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Dr Claudia Hemsley   (nee Mueller )

Dr Claudia Hemsley (nee Mueller )

Postdoctoral Research Fellow

 5177

 01392 725177

 Geoffrey Pope 401

 

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

 Office hours:

I usually work from Tuesday to Friday only

My interest in bacterial pathogenesis and infectious diseases developed during my Master’s degree, where I studied the effect of environmental conditions on fimbriation of uropathogenic E. coli. My PhD studies and my first post-doctoral project had the broader theme of global gene regulation processes in uropathogenic E. coli.

Since joining Prof. Titball’s group in Exeter, I have studied virulence and antibiotic resistance mechanisms of Burkholderia pseudomallei, a more “unusual” pathogen causing the life-threatening disease melioidosis, as well as Coxiella burnetii, the causative agent of the zoonotic disease Q-fever.

Within the Bacterial Pathogenesis Research Group, I have co-supervised and mentored several third year project students and PhD students.

Broad research specialisms:

  • Bacterial pathogenesis
  • Antimicrobial therapy
  • Gene regulation
  • Genomics

Qualifications

MSc. in Molecular Biology, University of Umea, Sweden
PhD in Molecular Biology, Institute of Molecular Biology of Infectious Diseases, Würzburg, Germany

Research

Research interests

My current research project funded by DSTL aims to characterise Coxiella burnetii at the molecular level. C. burnetii is an obligate intracellular bacterium that causes the zoonotic disease Q-fever in humans. C. burnetii is difficult to culture, requires containment in a Biological Safety Lavel 3 (BSL3) laboratory, and is difficult to modify genetically. I have successfuly established culturing and genetic techniques for workig with Coxiella here in Exeter. I am in the process of characterising essential and virulence-associated genes in this organism by using traditional genetic techniques and Transposon Directed Insertion Site Sequencing (TraDIS) and am trying to establish the genetic diversity of C. burnetii in the UK by whole genome sequencing.

Previous research projects were focussed on Burkholderia pseudomallei, another BSL3 organisms. The genus Burkholderia contains several pathogenic bacterial species causing severe infections in humans that cannot easily be treated with antibiotics and often enter a chronic or latent state. One aim of my research was to identify the molecular basis that enables B. pseudomallei to cause chronic disease. Target genes selected from published data or our own transcriptomic data were subject to mutagenesis and the virulence potential of the resulting mutant derivatives was then tested in various models of disease.

A second, related aim of my research was to study the contribution of so-called “persister cells” in treatment failure and recurrent or chronic disease. Persister cells are a subpopulation of multidrug-tolerant phenotypic variants in bacterial populations. The mechanism of persister cell formation is not well understood but it is thought that persisters are able to withstand antibiotics due to an altered metabolism. Here, we have used B. thailandensis as a model system for studying non-inherited antibiotic resistance mechanisms in the genus Burkholderia in more detail, including transcriptomic and metabolic profiling of persister cells and mathematical modelling of alternative antibiotic treatment regimes that could eradicate these phenotypic variants.

Research projects

  • Mechanisms of persistence and chronic disease caused by Burkholderia pseudomallei
  • In vitro persister cell formation in B. thailandensis
  • Identification of novel targets for antimicrobial therapy using small molecule inhibitors
  • Molecular characterisation of Coxiella burnetii

Grants/Funding:

  • Wellcome Trust (Award WT085162AIA)
  • Defence Science and Technology Laboratory (DSTL)

