Profile

Career

2007 -	Lecturer	Department of Biology, University of York
2006 - 2007	MRC New Investigator	Department of Biology, University of York
2004 - 2005	MRC New Investigator	Faculty of Life Sciences, University of Manchester
2000 - 2004	Research Associate	Biomolecular Sciences, UMIST
1998 - 2000	Research Associate	William Dunn School of Pathology, University of Oxford
1995	PhD	University of Pavia, Italy
1995 - 1997	Research Associate	Biochemistry, University of Oxford
1993 - 1994	Visiting Scientist	University of California, Berkeley, CA
1991	MSc	University of Pavia, Italy

Research

Overview

Research interests focus on the molecular mechanisms and dynamics of procaryotic DNA segregation. Multidrug resistance plasmids harbour their own survival system, a partition cassette, which ensures an accurate and equitable segregation of the plasmids from one generation to the next at cell division. When this system malfunctions, the plasmid is not stably inherited and is ultimately lost. The multidrug resistance plasmid TP228 replicates at low copy number in Escherichia coli. The partition cassette (~1,100 bp) of TP228 consists of the parFG genes and upstream noncoding sequence ( parH ) which harbours a series of related direct and invert repeat motifs. We have recently shown that ParF is an ATPase that assembles into extensive, multistranded filaments in vitro. The partner partition protein ParG plays at least two distinct roles in ParF polymerization dynamics: 1) it enhances ParF ATPase activity and 2) it promotes filament bundling. The recently acquired data allowed us to propose a mitotic spindle-like molecular mechanism for plasmid segregation in E. coli. Investigations are also underway to study the molecular mechanisms of genome segregation in the archaeon Sulfolobus.

Discoveries

The finding that the ATPase activity of ParF is stimulated by the partition protein ParG via an arginine finger-like mechanism analogous to that of eukaryotic RasGAPs.

Current projects

• Novel molecular targets to combat antibiotic resistance: probing the assembly dynamics of a bacterial mitotic spindle (Funding body: MRC)
• Probing DNA segregation in archaea: molecular dissection of an atypical tricistronic partition system from Sulfolobus (Funding body: BBSRC)
  

Research group(s)

Status	Name	Project
Post doctoral research associate	Dr Fernando Rodriguez-Castaneda	Molecular mechanisms and dynamics of DNA segregation in the archaeon Sulfolobus
Post doctoral research associate	Dr Brett McLeod	Novel molecular targets to combat antibiotic resistance: probing the assembly dynamics of a bacterial mitotic spindle
Research Technician	Madhuri Barge	Structure-function analysis of the partition protein ParG
Research Technician	Anne Kalliomaa Sanford	Transcription factors and DNA segregation factors of the archaeon Sulfolobus

    

Available PhD research projects

Targeting a bacterial mitotic spindle to combat antibiotic resistance (for 2012-13)

Bacterial multidrug resistance is a global burden on human health worldwide. Large, low copy number plasmids, implicated in antibiotic resistance, have evolved sophisticated strategies to ensure their faithful distribution at cell division. Multidrug resistance plasmids harbour their own survival system, a partition cassette, which ensures an accurate and equitable segregation of the plasmids from one generation to the next at cell division. When this system malfunctions, the plasmid is not stably inherited and is ultimately lost. The multidrug resistance plasmid TP228 replicates at low copy number in Escherichia coli. The partition cassette (~1,100 bp) of TP228 consists of the parFG genes and upstream noncoding sequence (parH) which harbours a series of related direct and invert repeat motifs. We have shown that ParF is an ATPase that assembles into extensive, multistranded filaments in vitro. The partner partition protein ParG plays at least two distinct roles in ParF polymerization dynamics: 1) it enhances ParF ATPase activity and 2) it promotes filament bundling. The recently acquired data allowed us to propose a mitotic spindle-like molecular mechanism for plasmid segregation in E. coli. This project will investigate the molecular mechanism of ParF polymerization and how ParF polymers drive DNA segregation at cell division. The study will involve molecular biology, biochemical and biophysical approaches in parallel with fluorescence microscopy to visualize DNA positioning, trafficking and segregation in the cell.

Publications

Selected publications

•  Hayes F, Barillà D (2010) Extrachromosomal components of the nucleoid: recent developments in deciphering the molecular basis of plasmid segregation. In CJ Dorman and RT Dame (ed.), Bacterial Chromatin, Springer, The Netherlands, pp. 49-70.
• Zampini M, Derome A, Bailey SES, Barillà D, Hayes F (2009) Recruitment of the ParG segregation protein to different affinity DNA sites. J Bacteriol 191: 3832-3841.
• Derome A, Hoischen C, Bussiek M, Grady R, Adamczyk M, Kedzierska B, Diekmann S, Barillà D, Hayes F (2008) Centromere anatomy in the multidrug resistant pathogen Enterococcus faecium. Proc Natl Acad Sci USA 105: 2151-2156.
• Barillà D, Carmelo E, Hayes F (2007) The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif. Proc Natl Acad Sci USA 104: 1811 -1816.
• Barillà D, Rosenberg MF, Nobbmann U, Hayes F (2005) Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF. EMBO J 24: 1453-1464.

External activities

Memberships

• Member of the Society for General Microbiology (SGM)
• Member of the Biochemical Society