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Dr Monika Bokori-Brown

Dr Monika Bokori-Brown

Research Fellow

 +44(0)1392 72 5177

 Geoffrey Pope 

 

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK

Overview

Broad research specialisms:

  • Molecular cell biology
  • Bacterial protein toxins
  • Membrane biophysics
  • Microbial pathogenesis

Qualifications

2001-2005 PhD Molecular-Cell Biology, University of Cambridge, UK
1997-1998 MSc Molecular Biology, University of Portsmouth, UK
1991-1997 BSc/BA Biology/English, University of Pécs, Hungary

Career

2013-date: Research Fellow, Physics and Astronomy, CEMPS, University of Exeter, UK

2007-2013: Research Fellow, Biosciences, CLES, University of Exeter, UK

2006-2007: Postdoctoral Molecular Biologist, Population Genetics Technologies Ltd., Cambridge, UK

2005-2005: Postdoctoral Research Scientist, MRC Mitochondrial Biology Unit, Cambridge, UK

2000-2001: Scientist-Molecular Biology, Centre for Applied Microbiology and Research, Porton Down, UK

1999-2000: Scientist, Lab Staff; Client Company: Centre for Applied Microbiology and Research, Porton Down, UK

Research group links

Research

Research interests

I am a molecular cell biologist by training but over the past four years my research has developed at the interface between physics and biology. This has enabled me to develop a unique set of skills required for a multi-disciplinary research career and coincided with first author publications in high impact journals, such as Nature Communications and the Journal of Biological Chemistry. Therefore, I have proven ability to carry out outstanding quality research in an inter-disciplinary setting.

My main research interest is to understand the molecular, cellular and biophysical aspects of protein-membrane interactions with a focus on membrane-active pore forming toxins (PFTs) produced by bacterial pathogens. My future research aims to address fundamental questions about the biophysical mechanism by which the host tissue is invaded by bacterial pathogens, an area of research that could have significant longer term implications for the prevention and treatment of bacterial infections.

I graduated in Biology and English from the University of Pécs, Hungary in 1997 and continued my career development in the UK. In 1998 I received my MSc in Molecular Biology (distinction awarded) from the University of Portsmouth. In 1999 I was recruited to the Centre for Applied Microbiology and Research (CAMR; now Public Health England), Porton Down, UK as a Scientist-Molecular Biology to be part of the molecular team of a commercial-oriented, multi-disciplinary project. This entailed the design and development of novel recombinant proteins derived from Clostridium botulinum neurotoxin for the treatment of chronic pain using innovative biochemical and molecular biology techniques, which today forms one of the technological platforms of the global pharmaceutical company, Ipsen. During my employment at CAMR I also participated in the construction of a transconjugant vector for use in Clostridium difficile to gain a greater understanding of its pathogenesis in order to identify novel vaccine candidates (Purdy, D., et al., Mol Microbiol 2002). 

To further my career in human disease-related research, in 2001 I joined the Mitochondrial Diseases research group of Prof Ian Holt at the MRC Mitochondrial Biology Unit, University of Cambridge as a MRC-funded PhD student where my research focused on the molecular and cell biology aspects of a mitochondrial disease that affects the nervous system. The findings of this study provides a firm platform for future studies that would lead to improved treatments for a number of mitochondrial disorders, and resulted in a first author publication (Bokori-Brown, M. and Holt, I.J., Rejuvenation Res 2006). During my PhD I also participated in projects to study the functional role of proteins in mitochondrial DNA maintenance utilising the technique of RNA interference (Tyynismaa, H., et al., Hum Mol Genet 2004; Sembongi, H., et al., Hum Mol Genet 2007; Iacovino, M., et al., Hum Mol Genet 2009).

In 2006 I joined the start-up biotechnology company Population Genetics Technologies Ltd., Cambridge, UK as a Postdoctoral Molecular Biologist where I gained experience in next generation sequencing technologies.

