1992　　　   BA in Chemistry, University of Cambridge, UK

1997　　　   PhD in Protein Chemistry, University of Cambridge

1996 - 1997  Post-Doctoral Research Associate, University of Cambridge

1997 - 2000  College Research Fellow, University of Cambridge

1999 - 2000  Chinese language study, National University of Singapore

2000 - 2003  1851 & Royal Society Research Fellow, CAS Institute of Biophysics, Beijing

2003 -           Principal Investigator, CAS Institute of Biophysics

2015  CAS Young International Scientific Collaborator Prize (with Prof. Tuomas Knowles, University of Cambridge)

2015  OBE for services to UK/China relations in the scientific field

2010  Beijing Municipal Technology Prize (1st Class, with Prof. Xiyun Yan, IBP & others)

The structure and function of a given protein are intimately related. A number of human diseases are due to protein misfolding or aggregation. Molecular chaperones play a crucial role in the complex quality control machinery of the cell, to ensure that proteins fold and assemble correctly, and to prevent accumulation of misfolded or aggregated proteins. Over the years, our laboratory has applied a multidisciplinary approach to study molecular mechanisms of amyloid assembly, as well as protein folding, post-translational modification, and quality control. Current research directions include:

1. Single molecule study of the molecular mechanisms of amyloid assembly

Single-molecule techniques provide a powerful approach to study the conformational distributions and dynamic changes of biomacromolecules, and to probe sparsely populated components in complex systems. We are studying the detailed mechanism of fibril assembly for functional and disease-related amyloids, in order to reveal the origins for the difference in toxicity between pathogenic and functional amyloid fibrils, and to understand how biological systems regulate protein folding and misfolding.

2. Biological properties of amyloid-based nanomaterials

We are also studying how the unique properties of amyloid - such as high strength, stability and tunable assembly - can be exploited in the design of novel nanomaterials with biological function.

3. Structure, conformational dynamics and function of molecular chaperones

We are using a combination of biochemistry, cell biology, single molecule and structural biology techniques to study the conformational dynamics of the molecular chaperones Hsp70 and Hsp40, in order to understand the detailed mechanisms by which they control protein folding and misfolding. We are also examining the role of post-translational modifications in regulating the structure and function of Hsp70.

Selected from a total of 85 papers

1. Wen, J., Hong, L., Krainer G., Yao, Q.Q., Knowles T.P.J., Wu, S.* & Perrett, S.* (2021) Conformational expansion of Tau in condensates promotes irreversible aggregation. J. Am. Chem. Soc. In press.

2. Zhang, H., Gong, W., Wu, S., & Perrett, S.* (2021) Studying protein folding in health and disease using biophysical approaches. Emerg. Top. Life Sci. 5, 29-38.

3. Yang, J., Gong, W., Wu, S., Zhang, H.* & Perrett, S.* (2021) PES inhibits human inducible Hsp70 by covalent targeting of cysteine residues in the substrate binding domain. J. Biol. Chem. 296, 100210.

4. Yang, J., Perrett, S., Wu, S.* (2021) Single molecule characterization of amyloid oligomers. Molecules 26, 948.

5. Yao, X., Chen, C., Wang, Y., Dong S., Liu, Y.J., Li, Y., Cui, Z., Gong, W., Perrett, S., Yao, L., Lamed, R., Bayer, E.A., Cui, Q., Feng, Y.G.* (2020) Discovery and mechanism of a pH-dependent dual-binding-site switch in the interaction of a pair of protein modules. Science Advances 6, eabd7182.

6. Yang, J., Dear, A.J., Yao, Q., Liu, Z., Dobson, C.M., Knowles, T.P.J., Wu, S.* & Perrett, S.* (2020) Amelioration of aggregate cytotoxicity by catalytic conversion of protein oligomers into amyloid fibrils. Nanoscale 12, 18663-18672.

7. Yang, J., Zhang, H.*, Gong, W., Liu, Z., Wu, H., Hu, W., Chen, X., Wang, L., Wu, S., Chen, C.* & Perrett, S.* (2020) S-Glutathionylation of human inducible Hsp70 reveals a regulatory mechanism involving the C-terminal α-helical lid. J. Biol. Chem. 295, 8302-8324.

8. Wu, S. Hong, L., Wang, Y., Yang, J., Yang J., Zhang, H. & Perrett, S.* (2020) A kinetic view of the conformational cycle of Hsp70 reveals the importance of the dynamic and heterogeneous nature of Hsp70 for its function. PNAS 117, 7814-7823.

