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About me
I graduated in Biological Sciences (B.Sc, University of Salford, 1997, 1st Class) prior to undertaking a Ph.D in molecular microbiology studying quorum sensing in Pseudomonas aeruginosa (University of Nottingham, 2001). I worked as a Postdoctoral Fellow at Nottingham on both EU and BBSRC funded grants, before obtaining a Royal Society University Fellowship (2006-2014). I was promoted to Associate Professor in 2013. In April 2017 I moved to the School of Biological Sciences at Georgia Tech as an Associate Professor. I currently serve as a Senior Editor on the editorial board of Microbiology. I have previously served on the editorial boards of FEMS Microbiology Letters, BMC Microbiology, Microbiology Open and Royal Society Open Science. I was an elected member of the Microbiology Society Council (2012-2016) and also served on their conference and policy committees. In my spare time I play bass guitar. I recorded some original music in a band called Meaner and I currently play in a covers band in Atlanta. |
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Current Research Interests
I am interested in cooperation and communication in microbes and how these are related to virulence, biofilms and antimicrobial resistance. I have a long standing interest in understanding how the opportunistic pathogen Pseudomonas aeruginosa causes disease, and am especially interested in how this organism evolves during chronic infections such as those found in cystic fibrosis lungs and chronic wounds. See here for the latest work from my group.
Awards
I was awarded the 2010 Fleming Prize by the Microbiology Society.
Education & Employment
- Associate Professor. Georgia Institute of Technology, Atlanta, U.S.A. (From April 2017)
- Associate Professor in Sociomicrobiology. University of Nottingham, U.K. (2013-2017)
- Royal Society University Research Fellow. University of Nottingham, U.K. (2006-2014)
- Postdoctoral Research Fellow. University of Nottingham, U.K. (2001-2006)
- PhD in Molecular Microbiology. University of Nottingham, U.K. (1997-2001)
- BSc (Hons) in Biological Sciences. University of Salford, U.K. (1993-1997)
- Scientific Officer. Paterson Institute for Cancer Research, Manchester, U.K. (1990-1993)
- Medical Laboratory Assistant. Withington Hospital, Manchester, U.K. (1989-1990)
- Laboratory Assistant. Manchester Comparative Reagents, Stockport, U.K. (1987-1989)
Current and previous teaching roles
- Teacher for Bacterial Pathogenesis (BIOL8801) (Georgia Tech)
- Teacher for Special Topics (BIOL8803) (Georgia Tech)
- Teacher for Communicating Biological Research (BIOS4460) (Georgia Tech)
- Teacher for Medical Microbiology (BIOS4340) (Georgia Tech)
- Teacher for General Ecology (BIOL2335) (Georgia Tech)
- Microbiology module lead for the BMedSci course (University of Nottingham)
- Parasitology & Mycology module coordinator for a distance learning MSc course (University of Nottingham)
- Module coordinator for Pathogens (University of Nottingham)
Admin roles (Georgia Tech only)
- Institutional Biosafety Committee (IBC) (2021 - present)
- Outreach and Communication for the Center for Microbial Dynamics & Infection (2020 - present)
- Member of the Biological Sciences Seminar Committee (2017 - present)
I am interested in cooperation and communication in microbes and how these are related to virulence, biofilms and antimicrobial resistance. I have a long standing interest in understanding how the opportunistic pathogen Pseudomonas aeruginosa causes disease, and am especially interested in how this organism evolves during chronic infections such as those found in cystic fibrosis lungs and chronic wounds. See here for the latest work from my group.
Awards
I was awarded the 2010 Fleming Prize by the Microbiology Society.
Education & Employment
- Associate Professor. Georgia Institute of Technology, Atlanta, U.S.A. (From April 2017)
- Associate Professor in Sociomicrobiology. University of Nottingham, U.K. (2013-2017)
- Royal Society University Research Fellow. University of Nottingham, U.K. (2006-2014)
- Postdoctoral Research Fellow. University of Nottingham, U.K. (2001-2006)
- PhD in Molecular Microbiology. University of Nottingham, U.K. (1997-2001)
- BSc (Hons) in Biological Sciences. University of Salford, U.K. (1993-1997)
- Scientific Officer. Paterson Institute for Cancer Research, Manchester, U.K. (1990-1993)
- Medical Laboratory Assistant. Withington Hospital, Manchester, U.K. (1989-1990)
- Laboratory Assistant. Manchester Comparative Reagents, Stockport, U.K. (1987-1989)
Current and previous teaching roles
- Teacher for Bacterial Pathogenesis (BIOL8801) (Georgia Tech)
- Teacher for Special Topics (BIOL8803) (Georgia Tech)
- Teacher for Communicating Biological Research (BIOS4460) (Georgia Tech)
- Teacher for Medical Microbiology (BIOS4340) (Georgia Tech)
- Teacher for General Ecology (BIOL2335) (Georgia Tech)
- Microbiology module lead for the BMedSci course (University of Nottingham)
- Parasitology & Mycology module coordinator for a distance learning MSc course (University of Nottingham)
- Module coordinator for Pathogens (University of Nottingham)
Admin roles (Georgia Tech only)
- Institutional Biosafety Committee (IBC) (2021 - present)
- Outreach and Communication for the Center for Microbial Dynamics & Infection (2020 - present)
- Member of the Biological Sciences Seminar Committee (2017 - present)
Previous PhD and Postdoctoral research (2000 - 2006)
During my post-graduate studies and future post-doctoral positions, I studied cell-to-cell communication via diffusible signal molecules (quorum sensing) in the opportunistic pathogen Pseudomonas aeruginosa. This problematic organism, which is a leading cause of death in patients with Cystic Fibrosis, utilises three intertwined quorum sensing systems, two N-acyl homoserine lactone (AHL)-based and the Pseudomonas quinolone signal (PQS) to regulate virulence factor production.