In 2007 I joined the Microbes and Disease Research Group of Prof Rick Titball, Biosciences, University of Exeter as a Research Fellow where my research focused on understanding the molecular basis of toxicity of putative virulence factors of bacterial pathogens to evaluate their potential use as vaccine candidates (funded by the Defence Science and Technology Laboratory and the Wellcome Trust). This resulted in 9 high profile publications that include: 1) characterisation of a Burkholderia pseudomallei toxin published in Science (IF: 34.661), 2) identification of key residues and a small molecule binding site of the pore forming toxin (PFT) epsilon toxin produced by the bacterial pathogen Clostridium perfringens, which resulted in a first author publication in the journal Protein Science (IF: 3.039), and 3) development of a site-directed mutant of Clostridium perfringens epsilon toxin that could form the basis of an improved recombinant vaccine against enterotoxaemia, a neurological disease of ruminants that causes significant economic losses to the farming industry worldwide, which resulted in a first author publication in the journal Vaccine (IF: 3.413). I am also a co-inventor on the patent covering candidate toxoids for vaccines against enterotoxaemia. Through molecular and cell biology studies of the PFT NetB produced by Clostridium perfringens I have contributed to the development of recombinant vaccines against avian necrotic enteritis, a disease that causes significant costs to the poultry production industry worldwide (Fernandes da Costa, S. P., et al., Avian Pathol 2016; Fernandes da Costa, S. P., et al., Toxins 2014; Fernandes da Costa, S. P., et al., Vaccine 2013; Savva, C. G., et al., J Biol Chem 2013). Both epsilon toxin and NetB recombinant vaccines are now being developed by industry. Therefore, I have contributed to the UK’s economic competitiveness.

My studies on membrane-active pore forming toxins have given me a unique opportunity to extend my research interest into the role of membrane in health and disease, and in 2013 I made the transition to inter-disciplinary research and joined the Biomedical Physics Research Group of Prof Peter Winlove, Physics, University of Exeter to investigate the biophysical aspects of the interactions of bacterial PFTs with the membrane at single cell level using a range of novel biophysical approaches, such as fluctuation spectroscopy, and membrane dipole potential and surface potential measurements. These studies, in collaboration with the University of Exeter Medical School, resulted in a first author publication in the Journal of Biological Chemistry (IF: 4.258) and was funded by the Defence Science and Technology Laboratory, UK. My current project in collaboration with cancer clinician Dr Francis Mussai, Birmingham Children’s Hospital & University of Birmingham investigates the side effects of immunotoxin therapy. This research project is funded by MedImmune LLC and I have made a significant contribution to its development.

Proteins similar to bacterial pore forming toxins also play a critical role in the immune system of the producing organism, providing defence against pathogens. In a collaboration I initiated with Dr Christos Savva, MRC Laboratory of Molecular Biology, Cambridge, I have determined the pore structure of lysenin, the defence protein of the earthworm Eisenia fetida, by single-particle cryo-electron microscopy, which resulted in a first author publication in the journal Nature Communications (IF: 11.329). This study has provided important insights into the mechanism of pore formation by the aerolysin family of β-PFTs, members of which include important bacterial virulence factors, such as epsilon toxin produced by Clostridium perfringens.

In summary, during my 11 years of active postdoctoral research experience I have published 16 peer-reviewed papers that include 6 first author publications. I have also established valuable collaborations with experts in diverse disciplines. 

 

 

Research projects

Understanding the Mechanism of Vascular Leak Syndrome Produced by Immunotoxins Targeting Acute Lymphoblastic Leukaemia. MedImmune, LLC

Effects of bacterial toxins on the electrical and mechanical properties of the plasma membrane. Defence Science and Technology Laboratory

Insights into pore formation from studies of Clostridium perfringens epsilon toxin. Wellcome Trust

Development of fluorescent reporters for imaging Burkholderia pseudomallei infections, Defence Science and Technology Laboratory

Identification, expression and characterisation of putative virulence factors of Burkholderia pseudomallei and evaluation of their potential use as vaccine candidates. Defence Science and Technology Laboratory

