Professor Kathryn Ayscough
School of Biosciences
Professor of Molecular Cell Biology
- Profile
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- 2021-Present: Professor, Biomedical Science
- 2016-2021: Head of Department, Biomedical Science
- 2012-2016: Professor, Deputy Head of Biomedical Science
- 2008-2012: Professor and MRC Senior Research Fellow. Department of Molecular Biology and Biotechnology, University of Sheffield
- 2003–2008: MRC Senior Research Fellow. Department of Molecular Biology and Biotechnology, University of Sheffield
- 1999–2003: MRC Senior Research Fellow, Department of Biochemistry, University of Glasgow
- 1996–1999: Wellcome Trust Career Development Fellow, Department of Biochemistry, University of Dundee
- 1993-1999: Wellcome International Travelling Fellow, University of California, Berkeley, USA. Supervisor David Drubin
- 1989–1993: PhD Imperial Cancer Research Fund (now CRUK) and University College London. Supervisor Graham Warren
- 1985-1989: BA MA(Oxon) Biochemistry, University of Oxford. 1st Class.
- Research interests
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The main research focus of my lab is to understand the mechanisms governing cell organization and architecture. We are currently addressing how one of the key elements of the cytoskeleton (actin) can initiate filaments formation and how these filaments can then be organized to allow inward bending of the plasma membrane. This invagination process is called endocytosis and allows cells to regulate their cell surface composition in response to environmental signals. We are also aiming to understand how the process of endocytosis is coupled to the invasion and survival properties of the human fungal pathogen Candida albicans.
The role of the actin cytoskeleton in membrane trafficking and cell organization
Cells are the basic unit of life and all organisms are composed of one or more cells. Central to the functioning of many cells, including human cells, is the internal skeleton, or cytoskeleton. This cytoskeleton is required for cells to have certain shapes that are often a necessary part of their functioning. However, unlike our own body skeleton that is static, the cytoskeleton is able to remodel itself to change cell shape, or allow a cell to move.
One of the most important proteins in the cytoskeleton is called actin. It is an amazing protein because it is almost the same now as hundreds of millions of years ago, long before humans, or even vertebrates existed. Staying so similar over time is called evolutionary conservation. Proteins that are very important to cell functioning are the most highly conserved. Actin is a protein that can join together with other actin proteins to form long lines or filaments. These filaments can be organised by other proteins to form large structures that are part of the cytoskeleton.
We are interested in how this protein is controlled in cells and in particular, we are trying to determine how the filaments can be started from single actin proteins in a process called nucleation. We are also aiming to understand how force can be generated by these filaments to help inward bending of the outer membrane of the cell to let parts of the membrane to be pinched off (internalised) This process, called endocytosis allows the surface composition of the cell to be effectively regulated.
Scientific questions we are addressing:
- How are new actin filaments initiated at cell membranes?
- How is actin nucleation regulated in cells?
- What mechanisms ensure that endocytosis is a unidirectional process?
- How does actin function in membrane scission?
- What is the importance of endocytosis for virulence of the pathogenic fungus Candida albicans?
Techniques we use:
- Molecular biology: PCR, cloning, in vitro mutagenesis
- Biochemistry: protein expression and purification, binding assays including microscale thermophoresis; immunoprecipitation and GST pull down; lipid and liposome binding, actin polymerization assays, negative staining and electron microscopy analysis of actin filaments
- Genetics: S. cerevisiae and Candida albicans gene deletion and epitope tagging, growth, phenotypic analysis, strain crossing, tetrad dissection
- Cell Biology and microscopy: dual colour live cell imaging including quantitative analysis and patch tracking using Deltavision microscope; yeast endocytosis assays and vital staining for mitochondria and vacuoles.
- Electron microscopy, in collaboration with Per Bullough (University of Sheffield); Martin Goldberg, (Durham University)
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth in Candida albicans.. mBio, 10(2). View this article in WRRO
- Amino acid substitution equivalent to human chorea-acanthocytosis I2771R in yeast Vps13 protein affects its binding to phosphatidylinositol 3-phosphate. Human Molecular Genetics, 26(8), 1497-1510. View this article in WRRO
- Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP. PLoS ONE, 11(9). View this article in WRRO
- A Dynamin-Actin Interaction Is Required for Vesicle Scission during Endocytosis in Yeast. Current Biology, 25(7), 868-878. View this article in WRRO
- Yeast Endocytic Adaptor AP-2 Binds the Stress Sensor Mid2 and Functions in Polarized Cell Responses. Traffic, 15(5), 546-557. View this article in WRRO
- A novel actin-binding motif in Las17/WASP nucleates actin filaments independently of Arp2/3.. Curr Biol, 23(3), 196-203.
