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Dr Vicki Gold

Dr Vicki Gold

Senior Lecturer

 7454

 +44 (0)1392 727454

 Living Systems Institute T04.16

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD

Overview

Electron cryo-tomography of protein transport systems

We employ different techniques in electron cryo-microscopy to study the fundamental process of protein transport across cell membranes. We investigate a number of research themes - the bacterial type IV pilus assembly machinery, mitochondrial protein import and the mechanism of filamentous bacteriophage infection and egress. These are important topics that can help us to understand the principles of protein transport, and how mechanisms may be compromised in disease states or exploited on bacterial and viral infection.

 

Biography

During her undergraduate summer project, Vicki Gold became fascinated by the concept of protein translocation across membranes. She embarked on a career starting at the University of Bristol, where she was awarded her PhD for studies on the general protein secretory (Sec) pathway in bacteria. After award of an EMBO Long-Term fellowship, she moved to the Max-Planck Institute of Biophysics in Frankfurt, Germany to work on mitochondrial protein import. During this time, the technique of electron cryo-microscopy was undergoing a so-called “resolution revolution”. The ability to determine protein structures at near-atomic level detail sparked her interest in the powerful method. Vicki developed her own research themes using electron cryo-microscopy to investigate protein transport systems and returned to the UK in 2017 as a Senior Lecturer and PI. Vicki is based in the Living Systems Institute.

 

Research Team

Dr. Alexander Neuhaus (PDRA) – the bacterial type IV pilus machinery

Dr. Rebecca Conners (PDRA) – the mechanism of filamentous phage infection and egress

Dr. Mathew McLaren (electron microscopy Experimental Officer)

Dr. Kelly Sanders (wet laboratory technician)

Emma Buzzard – (SWBio DTP student) - Investigating mitochondrial complex I assembly as a factor for disease

Qualifications

2008: PhD Biochemistry, University of Bristol
2004: BSc Biological Sciences, University of Warwick

Career

2016-present: Senior Lecturer, Living Systems Institute, University of Exeter, UK
2011-2016: Postdoctoral Fellow, Department of Structural Biology, Max Planck Institute of Biophysics, Germany
2008-2011: Postdoctoral Research Associate, School of Biochemistry, University of Bristol, UK    
2004-2007: Postgraduate Research Assistant, School of Biochemistry, University of Bristol, UK     

Fig. 1 To locate the mitochondrial import machinery, a pre-protein can be arrested across both mitochondrial membranes and labelled with a dense quantum-dot tag (black spheres). This reveals import site distribution on the outer membrane (green) and with respect to the cristae (yellow) and crista junctions (red box; yellow arrowheads). Blue box; a close up of the import machinery in action with protein densities marked with blue and green arrowheads and the dense label in black. OM, outer membrane; IM, inner membrane.

Fig. 2.Slices through tomograms and corresponding structures determined by sub-tomogram averaging highlight the type IV pilus machinery (boxed) in the closed (blue, pilus retracted) and open (green, pilus assembled) states.

Research

Research interests

The bacterial type IV pilus assembly machinery

Type IV pili are several micron long filaments that power bacterial motility and adhesion. Pili thus enable bacteria to move within and interact with our environment, and are key determinants of virulence. The machinery that assembles type IV pili is a massive multi-membrane spanning complex, which in some species has a dual function in DNA uptake. This ability enables rapid genetic adaptation and the development of resistance to antimicrobials. We are using electron cryo-microscopy to study pili and the machinery that assembles them at high-resolution detail. For further detail see Gold, V. et al, eLife (2015) & Gold, V. & Kudrayashev, M., Curr Opin Struct Biol (2016) and Daum, B. et al, Biol Chem (2018).