We demonstrated that the cytotoxic lectin (LecA) is strictly dependent on AHLs (Winzer et al. 2000) and PQS (Diggle et al. 2003). To unravel the increasing complexity of the quorum sensing genetic circuitry in P. aeruginosa, I used a lecA::luxCDABE fusion and subjected it to random transposon mutagenesis. This set of experiments revealed a novel negative regulator of lecA expression, MvaT, previously undescribed in P. aeruginosa, which was subsequently shown to influence AHL and virulence factor levels (Diggle et al. 2002). A search of the available microbial genomes revealed that MvaT was restricted to the Pseudomonad's and many of these species contained at least one homologue (Vallet et al. 2004). In collaboration with Alain Filloux at the CNRS in Marseille, we found that a mutation in mvaT results in enhanced biofilm formation due to up-regulation of the fimbrial cup gene cluster (Vallet et al. 2004). Furthermore we showed (in collaboration with Abdul Hamood, Texas) that MvaT binds directly to the promoter region of ptxS, a gene involved in the regulation of exotoxin A (Westfall et al. 2004). A microarray analysis revealed that a mutation in mvaT resulted in the transcriptional change of over 200 genes (Vallet et al. 2004). It therefore appears that MvaT is involved in many cellular processes and indeed, it has now been shown by other workers that MvaT proteins are HN-S like in nature and these types of proteins regulate a variety of functions in other species of bacteria.
My work also revealed that the galactophilic lectin LecA is involved in the formation of mature P. aeruginosa biofilms. Interestingly, such biofilms can be prevented and even dispersed by the addition of hydrophobic galactosides to the growth medium (Diggle et al. 2006). It is assumed that these sugars compete with sugars on the cell surface for LecA binding and so prevent cell to cell interactions. This work may lead to simple yet effective methods to eradicate P. aeruginosa biofilms which are economically important in the medical environment where they colonise catheters and other in-dwelling devices, and also are important in the cystic fibrosis lung being the leading cause of mortality. Furthermore, biofilms remain problematic in industry where they often grow in industrial pipes. Treating pipes with sugars offers a cheap and safe solution to such problems. We have shown that inhibitors designed against the fucose-specific lectin LecB can significantly reduce biofilm formation (Johansson et al. 2009). Another way of disrupting biofilms may come from interrupting quorum sensing signalling (quorum quenching). We described an AHL acylase PvdQ (PA2385), which degrades long chain AHLs (Sio et al. 2006). When overexpressed, this acylase significantly reduced virulence factor production.
P. aeruginosa also produces over 50 2-alkyl-4-quinolones (AQs), some of which were originally identified from their antibacterial properties (Diggle et al. 2006; Dubern & Diggle 2008; Heeb et al. 2011). One of these compounds, 2-heptyl-3-hydroxy-4-quinolone was discovered to function as a diffusible signal molecule and termed the pseudomonas quinolone signal (PQS). I demonstrated that PQS is essential for the production of several key virulence factors including LecA (Diggle et al. 2003). In collaboration with Pierre Cornelis from the University of Brussels I was involved in the identification of an efflux pump which facilitates cell-to-cell communication, antibiotic susceptibility and growth of P. aeruginosa (Aendekerk et al. 2005). Interestingly, addition of PQS to pump mutants completely restored growth, antibiotic susceptibility and virulence although the exact mechanism remains a mystery (Aendekerk et al. 2005). Microarray analysis also revealed that PQS has a dual role as both an iron chelator and a signal molecule, and that the PQS precursor HHQ can also function as a direct signal (Diggle et al. 2007). The PQS-Fe complex plays an important role in the P. aeruginosa killing of C. elegans (Zaborin et al. 2009).
I constructed a biosensor capable of detecting PQS and other related AQs from P. aeruginosa (Fletcher et al. 2007a; Fletcher et al. 2007b; Diggle et al. 2011). A screen of a number of Pseudomonas and Burkholderia species (including the important human pathogen Burkholderia pseudomallei), revealed that several species made the immediate PQS precursor molecule HHQ (Diggle et al. 2006). This data was significant as it demonstrated for the first time, a role for AQs in bacterial cell-to-cell communication beyond P. aeruginosa. Other work with B. pseudomallei identified a number of AHLs produced by this organism and a role for QS in the response to oxidative stress (Lumjiaktase et al. 2006). We have comprehensively reviewed AQ QS in P. aeruginosa and other organisms (Diggle et al. 2006; Dubern & Diggle 2008; Heeb et al. 2011).