Publications

Key publications | Publications by category | Publications by year

Key publications


Bokori-Brown M, Martin TG, Naylor CE, Basak AK, Titball RW, Savva CG (In Press). Cryo-EM Structure of Lysenin Pore Reveals Membrane Insertion by an Aerolysin family protein. Nature Communications Full text.
Bokori-Brown M, Petrov PG, Khafaji MA, Mughal MK, Naylor CE, Shore AC, Gooding KM, Casanova F, Mitchell TJ, Titball RW, et al (2016). Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES. J Biol Chem, 291(19), 10210-10227. Abstract.  Author URL.  Full text.
Fernandes da Costa SP, Mot D, Geeraerts S, Bokori-Brown M, Van Immerseel F, Titball RW (2016). Variable protection against experimental broiler necrotic enteritis after immunization with the C-terminal fragment of Clostridium perfringens alpha-toxin and a non-toxic NetB variant. Avian Pathol, 45(3), 381-388. Abstract.  Author URL.  Full text.
Bokori-Brown M, Hall CA, Vance C, Fernandes da Costa SP, Savva CG, Naylor CE, Cole AR, Basak AK, Moss DS, Titball RW, et al (2014). Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia. Vaccine, 32(23), 2682-2687. Abstract.  Author URL.  Full text.
Fernandes da Costa SP, Savva CG, Bokori-Brown M, Naylor CE, Moss DS, Basak AK, Titball RW (2014). Identification of a key residue for oligomerisation and pore-formation of Clostridium perfringens NetB. Toxins (Basel), 6(3), 1049-1061. Abstract.  Author URL.  Full text.
Bokori-Brown M, Kokkinidou MC, Savva CG, Fernandes da Costa S, Naylor CE, Cole AR, Moss DS, Basak AK, Titball RW (2013). Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies. Protein Sci, 22(5), 650-659. Abstract.  Author URL.  Full text.

Publications by category


Journal articles

Bokori-Brown M, Martin TG, Naylor CE, Basak AK, Titball RW, Savva CG (In Press). Cryo-EM Structure of Lysenin Pore Reveals Membrane Insertion by an Aerolysin family protein. Nature Communications Full text.
Wagley S, Bokori-Brown M, Morcrette H, Malaspina A, D'Arcy C, Gnanapavan S, Lewis N, Popoff MR, Raciborska D, Nicholas R, et al (2018). Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis. Mult Scler Abstract.  Author URL.  Full text.
Bokori-Brown M, Petrov PG, Khafaji MA, Mughal MK, Naylor CE, Shore AC, Gooding KM, Casanova F, Mitchell TJ, Titball RW, et al (2016). Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES. J Biol Chem, 291(19), 10210-10227. Abstract.  Author URL.  Full text.
Fernandes da Costa SP, Mot D, Geeraerts S, Bokori-Brown M, Van Immerseel F, Titball RW (2016). Variable protection against experimental broiler necrotic enteritis after immunization with the C-terminal fragment of Clostridium perfringens alpha-toxin and a non-toxic NetB variant. Avian Pathol, 45(3), 381-388. Abstract.  Author URL.  Full text.
Bokori-Brown M, Hall CA, Vance C, Fernandes da Costa SP, Savva CG, Naylor CE, Cole AR, Basak AK, Moss DS, Titball RW, et al (2014). Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia. Vaccine, 32(23), 2682-2687. Abstract.  Author URL.  Full text.
Fernandes da Costa SP, Savva CG, Bokori-Brown M, Naylor CE, Moss DS, Basak AK, Titball RW (2014). Identification of a key residue for oligomerisation and pore-formation of Clostridium perfringens NetB. Toxins (Basel), 6(3), 1049-1061. Abstract.  Author URL.  Full text.
Bokori-Brown M, Kokkinidou MC, Savva CG, Fernandes da Costa S, Naylor CE, Cole AR, Moss DS, Basak AK, Titball RW (2013). Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies. Protein Sci, 22(5), 650-659. Abstract.  Author URL.  Full text.
Thomas RJ, Hamblin KA, Armstrong SJ, Müller CM, Bokori-Brown M, Goldman S, Atkins HS, Titball RW (2013). Galleria mellonella as a model system to test the pharmacokinetics and efficacy of antibiotics against Burkholderia pseudomallei. International Journal of Antimicrobial Agents, 41(4), 330-336. Abstract.
Savva CG, Fernandes da Costa SP, Bokori-Brown M, Naylor CE, Cole AR, Moss DS, Titball RW, Basak AK (2013). Molecular architecture and functional analysis of NetB, a pore-forming toxin from Clostridium perfringens. J Biol Chem, 288(5), 3512-3522. Abstract.  Author URL.
Fernandes da Costa SP, Mot D, Bokori-Brown M, Savva CG, Basak AK, Van Immerseel F, Titball RW (2013). Protection against avian necrotic enteritis after immunisation with NetB genetic or formaldehyde toxoids. Vaccine, 31(37), 4003-4008. Abstract.  Author URL.
Cruz A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang C-T, Dickman MJ, Essex-Lopresti A, Harding SV, Mahadi NM, et al (2011). A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A. Science, 334(6057), 821-824.
Bokori-Brown M, Savva CG, Fernandes da Costa SP, Naylor CE, Basak AK, Titball RW (2011). Molecular basis of toxicity of Clostridium perfringens epsilon toxin. FEBS J, 278(23), 4589-4601. Abstract.  Author URL.
Iacovino M, Granycome C, Sembongi H, Bokori-Brown M, Butow RA, Holt IJ, Bateman JM (2009). The conserved translocase Tim17 prevents mitochondrial DNA loss. Hum Mol Genet, 18(1), 65-74. Abstract.  Author URL.
Sembongi H, Di Re M, Bokori-Brown M, Holt IJ (2007). The yeast Holliday junction resolvase, CCE1, can restore wild-type mitochondrial DNA to human cells carrying rearranged mitochondrial DNA. Hum Mol Genet, 16(19), 2306-2314. Abstract.  Author URL.
Bokori-Brown M, Holt IJ (2006). Expression of algal nuclear ATP synthase subunit 6 in human cells results in protein targeting to mitochondria but no assembly into ATP synthase. Rejuvenation Res, 9(4), 455-469. Abstract.  Author URL.
Tyynismaa H, Sembongi H, Bokori-Brown M, Granycome C, Ashley N, Poulton J, Jalanko A, Spelbrink JN, Holt IJ, Suomalainen A, et al (2004). Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. Hum Mol Genet, 13(24), 3219-3227. Abstract.  Author URL.
Purdy D, O'Keeffe TAT, Elmore M, Herbert M, McLeod A, Bokori-Brown M, Ostrowski A, Minton NP (2002). Conjugative transfer of clostridial shuttle vectors from Escherichia coli to Clostridium difficile through circumvention of the restriction barrier. Mol Microbiol, 46(2), 439-452. Abstract.  Author URL.