All publications
Journal articles
- The dynamin Vps1 mediates Atg9 transport to the sites of autophagosome formation. Journal of Biological Chemistry, 299(5), 104712-104712.
- A ruthenium(II) polypyridyl complex disrupts actin cytoskeleton assembly and blocks cytokinesis. Angewandte Chemie International Edition, 61(27).
- Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis. Scientific Reports, 11. View this article in WRRO
- The Pex3–Inp1 complex tethers yeast peroxisomes to the plasma membrane. Journal of Cell Biology, 219(10). View this article in WRRO
- The AP-2 endocytic adaptor complex in Candida albicans morphology and virulence. Access Microbiology, 1(9).
- AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth in Candida albicans.. mBio, 10(2). View this article in WRRO
- Yeast model based study identified myosin and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis. Disease Models & Mechanisms, 12(1). View this article in WRRO
- Disruption of the plant-specific CFS1 gene impairs autophagosome turnover and triggers EDS1-dependent cell death. Scientific Reports, 7(1). View this article in WRRO
- Amino acid substitution equivalent to human chorea-acanthocytosis I2771R in yeast Vps13 protein affects its binding to phosphatidylinositol 3-phosphate. Human Molecular Genetics, 26(8), 1497-1510. View this article in WRRO
- Forty years on: clathrin-coated pits continue to fascinate. Molecular Biology of the Cell, 28(7), 843-847. View this article in WRRO
- WASP family proteins, more than Arp2/3 activators. Biochemical Society Transactions, 44(5), 1339-1345. View this article in WRRO
- Phosphatidylinositol-3-phosphate regulates response of cells to proteotoxic stress. The International Journal of Biochemistry & Cell Biology, 79, 494-504. View this article in WRRO
- Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP. PLoS ONE, 11(9). View this article in WRRO
- Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1. Microbial Cell, 3(4), 147-158. View this article in WRRO
- Phosphorylation Regulates the Endocytic Function of the Yeast Dynamin-Related Protein Vps1. Molecular and Cellular Biology, 36(5), 742-755. View this article in WRRO
- Distinct Actin and Lipid Binding Sites in Ysc84 Are Required during Early Stages of Yeast Endocytosis. PLOS ONE, 10(8). View this article in WRRO
- A Charge Swap mutation E461K in the yeast dynamin Vps1 reduces endocytic invagination. Communicative & Integrative Biology, 8(4), e1051274-e1051274. View this article in WRRO
- A Dynamin-Actin Interaction Is Required for Vesicle Scission during Endocytosis in Yeast. Current Biology, 25(7), 868-878. View this article in WRRO
- Function and interactions of the Ysc84/SH3yl1 family of actin- and lipid-binding proteins. Biochemical Society Transactions, 43(1), 111-116. View this article in WRRO
- An Abp1-Dependent Route of Endocytosis Functions when the Classical Endocytic Pathway in Yeast Is Inhibited. PLoS ONE, 9(7). View this article in WRRO
- Yeast Endocytic Adaptor AP-2 Binds the Stress Sensor Mid2 and Functions in Polarized Cell Responses. Traffic, 15(5), 546-557. View this article in WRRO
- Apm4, the mu subunit of yeast AP-2 interacts with Pkc1, and mutation of the Pkc1 consensus phosphorylation site Thr176 inhibits AP-2 recruitment to endocytic sites. Communicative & Integrative Biology, 7(2), e28522-e28522. View this article in WRRO
- Dynamin−SNARE interactions control trans-SNARE formation in intracellular membrane fusion. Nature Communications, 4(1). View this article in WRRO
- A novel actin-binding motif in Las17/WASP nucleates actin filaments independently of Arp2/3.. Curr Biol, 23(3), 196-203.
- Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells.. BMC Cell Biol, 13, 1. View this article in WRRO
- Yeast Dynamin Vps1 and Amphiphysin Rvs167 Function Together During Endocytosis. Traffic, 13(2), 317-328.
- Yeast dynamin Vps1 and amphiphysin Rvs167 function together during endocytosis.. Traffic, 13(2), 317-328.
- Expression of Vps1 I649K, a self-assembly defective yeast dynamin, leads to formation of extended endocytic invaginations. Communicative & Integrative Biology, 4(1), 115-117.
- Expression of Vps1 I649K a self-assembly defective yeast dynamin, leads to formation of extended endocytic invaginations.. Commun Integr Biol, 4(1), 115-117.
