de novo formation of mammalian prions and a trigger for other protein misfolding diseases of man. We have recently established that direct oxidation of the Sup35 polypeptides lead to structural transitions favouring conversion to the transmissible amyloid-like form and hence plays a role in the mechanism of induction of de novo prion formation. These studies are also being extended to other disease-associated, amyloid-forming proteins expressed in yeast including alpha-synuclein. The overall aim of this project is to define the mechanism by which oxidative stress induces yeast prion formation de novo and also the misfolding of human amyloidogenic proteins.

Researchers: Dr Gemma Staniforth (postdoc)

Collaborator: Professor Chris Grant, Dr Vicki Doronina, University of Manchester

Funded by: BBSRC

The natural history of yeast prions

The [PSI+] and [URE3] prions modify the yeast cell phenotype without apparent detriment, suggesting that prions could also represent a novel form of epigenetic inheritance. What we must now establish is whether prions exist in S. cerevisiae strains isolated from a variety of ecosystems and natural environments and are not simply an artifact of 'domestication' of this species.

The main aim of this project is to establish whether [PSI+] and [PIN+], two different and well characterised prions, are present in a wide range of wild strains of S. cerevisiae isolated from 'natural' environments. We will also establish whether the [PSI+] and [PIN+] prions from laboratory strains can replicate in such wild strains and vice versa. The hypothesis that underpins this project is that the [PSI+] and [PIN+] prions can exist in wild strains of S. cerevisiae and that apparently 'prion-free' wild strains have the molecular machinery to replicate one or both prions. Our laboratory was the first to report that a yeast prion (in this case [PIN+]) is present in some wild strains of S. cerevisiae, but in that study we only looked at relatively atypical pathogenic strains isolated from immunocompromised human patients. Although widely viewed as a domesticated organism, nevertheless S. cerevisiae has been found in a variety of ecological niches including tree bark and the surface of fruits. Each niche represents a unique environment in which the organism has to adapt and retain viability and fertility. As first suggested by Susan Lindquist and her colleagues at MIT, the ability to modulate protein function in a reversible manner without the immediate need to fix changes in DNA sequence could be of benefit to the host both in short-term adaptation and in the longer term, for the evolution of new traits.

Researchers: Professor Mick Tuite

Collaborators: Professor Susan Lindquist (MIT-WIBR)

Funded by: The Leverhulme Trust

Yeast models of protein misfolding diseases

To facilitate the analysis of the cause and consequences of disease-associated protein misfolding, a number of 'neurodegenerative disease models' have been established in the budding yeast Saccharomyces cerevisiae. S. cerevisiae is a highly tractable but simple eukaryote that nevertheless has many of the protein misfolding and quality control mechanisms that exist in higher eukaryotes. A number of the high profile human neurodegenerative diseases described to date, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) are being successfully studied in yeast models. The main objective of using a yeast-based model approach to further our understanding of these diseases is to establish the molecular basis of the causation and pathology of what are a globally important group of diseases. For example, by genetically manipulating S. cerevisiae to accumulate misfolded proteins allows the molecular mechanisms important in the cellular folding machinery and the response to misfolded proteins, to be identified. The factors which trigger misfolding and the generation of the toxic entity associated with this misfolding can also be established in order to identify potential intervention strategies.
In this project we are looking at two different disease models to try and establish the associated mechanism(s) of proteotoxicity:

Amyotrophic Lateral Sclerosis (ALS), a non-transmissible neurodegenerative disease affecting the upper and lower motor neurons of the brain and spinal cord. The most common fALS-associated mutation occurs in the gene encoding superoxide dismutase 1 (SOD1), an enzyme that converts superoxide anions to hydrogen peroxide and oxygen thus protecting cells against oxidative damage. We have developed a model in which we have introduced disease-associated mutations into the yeast SOD1 protein and are using a range of cell biological and biochemical approaches to pinpoint the associated toxicity that we see in yeast.

Amyloid toxicity. Two 'model' amyloids are being used one of which (Rnq1p) is a native yeast prion protein. The other 'model' is a protein carrying a polyglutamine expansion and based on the Huntington Disease-associated huntingtin protein. By carrying out genetic and cell biological screens in yeast expressing the disease-associated forms of these proteins we are identifying how the cell responds to amyloid-induced toxicity and the cellular factors that can be manipulated to abrogate the toxicity.

Researchers: Emma Bastow (PhD student), Selena Li (PhD student)

Collaborators: Dr Campbell Gourlay (University of Kent)

Funded by: BBSRC

Heterozygous inhibition of the amyloid state

A number of single-site mutations have been identified in the yeast Sup35p prion protein that lead to a failure to propagate the [PSI+] prion. One of the interesting properties of these so-called 'PNM – [PSI+] no more - mutations is that the prion form cannot propagate in the heterozygous configuration i.e. in diploid cells expressing equal levels of both normal and mutant Sup35p. This state mimics what has been observed with CJD and other prion diseases when there is heterozygosity at the PrP-encoding locus. This is very easy to show in yeast by mating two strains with different SUP35 alleles and showing that the diploid produced is unable to propagate the [PSI+] prion state.

The amyloids formed by Aβ, tau, huntingtin, α-synuclein, serum amyloid A and numerous other proteins responsible for amyloidoses in humans may or may not be self-propagating and none has been found to have resistance polymorphisms in populations. There are good reasons for this lack which have nothing to do with whether 'resistance' mutations analogous to the SUP35-based PNM mutations, may occur. In this project we are exploring the hypothesis that resistance mutants can be found such that, as in prions, heterozygosity at certain sites may prevent the formation of a non-self-propagating amyloid state.

Researchers: Dr Brian Cox

Collaborators: Professor Mike Resnick

Funded by: The Leverhulme Trust


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PhD students:

  • Laura Petch
  • Elliot Piper Brown (joint with Dr Campbell Gourlay)
  • Niken Pam (joint with Dr Wei-Feng Xue)

Senior Researcher:

  • Dr Brian Cox
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Year 2

  • BI501 Gene Expression and Its Control (Module convenor)

Final Year

  • BI601 Skills for Biochemists
  • BI651 Skills for Biologists III
  • BI631 Skills for Biomedical Scientists II
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Member of Editorial Boards of

Deputy Chair of the Scientific Conferences Committee of the Microbiology Society.

Member of grant awarding committees:

  • BBSRC – Committee B (core member)
  • Leverhulme Trust
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Enquiries: Phone: +44 (0)1227 823743

School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ

Last Updated: 29/01/2018