David Bryant - Molecular Control of Epithelial Polarity

University of Glasgow / Beatson Associate

Introduction

BryantD

Cells of many tissues are polarised, collectively forming configurations tailored to the needs of a tissue. A common feature of most cancers of epithelial origin is the loss of normal tissue architecture. Despite advances in identifying signalling pathways and genetic alterations involved in driving cancer progression, little is known about this very basic, yet fundamental question: how do such changes affect cell polarity to turn highly organised tissues into disarrayed tumours?

bryant model of polarity

Our lab focuses on how cell polarity is controlled in prostate tumours. Our efforts are focused on two molecular pathways: the role of ARF GTPases (and their regulators and effectors, which we call the 'ARF regulome'), and the role of the cell surface protein, Podocalyxin. Both molecules are highly overexpressed in metastatic prostate cancer tumours.

Our lab focuses on molecular imaging studies to characterise how these molecules control normal and aberrant prostate epithelial polarisation. Our ultimate aim is to investigate these molecules as potential future biomarkers of prostate cancer in patients, and possible targets for future therapeutic interventions.


University of Glasgow webpage

Google Scholar Account

PhD studentship position available in the Bryant Lab to use advanced microscopy to understand tumour invasion and metastasis. Look for the following project, under the Basic Bioscience Underpinning Health heading: "Seeing is believing: using advanced microscopy to analyse how mini-tumours move".

Lab Report

 icon Bryant Lab Report

Research Highlights

  • Extensive molecular characterisation of how cells know to orient their apical surfaces in the correct direction. Importantly, this work uncovers one way by which the extracellular matrix determines whether groups of epithelial cells become invasive or form a lumen (Dev Cell 2014)
  • Molecular characterisation of how cell polarity rearrangements can function as an innate response system of epithelial barriers to a bacterial pathogen challenge (p. aeruginosa) (Cell Host Microbe 2014)
  • First molecular description of the membrane trafficking and polarity rearrangements required to form an apical surface and lumen de novo. Our findings have been recapitulated in many other systems, showing that we uncovered a fundamentally conserved biological process (Nat Cell Biol 2012)
  • Discovery of an unexpected role of the EGF receptor in controlling basolateral to apical transport of vesicles. Key to this work was a novel cascade of kinases leading to the vesicle transport protein Rab11FIP5 (Nat Cell Biol 2012)
  • The elucidation of how multiple trafficking GTPases can function with the same effector (Myosin-5B) to control the function of the apical membrane and lumen (PNAS 2011)

Key Recent Publications

Bryant DM, Roignot J, Datta A, Overeem AW, Kim M, Yu W, Peng X, Eastburn DJ, Ewald AJ, Werb Z, Mostov KE. A molecular switch for the orientation of epithelial cell polarization. Dev Cell, Epub 9 Oct 2014 DOI: http://dx.doi.org/10.1016/j.devcel.2014.08.027

Tran CS, Eran Y, Ruch TR, Bryant DM, Datta A, Brakeman P, Kierbel A, Wittmann T, Metzger RJ, Mostov KE, Engel JN. Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection. Cell Host Microbe 15: 636-43, 2014

Lepanto P, Bryant DM, Rossello J, Datta A, Mostov KE, Kierbel A. Pseudomonas aeruginosa interacts with epithelial cells rapidly forming aggregates that are internalized by a Lyn-dependent mechanism. Cell Micro 13: 1212-22, 2011

Roland, JT*, Bryant, DM*, Datta, A, Itzen, A, Mostov, KE, Goldenring, JR. Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. PNAS 108: 2789-94, 2011

Su T, Bryant DM, Luton F, Vergés M, Ulrich SM, Hansen KC, Datta A, Eastburn DJ, Burlingame AL, Shokat KM, Mostov KE. A kinase cascade leading to Rab11-FIP5 controls transcytosis of the polymeric immunoglobulin receptor. Nat Cell Biol 12: 1143-53, 2010

Bryant DM, Datta A, Rodríguez-Fraticelli AE, Peränen J, Martín-Belmonte F, Mostov KE. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol 12: 1035-45, 2010

Biography

Education and qualifications

2006: PhD, University of Queensland, Australia, Supervisor Jennifer Stow
2002: BSc (Hons) Class I, University of Queensland, Australia

Appointments

2014-present: Senior Lecturer/Beatson Associate, University of Glasgow
2012-2014: Associate Academic Researcher, University of California, San Francisco, USA
2006-2012: Postdoctoral Fellow with Keith Mostov, UC San Francisco, USA

Recent Publications

2017

Gao L, Yang Z, Hiremath C, Zimmerman SE, Long B, Brakeman PR, Mostov KE, Bryant DM, Luby-Phelps K, Marciano DK (2017) Developing renal tubules orient cell division via Afadin to position the tubule lumen. Development, in press

Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Román-Fernández Á, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM, Salmeron-Sanchez M, Machesky LM, Carlin LM, Blyth K, Mazzone M, Zanivan S.Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J EMBO J 36: 2373-89, 2017

Ruch TR, Bryant DM, Mostov KE, Engel JN. Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity. Mol Biol Cell 28: 252-60, 2017

2016

Yang Z, Zimmerman SE, Tsunezumi J, Braitsch C, Trent C, Bryant DM, Cleaver O, Gonzalez-Manchon C, Marciano DK. Role of CD34 family members in lumen formation in the developing kidney. Dev Biol 418: 66-74, 2016

Bryant DM, Yap AS. Editorial overview: Membrane traffic and cell polarity. Traffic 17: 1231-2, 2016

Roman-Fernandez A, Bryant DM. Complex polarity: Building multicellular tissues through apical membrane traffic. Traffic 17: 1244-61, 2016

2015

Overeem AW, Bryant DM, van ISC. Mechanisms of apical-basal axis orientation and epithelial lumen positioning. Trends Cell Biol 2015. Epub 2015/05/06

2014

Bryant DM, Roignot J, Datta A, Overeem AW, Kim M, Yu W, Peng X, Eastburn DJ, Ewald AJ, Werb Z, Mostov KE. A molecular switch for the orientation of epithelial cell polarization. Dev Cell 31: 171-87, 2014

Tran CS, Eran Y, Ruch TR, Bryant DM, Datta A, Brakeman P, Kierbel A, Wittmann T, Metzger RJ, Mostov KE, Engel JN. Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection. Cell Host Microbe 15: 636-43, 2014

2012

Apodaca G, Gallo LI, Bryant DM. Role of membrane traffic in the generation of epithelial cell asymmetry. Nat Cell Biol 14: 1235-43, 2012

Gálvez-Santisteban M*, Rodriguez-Fraticelli AE*, Bryant DM, Vergarajauregui S, Yasuda T, Bañón-Rodríguez I, Bernascone I, Datta A, Spivak N, Young K, Slim CL, Brakeman PR, Fukuda M, Mostov KE, Martín-Belmonte F. Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells. Nat Cell Biol 14: 838-49, 2012

Lab Members

bryant group

Post-docs

Mohammed Mansour
Alvaro Roman Fernandez

Scientific Officer

Emma Sandilands

PhD Student

Marisa Nacke

Research

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Seminars

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