Dr Monika Bokori-Brown
+44(0)1392 72 5177
Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK
Broad research specialisms:
- Molecular cell biology
- Bacterial protein toxins
- Membrane biophysics
- Microbial pathogenesis
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
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
I am a molecular cell biologist by training but over the past six 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 and last author publications in high impact journals, such as Nature Communications.
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). These studies resulted in ten high profile publications that include four first author, peer-reviewed publications (FEBS J 2011, Protein Sci 2013, Vaccine 2014, and NPJ Vaccines 2019). I am also a co-inventor on four patents, one of which is at the early stages of being taken up by industry to develop next-generation veterinary vaccines against enterotoxaemia, a neurological disease of ruminants that causes significant economic losses to the farming industry worldwide. Through molecular and cell biology studies of the pore-froming toxin NetB produced by Clostridium perfringens I have also 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).
My research 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 pore-forming toxins 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 have resulted in two first author publications in high impact journals (J Biol Chem 2016, and Front Oncol 2018) and have demonstrated, for the first time, a correlation between toxin activity and membrane physical properties, providing the framework for the development of new approaches to treat bacterial infections. Further research in collaboration with cancer clinician Dr Francis Mussai, Birmingham Children’s Hospital & University of Birmingham unraveled the mechanisms responsible for the side effects of immunotoxin cancer therapy that will inform the development of next-generation immunotoxins. This research project was funded by MedImmune LLC, MRC Proximity to Discovery Industry Engagement Fund, Royal Devon & Exeter Small Grant and Open Innovation Platform Strategic Fund, and I have made a significant contribution to their 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 collaboration with Dr Christos Savva (University of Leicester), 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 (2016). Further collaboration with Dr Christos Savva (University of Leicester) have determined the atomic resolution structure of Clostridium perfringens epsilon toxin in its membrane-inserted, oligomeric pore form using cryo-electron microscopy. This study will have important implications for developing novel therapeutics to prevent human and animal neurological diseases caused by epsilon toxin.
In summary, during my 13 years of active postdoctoral research experience I have published 21 peer-reviewed, high impact publications that include seven first author publications and one corresponding, last author publication in Nature Communications.
My current multidisciplinary research project funded by BBSRC investigates the molecular basis of toxicity of Clostridium perfringens epsilon toxin, which will have important implications for the development of next-generation veterinary glycoconjugate vaccines.
Glycoengineering of Veterinary Vaccines (GoVV), BBSRC
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
Prof Min Dong, Harvard Medical School, Boston, MA, USA
Dr Andreas Rummel, Hannover Medical School, Hannover, Germany
Prof Horst Posthaus, Institute of Veterinary Pathology, University of Bern, Switzerland
Dr Chris Lorenz, Physics, King’s College London, UK
Prof Christian Soeller, Living Systems Institute, University of Exeter, UK
Prof Frank Vollmer, Living Systems Institute, University of Exeter, UK
Dr Catalin Chimerel, Living Systems Institute, University of Exeter, UK
Prof Tim Vartanian, Weill Cornell Medical College of Cornell University, New York, USA
Dr Francis Mussai, University of Birmingham, UK
Dr Christos G. Savva, University of Leicester, UK
Dr Jeremy Metz, University of Exeter, UK