Conferences

Adler D, Linden J, Ma Y, Shetty S, Bokori-Brown M, Titball R, Fetcho J, Vartanian T (2018). Clostridium perfringens induced blood-brain barrier permeability: specificity and temporal dynamics in a humanized zebrafish model.  Author URL.
Raciborska D, Turner B, Titball R, Bokori-Brown M, Wagley S, Gnanapavan S, Lewis N (2017). Epsilon toxin as a causative agent in MS.  Author URL.
Bokori-Brown M (2004). Towards stable allotopic expression of the human mitochondrial ATPase 6 (subunit a) gene.  Author URL.

Publications by year


In Press

Bokori-Brown M, Martin TG, Naylor CE, Basak AK, Titball RW, Savva CG (In Press). Cryo-EM Structure of Lysenin Pore Reveals Membrane Insertion by an Aerolysin family protein. Nature Communications Full text.

2018

Adler D, Linden J, Ma Y, Shetty S, Bokori-Brown M, Titball R, Fetcho J, Vartanian T (2018). Clostridium perfringens induced blood-brain barrier permeability: specificity and temporal dynamics in a humanized zebrafish model.  Author URL.
Wagley S, Bokori-Brown M, Morcrette H, Malaspina A, D'Arcy C, Gnanapavan S, Lewis N, Popoff MR, Raciborska D, Nicholas R, et al (2018). Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis. Mult Scler Abstract.  Author URL.  Full text.

2017

Raciborska D, Turner B, Titball R, Bokori-Brown M, Wagley S, Gnanapavan S, Lewis N (2017). Epsilon toxin as a causative agent in MS.  Author URL.

2016

Bokori-Brown M, Petrov PG, Khafaji MA, Mughal MK, Naylor CE, Shore AC, Gooding KM, Casanova F, Mitchell TJ, Titball RW, et al (2016). Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES. J Biol Chem, 291(19), 10210-10227. Abstract.  Author URL.  Full text.
Fernandes da Costa SP, Mot D, Geeraerts S, Bokori-Brown M, Van Immerseel F, Titball RW (2016). Variable protection against experimental broiler necrotic enteritis after immunization with the C-terminal fragment of Clostridium perfringens alpha-toxin and a non-toxic NetB variant. Avian Pathol, 45(3), 381-388. Abstract.  Author URL.  Full text.