Key publications | Publications by category | Publications by year

Publications by category


Journal articles

Champion OL, Gourlay LJ, Scott AE, Lassaux P, Conejero L, Perletti L, Hemsley C, Prior J, Bancroft G, Bolognesi M, et al (2016). Immunisation with proteins expressed during chronic murine melioidosis provides enhanced protection against disease. Vaccine, 34(14), 1665-1671. Abstract.  Author URL.  Full text.
Anutrakunchai C, Hemsley CM, Sermswan RW, Titball RW, Chareonsudjai S, Taweechaisupapong S (2016). Role of RelA and SpoT in Burkholderia pseudomallei survival, biofilm formation and ceftazidime tolerance during nutritional stress. Tropical Biomedicine, 33(4), 786-798. Abstract.  Full text.
Hemsley CM, Luo JX, Andreae CA, Butler CS, Soyer OS, Titball RW (2014). Bacterial drug tolerance under clinical conditions is governed by anaerobic adaptation but not anaerobic respiration. Antimicrob Agents Chemother, 58(10), 5775-5783. Abstract.  Author URL.  Full text.
Moule MG, Hemsley CM, Seet Q, Guerra-Assunção JA, Lim J, Sarkar-Tyson M, Clark TG, Tan PBO, Titball RW, Cuccui J, et al (2014). Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development. mBio, 5(1). Abstract.
Moule MG, Hemsley CM, Seet Q, Guerra-Assunção JA, Lim J, Sarkar-Tyson M, Clark TG, Tan PBO, Titball RW, Cuccui J, et al (2014). Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development. MBio, 5(1), e00926-e00913. Abstract.  Author URL.  Full text.
Butt A, Higman VA, Williams C, Crump MP, Hemsley CM, Harmer N, Titball RW (2014). The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation. Biochem J, 459(2), 333-344. Abstract.  Author URL.  Full text.
Wagley S, Hemsley C, Thomas R, Moule MG, Vanaporn M, Andreae C, Robinson M, Goldman S, Wren BW, Butler CS, et al (2014). The twin arginine translocation system is essential for aerobic growth and full virulence of Burkholderia thailandensis. J Bacteriol, 196(2), 407-416. Abstract.  Author URL.
Jitprasutwit S, Ong C, Juntawieng N, Ooi WF, Hemsley CM, Vattanaviboon P, Titball RW, Tan P, Korbsrisate S (2014). Transcriptional profiles of Burkholderia pseudomallei reveal the direct and indirect roles of Sigma E under oxidative stress conditions. BMC Genomics, 15(1). Abstract.
Jitprasutwit S, Ong C, Juntawieng N, Ooi WF, Hemsley CM, Vattanaviboon P, Titball RW, Tan P, Korbsrisate S (2014). Transcriptional profiles of Burkholderia pseudomallei reveal the direct and indirect roles of Sigma E under oxidative stress conditions. BMC Genomics, 15 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. Int J Antimicrob Agents, 41(4), 330-336. Abstract.  Author URL.
Butt A, Müller C, Harmer N, Titball RW (2013). Identification of type II toxin-antitoxin modules in Burkholderia pseudomallei. FEMS Microbiol Lett, 338(1), 86-94. Abstract.  Author URL.  Full text.
Ooi WF, Ong C, Nandi T, Kreisberg JF, Chua HH, Sun G, Chen Y, Mueller C, Conejero L, Eshaghi M, et al (2013). The condition-dependent transcriptional landscape of Burkholderia pseudomallei. PLoS Genet, 9(9). Abstract.  Author URL.  Full text.
Müller CM, Conejero L, Spink N, Wand ME, Bancroft GJ, Titball RW (2012). Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity. Infect. Immun., 80(9), 3247-3255. Abstract.  Author URL.  Full text.
Debieux CM, Dridge EJ, Mueller CM, Splatt P, Paszkiewicz K, Knight I, Florance H, Love J, Titball RW, Lewis RJ, et al (2011). A bacterial process for selenium nanosphere assembly. Proc Natl Acad Sci U S A, 108(33), 13480-13485. Abstract.  Author URL.  Full text.
Wand ME, Müller CM, Titball RW, Michell SL (2011). Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis. BMC Microbiol, 11(1). Abstract.  Author URL.  Full text.
Müller CM, Schneider G, Dobrindt U, Emödy L, Hacker J, Uhlin BE (2010). Differential effects and interactions of endogenous and horizontally acquired H-NS-like proteins in pathogenic Escherichia coli. , 75(2), 280-293. Abstract.  Author URL.  Full text.
Sjöström AE, Sondén B, Müller C, Rydström A, Dobrindt U, Wai SN, Uhlin BE (2009). Analysis of the sfaXII locus in the Escherichia coli meningitis isolate IHE3034 reveals two novel regulatory genes within the promoter-distal region of the main S fimbrial operon. , 46, 150-158. Abstract.  Author URL.
Müller CM, Åberg A, Straseviçiene J, Emődy L, Uhlin BE, Balsalobre C (2009). Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP. , 5(2). Abstract.  Author URL.  Full text.
Müller CM, Dobrindt U, Nagy G, Emődy L, Uhlin BE, Hacker J (2006). Role of Histone-Like Proteins H-NS and StpA in Expression of Virulence Determinants of Uropathogenic Escherichia coli. , 188(15), 5428-5438. Abstract.  Author URL.

Publications by year


2016

Champion OL, Gourlay LJ, Scott AE, Lassaux P, Conejero L, Perletti L, Hemsley C, Prior J, Bancroft G, Bolognesi M, et al (2016). Immunisation with proteins expressed during chronic murine melioidosis provides enhanced protection against disease. Vaccine, 34(14), 1665-1671. Abstract.  Author URL.  Full text.
Anutrakunchai C, Hemsley CM, Sermswan RW, Titball RW, Chareonsudjai S, Taweechaisupapong S (2016). Role of RelA and SpoT in Burkholderia pseudomallei survival, biofilm formation and ceftazidime tolerance during nutritional stress. Tropical Biomedicine, 33(4), 786-798. Abstract.  Full text.

