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Dr Gillian Fraser

Dr Gillian Fraser

Head of the Division of Microbiology & Parasitology

Senior University Lecturer in Cellular and Molecular Microbiology

Niccoli Fellow in the Natural Sciences, Queens' College

Bacterial motility & flagella biogenesis; Bacterial nucleoid structure, dynamics & gene expression

Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge
CB2 1QP

Office Phone: +44 (0)1223 330245 (Pathology) +44 (0)1223 330179 (Queens')

Biography:

Gillian Fraser graduated from the University of Glasgow with a BSc (First Class) in Microbiology. After completing her PhD studies in the Department of Pathology at Cambridge, she was awarded a Wellcome Trust International Prize Travelling Research Fellowship to work on bacterial flagella biogenesis in the laboratories of Robert Macnab (Yale) and Colin Hughes (Cambridge). Gillian still works on flagella and has also started a new project on the structure of the bacterial nucleoid. She is a Fellow of the Royal Society of Biology.

At Queens' College, Gillian is Director of Studies (Biological Natural Sciences), Deputy Dean of College and Niccoli Fellow in the Natural Sciences. The Niccoli Fellowship was endowed in 2015 by Dr Demis Hassabis and Dr Teresa Niccoli. Dr Niccoli graduated from Queens' in 1997 with a B.A. in Natural Sciences (Pathology).

Research themes

Molecular, Structural & Cellular Microbiology:

Bacterial motility & flagella biogenesis; Bacterial nucleoid structure, dynamics & gene expression

Research Interests

Bacterial motility & flagella biogenesis

Pathogenic bacteria are often motile and their ability to swim through liquids and swarm over surfaces facilitates pathogen-host interactions and colonization of nutrient–rich environments. Many bacteria build complex rotary nanomotors, called flagella, which drive swimming and swarming motility. A remarkable feature of flagella is that they are essentially self-assembling. Thousands of flagellar structural subunits are exported across the cell membrane by dedicated type III export machinery located at the base of each flagellum. Subunits then transit through a narrow channel at the core of the nascent flagellum to reach the assembly site at the tip of the structure, up to 20 μm away from the cell surface. Our work aims to uncover the molecular mechanisms underpinning flagellum assembly, focusing on the interactions between flagellar structural proteins and components of the membrane export machinery. Funded by a BBSRC project grant (to Gillian Fraser and co-investigator Colin Hughes)

A chain mechanism for bacterial flagellum growth (see Nature 504:287-290). Flagella on the surface of the bacterial cell (inset top right, Salmonella cell membrane stained green and flagella stained red) comprise three contiguous substructures - the basal body, hook and filament - that are assembled sequentially. A central channel runs through these substructures to the flagellum tip.The basal body houses the flagellar export machinery (A) and the rod, which extends from the inner membrane (IM) and crosses the periplasm, peptidoglycan (PG) cell wall and outer membrane (OM). The cell surface hook is a flexible universal joint that connects the external flagellum filament to the basal body.  