2014

Bokori-Brown M, Hall CA, Vance C, Fernandes da Costa SP, Savva CG, Naylor CE, Cole AR, Basak AK, Moss DS, Titball RW, et al (2014). Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia. Vaccine, 32(23), 2682-2687. Abstract.  Author URL.  Full text.
Fernandes da Costa SP, Savva CG, Bokori-Brown M, Naylor CE, Moss DS, Basak AK, Titball RW (2014). Identification of a key residue for oligomerisation and pore-formation of Clostridium perfringens NetB. Toxins (Basel), 6(3), 1049-1061. Abstract.  Author URL.  Full text.

2013

Bokori-Brown M, Kokkinidou MC, Savva CG, Fernandes da Costa S, Naylor CE, Cole AR, Moss DS, Basak AK, Titball RW (2013). Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies. Protein Sci, 22(5), 650-659. Abstract.  Author URL.  Full text.
Thomas RJ, Hamblin KA, Armstrong SJ, Müller CM, Bokori-Brown M, Goldman S, Atkins HS, Titball RW (2013). Galleria mellonella as a model system to test the pharmacokinetics and efficacy of antibiotics against Burkholderia pseudomallei. International Journal of Antimicrobial Agents, 41(4), 330-336. Abstract.
Savva CG, Fernandes da Costa SP, Bokori-Brown M, Naylor CE, Cole AR, Moss DS, Titball RW, Basak AK (2013). Molecular architecture and functional analysis of NetB, a pore-forming toxin from Clostridium perfringens. J Biol Chem, 288(5), 3512-3522. Abstract.  Author URL.
Fernandes da Costa SP, Mot D, Bokori-Brown M, Savva CG, Basak AK, Van Immerseel F, Titball RW (2013). Protection against avian necrotic enteritis after immunisation with NetB genetic or formaldehyde toxoids. Vaccine, 31(37), 4003-4008. Abstract.  Author URL.

2011

Cruz A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang C-T, Dickman MJ, Essex-Lopresti A, Harding SV, Mahadi NM, et al (2011). A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A. Science, 334(6057), 821-824.
Bokori-Brown M, Savva CG, Fernandes da Costa SP, Naylor CE, Basak AK, Titball RW (2011). Molecular basis of toxicity of Clostridium perfringens epsilon toxin. FEBS J, 278(23), 4589-4601. Abstract.  Author URL.

2009

Iacovino M, Granycome C, Sembongi H, Bokori-Brown M, Butow RA, Holt IJ, Bateman JM (2009). The conserved translocase Tim17 prevents mitochondrial DNA loss. Hum Mol Genet, 18(1), 65-74. Abstract.  Author URL.

2007

Sembongi H, Di Re M, Bokori-Brown M, Holt IJ (2007). The yeast Holliday junction resolvase, CCE1, can restore wild-type mitochondrial DNA to human cells carrying rearranged mitochondrial DNA. Hum Mol Genet, 16(19), 2306-2314. Abstract.  Author URL.

2006

Bokori-Brown M, Holt IJ (2006). Expression of algal nuclear ATP synthase subunit 6 in human cells results in protein targeting to mitochondria but no assembly into ATP synthase. Rejuvenation Res, 9(4), 455-469. Abstract.  Author URL.

2004

Bokori-Brown M (2004). Towards stable allotopic expression of the human mitochondrial ATPase 6 (subunit a) gene.  Author URL.
Tyynismaa H, Sembongi H, Bokori-Brown M, Granycome C, Ashley N, Poulton J, Jalanko A, Spelbrink JN, Holt IJ, Suomalainen A, et al (2004). Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. Hum Mol Genet, 13(24), 3219-3227. Abstract.  Author URL.

2002

Purdy D, O'Keeffe TAT, Elmore M, Herbert M, McLeod A, Bokori-Brown M, Ostrowski A, Minton NP (2002). Conjugative transfer of clostridial shuttle vectors from Escherichia coli to Clostridium difficile through circumvention of the restriction barrier. Mol Microbiol, 46(2), 439-452. Abstract.  Author URL.

Monika_Bokori-Brown Details from cache as at 2018-12-18 09:43:26

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