 

Mitochondrial protein import

Mitochondria are the primary cellular source of ATP and form an important bioenergetic and metabolic signalling hub. Only 1% of mitochondrial proteins are encoded on mitochondrial DNA and the remainder are imported from the cytosol. Protein translocases are therefore essential for correct protein targeting and localisation, and a growing number of human pathologies have been linked to mitochondria and the import apparatus. We work to understand how protein import into mitochondria works by electron cryo-tomography, single-particle analysis and protein biochemistry. For further detail see Gold, V. et al, Nat Commun (2014), Gold, V. et al, EMBO Rep (2017)Gold, V. et al, Methods Mol Biol (2017).

 

Filamentous phage infection and egress

In a world becoming increasingly dominated by antibiotic resistant bacteria, treatment strategies need to be reassessed. We are using electron cryo-microscopy to study the filamentous phage (Ff) encoded assembly system, with the ultimate aim of developing cell-targeted antimicrobials. We are working to reveal structural details of the virus-host interaction, and of the machinery that enables the virus to exit the cell and proliferate.

 

Equipment and facilities

We are currently equipped with brand new state-of-the-art laboratories for cryoEM sample preparation, imaging and data processing. We employ a cryo- and automation-capable 120kV microscope (FEI Tecnai Spirit) with CMOS camera for screening samples and generation of initial single particle EM and cryoET data sets. For higher resolution data collection we use our shared GW4 200kV cryo-microscope (FEI Talos Arctica) fitted with a K2 direct electron detector at the South West Regional Facility for CryoEM. We are also well equipped with standard wet laboratory equipment for molecular biology, biochemistry, protein expression and purification. 

 

Research networks

  • Prof. Agnieszka Chacinska, IIMCB Warsaw, Poland
  • Prof. Ian Collinson, University of Bristol, UK
  • Prof. Beate Averhoff, University of Frankfurt, Germany
  • GW4 South West Regional Facility for CryoEM

Research grants

  • 2019 Wellcome Trust
    Microbes produce long, hair-like appendages called flagella and pili, which project from their cell surface. Both types of filament are multifunctional and act as a means of communication between individual microbes, and between microbes and the environment. Flagella and pili also enable microbes to swim, attach to and “walk” along surfaces, exchange genetic material and form biofilms. Examples include dental plaque or dangerous contamination on hospital catheters and implants. As these filaments also enable microbes to move, they help microbes to spread and infect the human body. Study of the dynamic behaviour of these filaments will help us understand their function and inform the design of new drugs. This is especially important in view of the growing number of infectious bacteria that develop antibiotic resistance. Through recent work we have determined the structures of flagella and pili at very high detail, where their atomic composition can be seen. In this project, we will now explore how these atomic structures determine large-scale motion. This will provide targets for the development of new drugs, which can disrupt the motion and spread of infectious microbes.
  • 2018 BBSRC
    The bacterial type IV pilus machinery as a DNA translocator
  • 2018 Wellcome Trust
    The filamentous phage assembly system as a therapeutic tool
  • 2017 Wellcome Trust
    Electron Cryo-microscopy equipment grant

Publications

Key publications | Publications by category | Publications by year

Key publications


Gold VAM, Brandt T, Cavellini L, Cohen MM, Ieva R, van der Laan M (2017). Analysis of mitochondrial membrane protein complexes by electron cryo-tomography. In  (Ed) Methods in Molecular Biology, 315-336.  Abstract.
Gold VA, Chroscicki P, Bragoszewski P, Chacinska A (2017). Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography. EMBO Rep, 18(10), 1786-1800. Abstract.  Author URL.  Full text.
Gold VAM, Salzer R, Averhoff B, Kühlbrandt W (2015). Structure of a type IV pilus machinery in the open and closed state. Elife, 4 Abstract.  Author URL.  Full text.
Gold VAM, Ieva R, Walter A, Pfanner N, van der Laan M, Kühlbrandt W (2014). Visualizing active membrane protein complexes by electron cryotomography. Nat Commun, 5 Abstract.  Author URL.  Full text.
Gold VAM, Whitehouse S, Robson A, Collinson I (2013). The dynamic action of SecA during the initiation of protein translocation. BIOCHEMICAL JOURNAL, 449, 695-705. Author URL.
Gold VAM, Robson A, Bao H, Romantsov T, Duong F, Collinson I (2010). The action of cardiolipin on the bacterial translocon. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(22), 10044-10049. Author URL.

