Professor Ruth Massey
Welcome to the Massey Microbial Pathogenicity Laboratory
The Massey Lab is interested in understanding the means by which major human pathogens cause disease. Focusing primarily on the Gram positive organisms Staphylococcus aureus and Streptococcus pneumoniae the group studies how these bacteria cause damage to their human hosts at both population and molecular levels. We utilise whole genome sequenced data for collections of infecting strains and interrogate this for genetic features that associated with more severe patient outcomes following infections. Using molecular and cell biology techniques we then characterise the molecular basis of how these associated genetic feature contribute to the disease process.
Qualifications and Career History
- 1999: PhD Moyne Institute of Preventative Medicine, Trinity College Dublin, Ireland.
- 1998-2003: Post-doctoral Researcher, University of Oxford, UK.
- 2003-2004: Post-doctoral Researcher, University of Bath, UK.
- 2004-2007: Departmental Lecturer, University of Oxford.
- 2007-2017: Reader at the University of Bath.
- 2017-2019: Reader at the University of Bristol.
- 2019-present: Professor at the University of Bristol.
Infectious diseases remain one of the greatest causes of morbidity and mortality globally despite on-going efforts to develop effective antimicrobials and preventative vaccines. With increasing rates of antimicrobial resistance (AMR), dwindling pools of effective antibiotics, and many pharmaceutical companies shutting down their antibiotic development facilities, new approaches to infection management and treatment regimens are desperately needed. However, without a more comprehensive and multi-dimensional understanding of how pathogens cause disease, we are largely working in the dark.
The establishment of an infection and the subsequent development of disease are complex multifactorial processes involving the pathogen, the host and their respective environments. Until recently, the analysis of this complexity necessarily required the adoption of a reductionist approach, focusing on individual aspects in isolation and often by means of model systems. However, neglecting all other potentially interacting features can make extrapolation of research findings to real-life situations almost impossible. Ultimately, what is needed is a detailed understanding of all the features and processes that lead to the development of diseases in humans living in the real world, with all the variability and diversity that this encompasses. The overarching aim of the Massey lab is, therefore, characterize the dynamics of the entire infection-to-disease process for important human pathogens by developing and applying multi-stranded functional genomics approaches.
Mission and Impact
We aim to define the processes by which major bacterial pathogens cause disease with a view to developing novel preventative and therapeutic approaches.
Our lab uses several complementary approaches to study microbial pathogenicity. In collaboration with clinical colleagues, we have access to collections of clinical isolates of both Staphylococcus aureus and Streptococcus pneumoniae with associated patient data. Using in vitro virulence phenotyping data as well as genome sequence data for the bacteria we identify novel virulence factors and virulence regulators using statistical approaches such as Genome Wide Association Studies (GWAS) and random forest modelling. The molecular detail on the contribution these novel virulence factors make to disease progression is then determined using molecular and cell based approaches.
Currently, our team is working on the following projects:
1) Characterisation of novel S. aureus toxicity affecting loci. S. aureus produces many toxin that destroys human tissue and is responsible for many severe symptoms of an infection. To understand the full genetic basis of toxin production we have applied a GWAS approach to large collections of clinical isolates and this has identified several novel toxicity affect loci with unknown function. We are currently working to characterise the activity of these protein to evaluate their potential as novel therapeutic targets.
2) Defining the genetic basis of capsule production by S. aureus. Many bacteria such as S. aureus produce a capsule to protect themselves from several aspect of the host’s immune system. Although the locus responsible for encoding the enzymes directly responsible for capsule production has been well characterised, our recent GWAS work has identified several novel capsule affecting loci associated with increased patient mortality following bacteraemia. The activity of these novel loci is under investigation.
3) Determine the genetic basis for pneumolysin production by Streptococcus pneumoniae. Pneumolysin is a toxin that causes the majority of the tissue damage associated with Strep. pneumoniae infections. By applying our GWAS approach to collections of clinical isolates we have identified novel loci that affect pneumolysin production, the activity of which are currently under investigation.
4) Defining the genetic basis of serum resistance by S. aureus. The ability of S. aureus to resist the antibacterial effect of serum contributes to the ability of this pathogen to cause invasive infections such as bacteraemia. We are currently in the process of quantify serum resistance for a large collection of clinical isolates to determine the genetic basis of this important virulence phenotype.
5) Development of novel tools for the rapid diagnosis of infections. In collaboration with industrial partners Microgenetics Ltd (https://microgenetics.co.uk/) we have been developing novel methods to rapidly detect small numbers of microorganism for use as both a sterility test and a rapid infection diagnostic.
You can find further publications on Explore Bristol Research
- Yokoyama M, Laabei M, Stevens E, Bayliss S, Ooi N, O'Neill A, Murray E, Williams P, Lubben A, Reeksting S, Pascoe B, Sheppard S, Recker M, Hurst LD and Massey RC. 2018. Epistasis mediated alleviation of the cost of antibiotic resistance for MRSA. Genome Biology. 19:94.
- Recker M, Laabei M,Toleman MS ,Reuter S ,Saunderson RB ,Blane B, Török ME, Ouadi K, Stevens E, Yokoyama M, Steventon J, Thompson L, Milne G, Bayliss S, Bacon L, Peacock SJ, Massey RC. (2017) Clonal differences in Staphylococcus aureus bacteraemia- associated mortality. Nat Microbiol. 2:1381-1388.
- Laabei M, Uhlemann AC, Lowy FD, Austin ED, Yokoyama M, Ouadi K, Feil E,Thorpe HA, Williams B, Perkins M, Peacock SJ, Clarke SR, Dordel J, Holden M, Votintseva AA, Bowden R, Crook DW, Young BC, Wilson DJ, Recker M and Massey RC. (2015) Evolutionary Trade-Offs Underlie the Multi-faceted Virulence of Staphylococcus aureus. PLoS Biol. 13(9):e1002229.
- Laabei M, Recker M, Rudkin JK, Aldeljawi M, Gulay Z, Sloan TJ,Williams P, Endres JL, Bayles KW, Fey PD, Yajjala VK, Widhelm T, Hawkins E, Lewis K, Parfett S, Scowen L, Peacock SJ, Holden M, Wilson D, Read TD, van den Elsen J, Priest NK, Feil EJ, Hurst LD, Josefsson E and Massey RC. (2014) Predicting the virulence of MRSA from Genome Sequences. Genome Res. 24:839-49. Recommended by the Faculty of 1000
- Rudkin, J.K. A.M. Edwards, M.G. Bowden, E.L. Brown, C. Pozzi, E. Waters, W. Chan, P. Williams, J. O’Gara and R.C. Massey. (2011) Methicillin resistance reduces the virulence of HA-MRSA by interfering with the agr quorum sensing system. J. Infect. Dis. 205(5):798-806.
Our lab is generously funded by the Wellcome Trust, the BBSRC and the MRC.