- A role for the dynamin-like protein Vps1 during endocytosis in yeast.. J Cell Sci, 123(Pt 20), 3496-3506.
- The yeast actin cytoskeleton and its function in endocytosis. Fungal Biology Reviews, 24(1-2), 37-46.
- Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan.. J Cell Sci, 123(Pt 1), 118-127.
- Membrane rafts are involved in intracellular miconazole accumulation in yeast cells.. J Biol Chem, 284(47), 32680-32685.
- Differential requirements for actin during yeast and mammalian endocytosis.. Nature Cell Biology, 11(8), 1039-1042. View this article in WRRO
- Functions of actin in endocytosis.. Cell Mol Life Sci, 66(13), 2049-2065.
- Methyl beta-cyclodextrin reduces accumulation of reactive oxygen species and cell death in yeast.. Free Radic Biol Med, 46(11), 1478-1487.
- The WASP homologue Las17 activates the novel actin-regulatory activity of Ysc84 to promote endocytosis in yeast.. Mol Biol Cell, 20(6), 1618-1628.
- Whi2p links nutritional sensing to actin-dependent Ras-cAMP-PKA regulation and apoptosis in yeast.. J Cell Sci, 122(Pt 5), 706-715.
- Interactions between the yeast SM22 homologue Scp1 and actin demonstrate the importance of actin bundling in endocytosis.. J Biol Chem, 283(22), 15037-15046.
- Yeast Arf3p modulates plasma membrane PtdIns(4,5)P2 levels to facilitate endocytosis.. Traffic, 9(4), 559-573.
- Miconazole induces changes in actin cytoskeleton prior to reactive oxygen species induction in yeast.. J Biol Chem, 282(30), 21592-21597.
- Nucleocytoplasmic trafficking is required for functioning of the adaptor protein Sla1p in endocytosis.. Traffic, 8(4), 347-358.
- Immunological methods. METHOD MICROBIOL, 36, 241-268.
- Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae.. Mol Cell Biol, 26(17), 6487-6501.
- Apoptosis in yeast--mechanisms and benefits to a unicellular organism.. Mol Microbiol, 62(6), 1515-1521.
- Actin regulation in endocytosis.. J Cell Sci, 119(Pt 22), 4589-4598.
- Interactions between Sla1p, Lsb5p and Arf3p in yeast endocytosis.. Biochem Soc Trans, 33(Pt 6), 1273-1275.
- A role for actin in aging and apoptosis.. Biochem Soc Trans, 33(Pt 6), 1260-1264.
- The actin cytoskeleton in ageing and apoptosis.. FEMS Yeast Res, 5(12), 1193-1198.
- A role for actin in aging and apoptosis. Biochemical Society Transactions, 33(6), 1260-1264.
- Defining protein modules for endocytosis.. Cell, 123(2), 188-190.
- Coupling actin dynamics to the endocytic process in Saccharomyces cerevisiae.. Protoplasma, 226(1-2), 81-88.
- The actin cytoskeleton: a key regulator of apoptosis and ageing?. Nat Rev Mol Cell Biol, 6(7), 583-589.
- Identification of an upstream regulatory pathway controlling actin-mediated apoptosis in yeast.. J Cell Sci, 118(Pt 10), 2119-2132.
- Lsb5p interacts with actin regulators Sla1p and Las17p, ubiquitin and Arf3p to couple actin dynamics to membrane trafficking processes.. Biochem J, 387(Pt 3), 649-658.
- Actin-binding proteins.. J Cell Sci, 118(Pt 4), 651-654.
- Two billion years of actin. Meeting on cytoskeletal dynamics: from cell biology to developmental disease.. EMBO Rep, 5(10), 947-952.
- A role for the actin cytoskeleton in cell death and aging in yeast.. J Cell Biol, 164(6), 803-809. View this article in WRRO
- Endocytosis: Actin in the driving seat. CURR BIOL, 14(3), R124-R126.
- SCP1 encodes an actin-bundling protein in yeast.. Biochem J, 375(Pt 2), 287-295.
- An interaction between Sla1p and Sla2p plays a role in regulating actin dynamics and endocytosis in budding yeast.. J Cell Sci, 116(Pt 12), 2551-2564.
- The Ark1/Prk1 family of protein kinases. Regulators of endocytosis and the actin skeleton.. EMBO Rep, 4(3), 246-251.
- Novel proteins linking the actin cytoskeleton to the endocytic machinery in Saccharomyces cerevisiae.. Mol Biol Cell, 13(10), 3646-3661.