Publications by category


Journal articles

Alvira S, Watkins DW, Troman L, Lorriman J, Daum B, Gold VAM, Collinson I (In Press). Trans-membrane association of the Sec and BAM complexes for bacterial outer-membrane biogenesis.  Abstract.
Wang S, Powers R, Gold VAM, Rapoport T (2018). The ER morphology-regulating lunapark protein induces the formation of stacked bilayer discs. Life Science Alliance Full text.
Daum B, Gold V (2018). Twitch or swim: towards the understanding of prokaryotic motion based on the type IV pilus blueprint. Biol Chem, 399(7), 799-808. Abstract.  Author URL.  Full text.
Gold VA, Chroscicki P, Bragoszewski P, Chacinska A (2017). Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography. EMBO Rep, 18(10), 1786-1800. Abstract.  Author URL.  Full text.
Turakhiya U, von der Malsburg K, Gold VAM, Guiard B, Chacinska A, van der Laan M, Ieva R (2016). Protein Import by the Mitochondrial Presequence Translocase in the Absence of a Membrane Potential. J Mol Biol, 428(6), 1041-1052. Abstract.  Author URL.
Gold V, Kudryashev M (2016). Recent progress in structure and dynamics of dual-membrane-spanning bacterial nanomachines. Curr Opin Struct Biol, 39, 1-7. Abstract.  Author URL.
Salzer R, D'Imprima E, Gold VAM, Rose I, Drechsler M, Vonck J, Averhoff B (2016). Topology and Structure/Function Correlation of Ring- and Gate-forming Domains in the Dynamic Secretin Complex of Thermus thermophilus. J Biol Chem, 291(28), 14448-14456. Abstract.  Author URL.  Full text.
Gold VAM, Salzer R, Averhoff B, Kühlbrandt W (2015). Structure of a type IV pilus machinery in the open and closed state. Elife, 4 Abstract.  Author URL.  Full text.
Stockburger C, Gold VAM, Pallas T, Kolesova N, Miano D, Leuner K, Müller WE (2014). A cell model for the initial phase of sporadic Alzheimer's disease. J Alzheimers Dis, 42(2), 395-411. Abstract.  Author URL.
Schulze RJ, Komar J, Botte M, Allen WJ, Whitehouse S, Gold VAM, Nijeholtb JALA, Huard K, Berger I, Schaffitzel C, et al (2014). Membrane protein insertion and proton-motive-force-dependent secretion through the bacterial holo-translocon SecYEG-SecDF-YajC-YidC. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(13), 4844-4849. Author URL.
Davies KM, Daum B, Gold VAM, Mühleip AW, Brandt T, Blum TB, Mills DJ, Kühlbrandt W (2014). Visualization of ATP synthase dimers in mitochondria by electron cryo-tomography. J Vis Exp(91). Abstract.  Author URL.  Full text.
Gold VAM, Ieva R, Walter A, Pfanner N, van der Laan M, Kühlbrandt W (2014). Visualizing active membrane protein complexes by electron cryotomography. Nat Commun, 5 Abstract.  Author URL.  Full text.
Gold VAM, Whitehouse S, Robson A, Collinson I (2013). The dynamic action of SecA during the initiation of protein translocation. BIOCHEMICAL JOURNAL, 449, 695-705. Author URL.
Whitehouse S, Gold VAM, Robson A, Allen WJ, Sessions RB, Collinson I (2012). Mobility of the SecA 2-helix-finger is not essential for polypeptide translocation via the SecYEG complex. JOURNAL OF CELL BIOLOGY, 199(6), 919-929. Author URL.
Hizlan D, Robson A, Whitehouse S, Gold VA, Vonck J, Mills D, Kühlbrandt W, Collinson I (2012). Structure of the SecY complex unlocked by a preprotein mimic. Cell Rep, 1(1), 21-28. Abstract.  Author URL.
Deville K, Gold VAM, Robson A, Whitehouse S, Sessions RB, Baldwin SA, Radford SE, Collinson I (2011). The Oligomeric State and Arrangement of the Active Bacterial Translocon. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(6), 4659-4669. Author URL.
Gold VAM, Robson A, Bao H, Romantsov T, Duong F, Collinson I (2010). The action of cardiolipin on the bacterial translocon. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(22), 10044-10049. Author URL.
Robson A, Gold VAM, Hodson S, Clarke AR, Collinson I (2009). Energy transduction in protein transport and the ATP hydrolytic cycle of SecA. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(13), 5111-5116. Author URL.
Robson A, Booth AEG, Gold VAM, Clarke AR, Collinson I (2007). A large conformational change couples the ATP binding site of SecA to the SecY protein channel. JOURNAL OF MOLECULAR BIOLOGY, 374(4), 965-976. Author URL.
Gold VAM, Robson A, Clarke AR, Collinson I (2007). Allosteric regulation of SecA - Magnesium-mediated control of conformation and activity. JOURNAL OF BIOLOGICAL CHEMISTRY, 282(24), 17424-17432. Author URL.
Gold VAM, Duong F, Collinson I (2007). Structure and function of the bacterial Sec translocon. MOLECULAR MEMBRANE BIOLOGY, 24(5-6), 387-394. Author URL.