9. Dear, A.J., Michaels, T.C.T., Meisl, G., Klenerman, D., Wu, S., Perrett, S., Linse, S., Dobson, C.M., and Knowles, T.P.J.* (2020) Kinetic diversity of amyloid oligomers. PNAS 117, 12087-12094.

10. Yao, Q., Hong, L., Wu, S.* & Perrett, S.* (2020) Distinct microscopic mechanisms for the accelerated aggregation of pathogenic Tau mutants revealed by kinetic analysis. PhysChemChemPhys 22, 241-7249.

11. Yang, J., Dear, A.J., Michaels, T.C.T., Dobson, C.M., Knowles, T.P.J.K.*, Wu, S.* & Perrett, S.* (2018). Direct observation of oligomerization by single molecule fluorescence reveals amulti-step aggregation mechanism for the yeast prion protein Ure2. J. Am. Chem. Soc., 140, 2493-2503.

12. Gong, W., Hu, W., Xu, L., Wu, H., Wu, S., Zhang, H., Wang, J., Jones, GW.* & Perrett, S.* (2018).The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast. J. Biol. Chem. 293, 17663-17675.

13. Xu, L., Gong, G.*, Cusack, S.A., Wu, H., Loovers, H.M., Zhang, H., Perrett, S. & Jones G.W.* (2018). The β6/β7 region of the Hsp70 substrate-binding domain mediates heat shock response and prion propagation. Cell. Mol. Life Sci., 75, 1445-1459.

14. Lou, F., Yang, J., Wu, S.* & Perrett, S.* (2017). A co-expression strategy to acheive labeling of individual subunits within a dimeric protein for single molecule analysis. ChemComm 53, 7971-8094.

15. Yang, W., Willemse J., Sawyer E.B., Lou F., Gong, W., Zhang, H., Gras, S.L.*, Claessen, D.* & Perrett, S.* (2017). The propensity of the bacterial rodlin protein RdlB to form amyloid fibrils determines its function in Streptomyces coelicolor. Scientific Reports 7, 42867.

16. Zhang, H., Yang, J., Si, W., Gong, W., Chen, C.* & Perrett, S.* (2016). Glutathionylation of the bacterial Hsp70 chaperone DnaK provides a link between oxidative stress and the heat shock response. J. Biol. Chem. 291, 6967-6981.

17. Zhou, X.M., Shimanovich, U., Herling, T.W., Wu, S., Dobson, C.M., Knowles, T.P.J.* & Perrett, S.* (2015) Enzymatically-active microgels from self-assembling protein nanofibrils for microflow chemistry. ACS Nano 9, 5772-5781.

18. Rees, J.S., Li, X.W., Perrett, S.*, Lilley, K.S.* & Jackson, A.P.* (2015) Protein neighbours and proximity proteomics. Molecular & Cellular Proteomics 14, 2848-2856. (Invited Review)

19. Wu, H., Gong, W., Yao, X., Wang, J., Perrett, S.* & Feng, Y.* (2015). Evolutionarily conserved binding of translationally-controlled tumor protein to eukaryotic elongation factor 1B. J. Biol. Chem. 290, 8694-710.

10. Zhou, X.M., Entwistle, A., Zhang, H., Jackson, A.P., Mason, T.O., Shimanovich, U., Knowles, T.P.J., Smith, A.T., Sawyer, E.B.* & Perrett, S.* (2014). Self-assembly of amyloid fibrils that display active enzymes. ChemCatChem 6, 1961-1968.

21. Li, X.W., Rees, J.S., Lilley, K.S., Howard, J.A., Zhang, H., Peng, X., Hamaia, S.W., Farndale, R.W., Perrett, S.* & Jackson, A.P.* (2014). New insights into the DT40 B cell receptor cluster using a proteomic proximity labeling assay. J. Biol. Chem. 289, 14434-14447. (Highlighted as a "Key Scientific Article" in Global Medical Discovery. Highlighted in Bulletin of the Chinese Academy of Sciences. Chapter invited for Current Protocols. Review invited for Mol. Cell. Proteom.)

22. Gong, W, Wang, J., Perrett, S.* & Feng, Y.* (2014). RBBP1 has an interdigitated double Tudor domain with DNA-binding activity. J. Biol. Chem. 289, 4882-4895.

23. Xu, L.Q., Wu, S., Buell, A.K., Cohen, S.I.A., Chen, L.J., Hu, W.H., Cusack, S.A., Itzhaki, L.S., Zhang, H.*, Knowles, T.P.J., Dobson, C.M., Welland, M.E., Jones, G.W. & Perrett S.* (2013). Influence of specific Hsp70 domains on Ure2 fibril formation in vitro. Phil. Trans. Roy. Soc. B 368, 20110410. (Invited submission)

24. Zhu, M., Perrett, S. & Nie, G.* (2013). Understanding the particokinetics of engineered nanomaterials for safe and effective therapeutic applications. SMALL 9, 1619-34.