- Endocytosis and the development of cell polarity in yeast require a dynamic F-actin cytoskeleton.. Curr Biol, 10(24), 1587-1590.
- Latrunculin alters the actin-monomer subunit interface to prevent polymerization.. Nat Cell Biol, 2(6), 376-378.
- Sla1p is a functionally modular component of the yeast cortical actin cytoskeleton required for correct localization of both Rho1p-GTPase and Sla2p, a protein with talin homology.. Mol Biol Cell, 10(4), 1061-1075.
- [2] Use of latrunculin-A, an actin monomer-binding drug, 18-25.
- A role for the yeast actin cytoskeleton in pheromone receptor clustering and signalling.. Curr Biol, 8(16), 927-930.
- In vivo functions of actin-binding proteins.. Curr Opin Cell Biol, 10(1), 102-111.
- High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A.. J Cell Biol, 137(2), 399-416. View this article in WRRO
- A role for the actin cytoskeleton of Saccharomyces cerevisiae in bipolar bud-site selection.. J Cell Biol, 136(1), 111-123. View this article in WRRO
- ACTIN: general principles from studies in yeast.. Annu Rev Cell Dev Biol, 12, 129-160.
- Localization of an alpha 1,2 galactosyltransferase activity to the Golgi apparatus of Schizosaccharomyces pombe.. Mol Biol Cell, 5(5), 519-528.
- Inhibition of protein synthesis disrupts the Golgi apparatus in the fission yeast, Schizosaccharomyces pombe.. Yeast, 10(1), 1-11.
- Cold-sensitive mutants of p34cdc2 that suppress a mitotic catastrophe phenotype in fission yeast.. Mol Gen Genet, 232(3), 344-350.
- Spindle Position Checkpoint Kinase Kin4 Regulates Organelle Transport in Saccharomyces cerevisiae. Biomolecules, 13(7), 1098-1098.
- Mutation of key lysine residues in the Insert B region of the yeast dynamin Vps1 disrupts lipid binding and causes defects in endocytosis. PLOS ONE, 14(4), e0215102-e0215102.
- Guidelines and recommendations on yeast cell death nomenclature. Microbial Cell, 5(1), 4-31. View this article in WRRO
Conference proceedings papers
- Meeting Report from the 55th Harden Conference: Dynamics of Membrane Traffic, 26-29th August 2002. Traffic, Vol. 4(1) (pp 49-54)
Datasets
- AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth in Candida albicans.. mBio, 10(2). View this article in WRRO
- Research group
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Research theme: Cell Biology.
Post doc: Ellen Allwood
PhD students: Sarah Gratton and Stella Christou
- Grants
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- BBRSC Project Grant, (2016 –2019) £638,000. Elucidating the molecular mechanism of Arp2/3-independent actin nucleation by WASP family proteins. Principal investigator.
- BBSRC Infrastructure Award (2013) A Quantitative Biomolecular Interaction Suite. Co-applicant.
- MRC Imaging Initiative (Sheffield IMAging) (2013) Co-applicant
- BBSRC Project Grant (2013 – 2016) Elucidating the mechanism of endocytic invagination and scission. Principal investigator
- BBSRC Project Grant (2012 – 2015) £602,000. Defining factors that ensure unidirectionality of endocytosis. Principal investigator
- Yorkshire Cancer Research (2010-2011) –Regulation of podosome/invadopodia dynamics in prostate cancer cells. Co-applicant.
- BBSRC Project Grant. (2009 - 2012). Endocytic Invagination and Vesicle Scission - interplay between Dynamin homologues and Amphiphysins in Budding Yeast. Principal investigator.
- MRC Senior non-clinical Fellowship Renewal (2007-2012) - £1,142,297. The Role of Actin in Cell Homeostasis.
- Teaching activities
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Lecture on BMS 242/243; L3, L4 projects; MSc projects
- Professional activities and memberships
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Grant awarding panels:
- BBSRC Responsive Mode Grant Panel D (2014-2019)
- The Wellcome Trust (Molecules, Genes and Cells Committee) 2006-2009
- Wolfson-Royal Society Infrastructure Awards (2012)
Grant panels:
- MRC Senior non-clinical Fellow (2001 – 2012)
- Editorial Board for the international journals Molecular Biology of the Cell, Cytoskeleton and F1000 Research
- Faculty of 1000 member (Cytoskeleton panel from 2010)
- Scientific Advisory Board, Biological Sciences, Durham University
Learned Societies:
- Fellow of the Royal Society of Biology
- British Society for Cell Biology - Executive Committee (1998 - 2004)
- Biochemical Society Theme Panel IV Cells (2011-2014)