Chapters

Gold VAM, Brandt T, Cavellini L, Cohen MM, Ieva R, van der Laan M (2017). Analysis of mitochondrial membrane protein complexes by electron cryo-tomography. In  (Ed) Methods in Molecular Biology, 315-336.  Abstract.

Publications by year


In Press

Alvira S, Watkins DW, Troman L, Lorriman J, Daum B, Gold VAM, Collinson I (In Press). Trans-membrane association of the Sec and BAM complexes for bacterial outer-membrane biogenesis.  Abstract.

2018

Wang S, Powers R, Gold VAM, Rapoport T (2018). The ER morphology-regulating lunapark protein induces the formation of stacked bilayer discs. Life Science Alliance Full text.
Daum B, Gold V (2018). Twitch or swim: towards the understanding of prokaryotic motion based on the type IV pilus blueprint. Biol Chem, 399(7), 799-808. Abstract.  Author URL.  Full text.

2017

Gold VAM, Brandt T, Cavellini L, Cohen MM, Ieva R, van der Laan M (2017). Analysis of mitochondrial membrane protein complexes by electron cryo-tomography. In  (Ed) Methods in Molecular Biology, 315-336.  Abstract.
Gold VA, Chroscicki P, Bragoszewski P, Chacinska A (2017). Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography. EMBO Rep, 18(10), 1786-1800. Abstract.  Author URL.  Full text.

2016

Turakhiya U, von der Malsburg K, Gold VAM, Guiard B, Chacinska A, van der Laan M, Ieva R (2016). Protein Import by the Mitochondrial Presequence Translocase in the Absence of a Membrane Potential. J Mol Biol, 428(6), 1041-1052. Abstract.  Author URL.
Gold V, Kudryashev M (2016). Recent progress in structure and dynamics of dual-membrane-spanning bacterial nanomachines. Curr Opin Struct Biol, 39, 1-7. Abstract.  Author URL.
Salzer R, D'Imprima E, Gold VAM, Rose I, Drechsler M, Vonck J, Averhoff B (2016). Topology and Structure/Function Correlation of Ring- and Gate-forming Domains in the Dynamic Secretin Complex of Thermus thermophilus. J Biol Chem, 291(28), 14448-14456. Abstract.  Author URL.  Full text.

2015

Gold VAM, Salzer R, Averhoff B, Kühlbrandt W (2015). Structure of a type IV pilus machinery in the open and closed state. Elife, 4 Abstract.  Author URL.  Full text.