25. Truman, A.W., Kristjansdottir, K., Wolfgeher, D., Hasin, N., Polier, S., Zhang, H., Perrett, S., Prodromou, C., Jones, G.W. & Kron, S.J.* (2012). CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell cycle progression. CELL 151, 1308-1318.

26. Sawyer, E.B., Claessen D., Gras, S.L. & Perrett, S.* (2012) Exploiting amyloid: how and why bacteria use cross-β fibrils. Biochem. Soc. Trans. 40, 728-34. (Invited Review)

27. Chen, L.J., Sawyer, E.B. & Perrett, S.* (2011). The yeast prion protein Ure2: insights into the mechanism of amyloid formation. Biochem. Soc. Trans. 39, 1359-1364. (Invited review)

28. Li, Y., Zhou, Y., Wang, H.Y., Perrett, S., Zhao, Y.,* Tang, Z.* & Nie, G.* (2011). Chirality of gluthathione surface coating affects the cytotoxicity of quantum dots. Angew. Chem. Int. Ed. Engl. 50, 5860-5864. (Highlighted in Nature Materials (2011) 10, 480.)

29. Wang, Y.Q., Buell, A.K., Wang, X.Y., Welland M.E., Dobson, C.M., Knowles, T.P.J.* & Perrett, S.* (2011). Relationship between prion propensity and the rates of individual molecular steps of fibril assembly. J. Biol. Chem. 286, 12101-12107. (On the Cover.)

30. Zhang, H., Xu, L.Q. & Perrett, S.* (2011). Studying the effects of chaperones on amyloid fibril formation. Methods 53, 285-294. (Invited Review)

31. Zhang, Z.R. & Perrett, S.* (2009). Novel glutaredoxin activity of the yeast prion protein Ure2 reveals a native-like dimer within fibrils. J. Biol. Chem. 284, 14058-14067.

32. Fei, L. & Perrett, S.* (2009). Disulfide bond formation significantly accelerates the assembly of Ure2p fibrils due to proximity of a potential amyloid stretch. J. Biol. Chem. 284, 11134-11141.

33. Zhang, H., Loovers, H.M., Xu, L.Q., Wang, M., Rowling, P.J.E., Itzhaki, L.S., Gong, W., Zhou, J.M., Jones, G.W. & Perrett, S.* (2009). Alcohol oxidase (AOX1) from Pichia pastoris is a novel inhibitor of prion propagation and a potential ATPase. Mol. Microbiol. 71, 702-716.

34. Perrett, S.* & Jones, G.W.* (2008). Insights into the mechanism of prion propagation. Curr. Opin. Struct. Biol. 18, 52-59. (Invited Review)

35. Gao, L., Zhuang, J., Nie, L., Zhang, J., Gu, N., Wang, T., Perrett, S.* & Yan, X.* (2007). Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nature Nanotechnology 2, 577-583. (Article)　

• Books

1. Perrett S., A.K. Buell & T.P.J.K. Knowles (Editors) “Biological and Bio-inspired Nanomaterials”, 2019, Springer Nature. ISBN: 978-981-13-9790-5.

2. Sunde M., Chapman M., Otzen D. & Perrett S. (Editors), “Functional Amyloids” Biomacromolecules vol. 7, 2017, MDPI. ISSN: 2218-273X

3. Perrett S. (Editor), “Amyloids in Health and Disease” Essays in Biochemistry vol. 56 (248 pages), 2014, Portland Press. ISBN: 781855781924

• Book Chapters

1. Roode, L.W.Y., Schimanovich, U., Wu, S., Perrett, S. & Knowles, T.P.J. “Protein microgels from amyloid fibril networks.” Biological and Bio-inspired Nanomaterials, Advances in Experimental Medicine and Biology vol. 1174 (Chapter 7, p. 223-263), 2019, Springer Nature.

2. Rees, J.S., Li, X.W., Perrett, S., Lilley, K.S. & Jackson, A.P. “Selective proteomic proximity labeling assay using tyramide (SPPLAT): A quantitative method for the proteomic analysis of localised membrane-bound protein clusters.” Current Protocols in Protein Science vol. 88 (p.19.27.1-19.27.18), 2017, Wiley.

 

(From Sarah Perrett, July 2, 2021)