Flagella on the surface of the bacterial cell (inset top right, Salmonella cell membrane stained green and flagella stained red, visualized by epifluorescence microscopy) comprise three contiguous substructures - the basal body, hook and filament - that are assembled sequentially. A central channel runs through these substructures to the flagellum tip. The basal body houses the flagellar export machinery (A) and the rod (FliE, FlgB, FlgC, FlgF and FlgG), which extends from the inner membrane (IM) and crosses the periplasm, peptidoglycan (PG) cell wall and outer membrane (OM). The cell surface hook (FlgE) is a flexible universal joint that connects the external flagellum filament (flagellin, FliC) to the basal body. (A) Subunits of the rod, hook and filament link head-to-tail at the cytoplasmic membrane export machinery. Subunits are first unfolded by the export ATPase complex (red) and then dock at the FlhB export gate (orange). The N-terminal helix of the docked subunit is then captured by the free C-terminal helix of an exiting subunit in the flagellum channel. (B) Sequential subunits are linked head-to-tail in a chain by juxtaposed terminal helices forming parallel coiled-coils. The resulting chain of unfolded subunits is connected through the flagellum central channel to the distal tip of the flagellum. (C) The subunits in the chain transit from the gate to the tip. Subunits fold and incorporate into the flagellum tip beneath cap foldases (FlgJ for rod, FlgD for hook and FliD for filament subunit assembly). Subunit folding and/or crystallization not only provides a strong anchor at the flagellum tip, it also shortens the chain in the channel thus exerting a pulling force on the next subunit at the export gate, pulling it from the gate. The pulling force then drops rapidly as the new unfolded subunit enters the channel. This process repeats for each subunit captured into the chain.(A) Subunits of the rod, hook and filament link head-to-tail at the cytoplasmic membrane export machinery. Subunits are first unfolded by the export ATPase complex (red). Rod and hook subunits then dock at the FlhB export gate (orange). The N-terminal helix of the docked subunit is then captured by the free C-terminal helix of an exiting subunit in the flagellum channel. (B) Sequential subunits are linked head-to-tail in a chain by juxtaposed terminal helices forming parallel coiled-coils. The resulting chain of unfolded subunits is connected through the flagellum central channel to the distal tip of the growing structure. (C) The subunits in the chain transit from the gate to the tip. Subunits fold and incorporate into the flagellum tip beneath cap foldases. Subunit folding and/or crystallization not only provides a strong anchor at the flagellum tip, it also shortens the subunit chain in the channel thus exerting a pulling force on the next subunit at the export gate, pulling it from the gate. The pulling force then drops rapidly as the new unfolded subunit enters the channel. This process repeats for each subunit captured into the chain.

 

Bacterial nucleoid structure, dynamics & gene expression

The bacterial nucleoid is a large dynamic structure containing DNA, RNA and proteins. To fit into the cell the nucleoid must be compacted extensively, and must fold in ways that allow genetic information to be replicated and transcribed. This is especially important in bacteria as their survival depends on their ability to adapt rapidly to the external environment by modulating gene expression and growth rate. We aim to understand how the nucleoid folds and how this folding influences transcription. Nucleoid folding is orchestrated, in part, by specialized DNA-binding proteins called nucleoid associated proteins (NAPs). We have mapped the genomic binding sites of several NAPs - including Fis, HNS, IHF and HU - in the model bacterium E. coli K12. We have also determined the effects of NAP binding on both gene expression and genome-wide binding of RNA polymerase. We are now building on this work to study how NAPs influence long-range DNA interactions and the 3D structure of the nucleoid. In collaboration with Pietro Cicuta, Department of Physics.                                                                                                        

Key Publications

  • Evans LDB, Hughes C and Fraser GM.  (2014) Building a flagellum outside the bacterial cell. Trends in Microbiology 22: 566-572
  • Evans LDB, Poulter S, Terentjev EM, Hughes C and Fraser GM. (2013)  A chain mechanism for flagellum growth. Nature 504:287-290
  • Kahramanoglou CSeshasayee ASN, Prieto A, Ibberson D, Schmidt S, Zimmerman J, Benes V, Fraser GM* and Luscombe NM* (2011) Direct and indirect effects of H-NS and Fis on global gene expression control in E. coli. Nucleic Acids Research 39:2073-91.
  • Green JCD, Kahramanoglou C, Rahman A, Pender A, Charbonnel N, and Fraser GM (2009) Recruitment of the earliest component of the bacterial flagellum to the old cell division pole by a membrane-associated flagellar signal recognition particle-family GTPase.  Journal of Molecular Biology 391:679-90.
  • Evans LDB, Stafford GP, Ahmed S, Fraser GM, and Hughes C (2006) An escort mechanism for cycling of export chaperones during flagellum assembly.  Proceedings of the National Academy of Sciences USA 103: 17474-17479

Gillian Fraser’s full publications list on Google Scholar