2014

Hemsley CM, Luo JX, Andreae CA, Butler CS, Soyer OS, Titball RW (2014). Bacterial drug tolerance under clinical conditions is governed by anaerobic adaptation but not anaerobic respiration. Antimicrob Agents Chemother, 58(10), 5775-5783. Abstract.  Author URL.  Full text.
Moule MG, Hemsley CM, Seet Q, Guerra-Assunção JA, Lim J, Sarkar-Tyson M, Clark TG, Tan PBO, Titball RW, Cuccui J, et al (2014). Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development. mBio, 5(1). Abstract.
Moule MG, Hemsley CM, Seet Q, Guerra-Assunção JA, Lim J, Sarkar-Tyson M, Clark TG, Tan PBO, Titball RW, Cuccui J, et al (2014). Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development. MBio, 5(1), e00926-e00913. Abstract.  Author URL.  Full text.
Butt A, Higman VA, Williams C, Crump MP, Hemsley CM, Harmer N, Titball RW (2014). The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation. Biochem J, 459(2), 333-344. Abstract.  Author URL.  Full text.
Wagley S, Hemsley C, Thomas R, Moule MG, Vanaporn M, Andreae C, Robinson M, Goldman S, Wren BW, Butler CS, et al (2014). The twin arginine translocation system is essential for aerobic growth and full virulence of Burkholderia thailandensis. J Bacteriol, 196(2), 407-416. Abstract.  Author URL.
Jitprasutwit S, Ong C, Juntawieng N, Ooi WF, Hemsley CM, Vattanaviboon P, Titball RW, Tan P, Korbsrisate S (2014). Transcriptional profiles of Burkholderia pseudomallei reveal the direct and indirect roles of Sigma E under oxidative stress conditions. BMC Genomics, 15(1). Abstract.
Jitprasutwit S, Ong C, Juntawieng N, Ooi WF, Hemsley CM, Vattanaviboon P, Titball RW, Tan P, Korbsrisate S (2014). Transcriptional profiles of Burkholderia pseudomallei reveal the direct and indirect roles of Sigma E under oxidative stress conditions. BMC Genomics, 15 Abstract.  Author URL.  Full text.

2013

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. Int J Antimicrob Agents, 41(4), 330-336. Abstract.  Author URL.
Butt A, Müller C, Harmer N, Titball RW (2013). Identification of type II toxin-antitoxin modules in Burkholderia pseudomallei. FEMS Microbiol Lett, 338(1), 86-94. Abstract.  Author URL.  Full text.
Ooi WF, Ong C, Nandi T, Kreisberg JF, Chua HH, Sun G, Chen Y, Mueller C, Conejero L, Eshaghi M, et al (2013). The condition-dependent transcriptional landscape of Burkholderia pseudomallei. PLoS Genet, 9(9). Abstract.  Author URL.  Full text.

2012

Müller CM, Conejero L, Spink N, Wand ME, Bancroft GJ, Titball RW (2012). Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity. Infect. Immun., 80(9), 3247-3255. Abstract.  Author URL.  Full text.

2011

Debieux CM, Dridge EJ, Mueller CM, Splatt P, Paszkiewicz K, Knight I, Florance H, Love J, Titball RW, Lewis RJ, et al (2011). A bacterial process for selenium nanosphere assembly. Proc Natl Acad Sci U S A, 108(33), 13480-13485. Abstract.  Author URL.  Full text.
Wand ME, Müller CM, Titball RW, Michell SL (2011). Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis. BMC Microbiol, 11(1). Abstract.  Author URL.  Full text.

2010

Müller CM, Schneider G, Dobrindt U, Emödy L, Hacker J, Uhlin BE (2010). Differential effects and interactions of endogenous and horizontally acquired H-NS-like proteins in pathogenic Escherichia coli. , 75(2), 280-293. Abstract.  Author URL.  Full text.

2009

Sjöström AE, Sondén B, Müller C, Rydström A, Dobrindt U, Wai SN, Uhlin BE (2009). Analysis of the sfaXII locus in the Escherichia coli meningitis isolate IHE3034 reveals two novel regulatory genes within the promoter-distal region of the main S fimbrial operon. , 46, 150-158. Abstract.  Author URL.
Müller CM, Åberg A, Straseviçiene J, Emődy L, Uhlin BE, Balsalobre C (2009). Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP. , 5(2). Abstract.  Author URL.  Full text.

2006

Müller CM, Dobrindt U, Nagy G, Emődy L, Uhlin BE, Hacker J (2006). Role of Histone-Like Proteins H-NS and StpA in Expression of Virulence Determinants of Uropathogenic Escherichia coli. , 188(15), 5428-5438. Abstract.  Author URL.

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