During my post-graduate studies and future post-doctoral positions, I studied cell-to-cell communication via diffusible signal molecules (quorum sensing) in the opportunistic pathogen Pseudomonas aeruginosa. This problematic organism, which is a leading cause of death in patients with Cystic Fibrosis, utilises three intertwined quorum sensing systems, two N-acyl homoserine lactone (AHL)-based and the Pseudomonas quinolone signal (PQS) to regulate virulence factor production.
We demonstrated that the cytotoxic lectin (LecA) is strictly dependent on AHLs (Winzer et al. 2000) and PQS (Diggle et al. 2003). To unravel the increasing complexity of the quorum sensing genetic circuitry in P. aeruginosa, I used a lecA::luxCDABE fusion and subjected it to random transposon mutagenesis. This set of experiments revealed a novel negative regulator of lecA expression, MvaT, previously undescribed in P. aeruginosa, which was subsequently shown to influence AHL and virulence factor levels (Diggle et al. 2002). A search of the available microbial genomes revealed that MvaT was restricted to the Pseudomonad's and many of these species contained at least one homologue (Vallet et al. 2004). In collaboration with Alain Filloux at the CNRS in Marseille, we found that a mutation in mvaT results in enhanced biofilm formation due to up-regulation of the fimbrial cup gene cluster (Vallet et al. 2004). Furthermore we showed (in collaboration with Abdul Hamood, Texas) that MvaT binds directly to the promoter region of ptxS, a gene involved in the regulation of exotoxin A (Westfall et al. 2004). A microarray analysis revealed that a mutation in mvaT resulted in the transcriptional change of over 200 genes (Vallet et al. 2004). It therefore appears that MvaT is involved in many cellular processes and indeed, it has now been shown by other workers that MvaT proteins are HN-S like in nature and these types of proteins regulate a variety of functions in other species of bacteria.
My work also revealed that the galactophilic lectin LecA is involved in the formation of mature P. aeruginosa biofilms. Interestingly, such biofilms can be prevented and even dispersed by the addition of hydrophobic galactosides to the growth medium (Diggle et al. 2006). It is assumed that these sugars compete with sugars on the cell surface for LecA binding and so prevent cell to cell interactions. This work may lead to simple yet effective methods to eradicate P. aeruginosa biofilms which are economically important in the medical environment where they colonise catheters and other in-dwelling devices, and also are important in the cystic fibrosis lung being the leading cause of mortality. Furthermore, biofilms remain problematic in industry where they often grow in industrial pipes. Treating pipes with sugars offers a cheap and safe solution to such problems. We have shown that inhibitors designed against the fucose-specific lectin LecB can significantly reduce biofilm formation (Johansson et al. 2009). Another way of disrupting biofilms may come from interrupting quorum sensing signalling (quorum quenching). We described an AHL acylase PvdQ (PA2385), which degrades long chain AHLs (Sio et al. 2006). When overexpressed, this acylase significantly reduced virulence factor production.
P. aeruginosa also produces over 50 2-alkyl-4-quinolones (AQs), some of which were originally identified from their antibacterial properties (Diggle et al. 2006; Dubern & Diggle 2008; Heeb et al. 2011). One of these compounds, 2-heptyl-3-hydroxy-4-quinolone was discovered to function as a diffusible signal molecule and termed the pseudomonas quinolone signal (PQS). I demonstrated that PQS is essential for the production of several key virulence factors including LecA (Diggle et al. 2003). In collaboration with Pierre Cornelis from the University of Brussels I was involved in the identification of an efflux pump which facilitates cell-to-cell communication, antibiotic susceptibility and growth of P. aeruginosa (Aendekerk et al. 2005). Interestingly, addition of PQS to pump mutants completely restored growth, antibiotic susceptibility and virulence although the exact mechanism remains a mystery (Aendekerk et al. 2005). Microarray analysis also revealed that PQS has a dual role as both an iron chelator and a signal molecule, and that the PQS precursor HHQ can also function as a direct signal (Diggle et al. 2007). The PQS-Fe complex plays an important role in the P. aeruginosa killing of C. elegans (Zaborin et al. 2009).
I constructed a biosensor capable of detecting PQS and other related AQs from P. aeruginosa (Fletcher et al. 2007a; Fletcher et al. 2007b; Diggle et al. 2011). A screen of a number of Pseudomonas and Burkholderia species (including the important human pathogen Burkholderia pseudomallei), revealed that several species made the immediate PQS precursor molecule HHQ (Diggle et al. 2006). This data was significant as it demonstrated for the first time, a role for AQs in bacterial cell-to-cell communication beyond P. aeruginosa. Other work with B. pseudomallei identified a number of AHLs produced by this organism and a role for QS in the response to oxidative stress (Lumjiaktase et al. 2006). We have comprehensively reviewed AQ QS in P. aeruginosa and other organisms (Diggle et al. 2006; Dubern & Diggle 2008; Heeb et al. 2011).