2014

Stockburger C, Gold VAM, Pallas T, Kolesova N, Miano D, Leuner K, Müller WE (2014). A cell model for the initial phase of sporadic Alzheimer's disease. J Alzheimers Dis, 42(2), 395-411. Abstract.  Author URL.
Schulze RJ, Komar J, Botte M, Allen WJ, Whitehouse S, Gold VAM, Nijeholtb JALA, Huard K, Berger I, Schaffitzel C, et al (2014). Membrane protein insertion and proton-motive-force-dependent secretion through the bacterial holo-translocon SecYEG-SecDF-YajC-YidC. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(13), 4844-4849. Author URL.
Davies KM, Daum B, Gold VAM, Mühleip AW, Brandt T, Blum TB, Mills DJ, Kühlbrandt W (2014). Visualization of ATP synthase dimers in mitochondria by electron cryo-tomography. J Vis Exp(91). Abstract.  Author URL.  Full text.
Gold VAM, Ieva R, Walter A, Pfanner N, van der Laan M, Kühlbrandt W (2014). Visualizing active membrane protein complexes by electron cryotomography. Nat Commun, 5 Abstract.  Author URL.  Full text.

2013

Gold VAM, Whitehouse S, Robson A, Collinson I (2013). The dynamic action of SecA during the initiation of protein translocation. BIOCHEMICAL JOURNAL, 449, 695-705. Author URL.

2012

Whitehouse S, Gold VAM, Robson A, Allen WJ, Sessions RB, Collinson I (2012). Mobility of the SecA 2-helix-finger is not essential for polypeptide translocation via the SecYEG complex. JOURNAL OF CELL BIOLOGY, 199(6), 919-929. Author URL.
Hizlan D, Robson A, Whitehouse S, Gold VA, Vonck J, Mills D, Kühlbrandt W, Collinson I (2012). Structure of the SecY complex unlocked by a preprotein mimic. Cell Rep, 1(1), 21-28. Abstract.  Author URL.

2011

Deville K, Gold VAM, Robson A, Whitehouse S, Sessions RB, Baldwin SA, Radford SE, Collinson I (2011). The Oligomeric State and Arrangement of the Active Bacterial Translocon. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(6), 4659-4669. Author URL.

2010

Gold VAM, Robson A, Bao H, Romantsov T, Duong F, Collinson I (2010). The action of cardiolipin on the bacterial translocon. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(22), 10044-10049. Author URL.

2009

Robson A, Gold VAM, Hodson S, Clarke AR, Collinson I (2009). Energy transduction in protein transport and the ATP hydrolytic cycle of SecA. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(13), 5111-5116. Author URL.

2007

Robson A, Booth AEG, Gold VAM, Clarke AR, Collinson I (2007). A large conformational change couples the ATP binding site of SecA to the SecY protein channel. JOURNAL OF MOLECULAR BIOLOGY, 374(4), 965-976. Author URL.
Gold VAM, Robson A, Clarke AR, Collinson I (2007). Allosteric regulation of SecA - Magnesium-mediated control of conformation and activity. JOURNAL OF BIOLOGICAL CHEMISTRY, 282(24), 17424-17432. Author URL.
Gold VAM, Duong F, Collinson I (2007). Structure and function of the bacterial Sec translocon. MOLECULAR MEMBRANE BIOLOGY, 24(5-6), 387-394. Author URL.

Vicki_Gold Details from cache as at 2019-10-16 04:43:43

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External Engagement and Impact

Administrative responsibilities

Chair of the Steering committee for the South West Regional Facility for CryoEM, GW4 and University of Exeter                  

 


Awards

EMBO Long-Term Fellowship, held at the Max-Planck Institute of Biophysics, Frankfurt am Main, Germany (2011-2013)

Lead PI on eBic BAG (Block Allocation Group) for time at the  Electron Bio-Imaging Centre (eBIC) at Diamond

Teaching

Supervision / Group

Postdoctoral researchers

  • Becky Conners
  • Alexander Neuhaus

Postgraduate researchers

  • Emma Buzzard

Research Technicians

  • Mathew McLaren
  • Kelly Sanders

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