Faculty of Health and Life Sciences

Dr Helen Dawe

Dr Helen Dawe

Honorary Senior Lecturer

 H.R.Dawe@exeter.ac.uk

 

Overview

I am a molecular cell biologist with interests in cell polarity, cell morphogenesis and the cytoskeleton. My research focuses on how eukaryotic flagella/cilia are built, and how this goes wrong in human inherited disease. I am particularly interested in the early stages of ciliogenesis: centrosome migration and docking at the cell surface, and how these go awry in Meckel-Gruber and Joubert syndromes. I am a member of the Cell Biology research group.

Qualifications

1999-2003 PhD Molecular Cell Biology, MRC Laboratory for Molecular Cell Biology, University of London
1995-1999 BSc (Hons) Biochemistry with Industrial Experience, University of Manchester

Career

2009-2021 Lecturer in Cell Biology, University of Exeter
2008-2009 University Research Lecturer, University of Oxford
2006-2009 Beit Memorial Fellow, University of Oxford, and Fellow of Brasenose College Oxford
2003-2006 Postdoctoral Research Associate, University of Oxford

Research group links

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Research

Research interests

Eukaryotic cilia and flagella are remarkably conserved, both at the structural and functional levels, from evolutionarily ancient unicellular eukaryotes to man and are adapted to carry out diverse roles. Almost every cell in the human body can form a cilium or flagellum, either motile or non-motile. Motile cilia move fluids past epithelial cell layers in multicellular organisms; however, non-motile primary cilia are the most common type of cilia in the body. The roles of primary cilia were unclear but the recent identification of many inherited disorders involving aberrant ciliary function, termed “ciliopathies”, has changed this and primary cilia are now known as sensory organelles, acting both as chemo- or mechanosensors and transducers of signals that regulate key developmental signalling pathways. My lab focuses on the severe ciliopathy Meckel Gruber syndrome. We use a combination of patient-derived cell lines, post-genomic technologies, classical cell biology and genetics to give insight into the molecular cell biology of the disease. We are currently studying the roles that two proteins, TMEM67 and TMEM216, play in organisation of the actin and microtubule cytoskeletons during cell migration.

Research projects

Current research falls into the following overlapping projects:

  • the mechanism of centrosome migration to the apical membrane during ciliogenesis of primary cilia
  • the molecular cell biology of Meckel-Gruber and Joubert syndromes
  • the role of MKS proteins in non-ciliated cells
  • the role of cilia in setting up the left-right axis in invertebrates

Research networks

Dr Colin Johnson (Leeds Institute for Molecular Medicine)
Dr John Sayer (University of Newcastle)
Prof. Keith Gull (University of Oxford)
Dr Sue Vaughan (Oxford Brookes University)
Dr Lorna Harries (Exeter Medical School)

Research grants

  • 2011 MRC
    New Investigator Award "The Role of Meckel-Gruber Syndrome Proteins in Cell Migration"

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Publications

Journal articles

Latorre E, Birar VC, Sheerin AN, Jeynes JCC, Hooper A, Dawe HR, Melzer D, Cox LS, Faragher RGA, Ostler EL, et al (2017). Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC Cell Biol, 18(1). Abstract.  Author URL.
Barker AR, McIntosh KV, Dawe HR (2016). Centrosome positioning in non-dividing cells. Protoplasma, 253(4), 1007-1021. Abstract.  Author URL.
Pratt MB, Titlow JS, Davis I, Barker AR, Dawe HR, Raff JW, Roque H (2016). Drosophila sensory cilia lacking MKS proteins exhibit striking defects in development but only subtle defects in adults. J Cell Sci, 129(20), 3732-3743. Abstract.  Author URL.
Martin-Urdiroz M, Deeks MJ, Horton CG, Dawe HR, Jourdain I (2016). The Exocyst Complex in Health and Disease. Frontiers in Cell and Developmental Biology, 4
Barker AR, Renzaglia KS, Fry K, Dawe HR (2014). Bioinformatic analysis of ciliary transition zone proteins reveals insights into the evolution of ciliopathy networks. BMC Genomics, 15(1). Abstract.  Author URL.
Locke JM, Da Silva Xavier G, Dawe HR, Rutter GA, Harries LW (2014). Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion. Diabetologia, 57(1), 122-128. Abstract.
Barker AR, Thomas R, Dawe HR (2014). Meckel-Gruber syndrome and the role of primary cilia in kidney, skeleton, and central nervous system development. Organogenesis, 10(1), 96-107. Abstract.  Author URL.
Barker AR, McIntosh K, Dawe HR (2013). Meckel-Gruber syndrome proteins are required for actin cytoskeleton organisation and directional cell migration. MOLECULAR BIOLOGY OF THE CELL, 24  Author URL.
Adams M, Simms RJ, Abdelhamed Z, Dawe HR, Szymanska K, Logan CV, Wheway G, Pitt E, Gull K, Knowles MA, et al (2012). A meckelin-filamin a interaction mediates ciliogenesis. Hum Mol Genet, 21(6), 1272-1286. Abstract.  Author URL.
Adams M, Simms RJ, Abdelhamed Z, Dawe HR, Szymanska K, Logan CV, Wheway G, Pitt E, Gull K, Knowles MA, et al (2012). A meckelin-filamin a interaction mediates ciliogenesis. Human Molecular Genetics, 21(6), 1272-1286. Abstract.
Cheng Y-Z, Eley L, Hynes A-M, Overman LM, Simms RJ, Barker A, Dawe HR, Lindsay S, Sayer JA (2012). Investigating embryonic expression patterns and evolution of AHI1 and CEP290 genes, implicated in Joubert syndrome. PLoS One, 7(9). Abstract.  Author URL.
Dawe H, Pitcher D, Barker A, Moles M (2012). MKS proteins regulate centrosome positioning during cell migration. Cilia, 1(Suppl 1).
Simms RJ, Hynes AM, Eley L, Inglis D, Chaudhry B, Dawe HR, Sayer JA (2012). Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain, retinal, and renal development. Cellular and Molecular Life Sciences, 69(6), 993-1009. Abstract.
Simms RJ, Hynes AM, Eley L, Inglis D, Chaudhry B, Dawe HR, Sayer JA (2012). Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain, retinal, and renal development. Cell Mol Life Sci, 69(6), 993-1009. Abstract.  Author URL.
Thompson H, Shaw MK, Dawe HR, Shimeld SM (2012). The formation and positioning of cilia in Ciona intestinalis embryos in relation to the generation and evolution of chordate left-right asymmetry. Dev Biol, 364(2), 214-223. Abstract.  Author URL.
Vaughan S, Dawe HR (2011). Common themes in centriole and centrosome movements. Trends Cell Biol, 21(1), 57-66. Abstract.  Author URL.
Gluenz E, Höög JL, Smith AE, Dawe HR, Shaw MK, Gull K (2010). Beyond 9+0: noncanonical axoneme structures characterize sensory cilia from protists to humans. FASEB J, 24(9), 3117-3121. Abstract.  Author URL.
Adams M, Dawe H, Wheway G, Szymanska K, Logan C, Noegel A, Gull K, Johnson C (2009). 16-P005 Mutations in the lethal ciliopathy Meckel–Gruber syndrome alter the subcellular distribution of actin-binding proteins and disrupt the actin cytoskeleton. Cells and Development, 126
Thompson H, Dawe H, Shimeld S (2009). 16-P028 the role of cilia in the development of left–right asymmetry. Cells and Development, 126
Dawe HR, Adams M, Wheway G, Szymanska K, Logan CV, Noegel AA, Gull K, Johnson CA (2009). Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of the actin cytoskeleton. J Cell Sci, 122(Pt 15), 2716-2726. Abstract.  Author URL.
Dawe HR, Gluenz E (2009). The tale of the trypanosome tail. Biologist, 56(4), 216-220.
Dawe HR, Farr H, Gull K (2007). Centriole/basal body morphogenesis and migration during ciliogenesis in animal cells. J Cell Sci, 120(Pt 1), 7-15. Abstract.  Author URL.
Dawe HR, Smith UM, Cullinane AR, Gerrelli D, Cox P, Badano JL, Blair-Reid S, Sriram N, Katsanis N, Attie-Bitach T, et al (2007). The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum Mol Genet, 16(2), 173-186. Abstract.  Author URL.
Dawe HR, Shaw MK, Farr H, Gull K (2007). The hydrocephalus inducing gene product, Hydin, positions axonemal central pair microtubules. BMC Biol, 5 Abstract.  Author URL.
Broadhead R, Dawe HR, Farr H, Griffiths S, Hart SR, Portman N, Shaw MK, Ginger ML, Gaskell SJ, McKean PG, et al (2006). Flagellar motility is required for the viability of the bloodstream trypanosome. Nature, 440(7081), 224-227. Abstract.  Author URL.
Dawe HR, Farr H, Portman N, Shaw MK, Gull K (2005). The Parkin co-regulated gene product, PACRG, is an evolutionarily conserved axonemal protein that functions in outer-doublet microtubule morphogenesis. J Cell Sci, 118(Pt 23), 5421-5430. Abstract.  Author URL.
Dawe HR, Minamide LS, Bamburg JR, Cramer LP (2003). ADF/cofilin controls cell polarity during fibroblast migration. Curr Biol, 13(3), 252-257. Abstract.  Author URL.
Cramer LP, Briggs LJ, Dawe HR (2002). Use of fluorescently labelled deoxyribonuclease I to spatially measure G-actin levels in migrating and non-migrating cells. Cell Motil Cytoskeleton, 51(1), 27-38. Abstract.  Author URL.

Conferences

Mseka T, Dawe HR, Bamburg JR, Cramer LP (2004). Actin filament depolymerization and microtubules control sequential actin dynamic steps to initiate cell polarity.  Author URL.

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External Engagement and Impact

Editorial responsibilities

Reviewer for Journal of Cell Science, Journal of Cell Biology, Human Molecular Genetics


Invited lectures

2011 Marie Curie Regenerative medicine symposium, Bath

2008 1st EMBO Conference on Centrosomes and Spindle Pole Bodies

2007  FASEB Summer Research Conference “The Biology of Cilia and Flagella”

Given invited seminars at 14 UK universities & research institutes

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Teaching

Year 2
BIO2088 Advanced Cell Biology

Year 3
BIO3077 Frontiers in Molecular Cell Biology

Modules

2023/24

Information not currently available


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Supervision / Group

Research Fellows

  • Amy Barker

Postgraduate researchers

Alumni

  • David Pitcher
  • Helen Thompson DPhil student, University of Oxford

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