School of Biosciences

Research Interest Areas

The LPRG specialises in ‘Molecular Environmental Health’, with a research focus on the “determination of intelligent biomarkers of exposure and harm” in the respiratory system following exposure to aerial xenobiotics (Figure 1).

Figure 1. Scanning electron microscopy image of combustion-derived soot particles deposited in the bronchial epithelium. Note the abundance of cillia covering the surface of the epithelium.  The presence of red blood cells denotes tissue injury.

The aerosols may be derived from anthropogenic (man-made; combustion-derived, cosmetics and pharmaceuticals), biogenic (biological; pollen, fungal spores and insect detritus), technogenic sources (industry; smelter and coal fly-ash) and geogenic (natural; volcanic ash and eroded earth minerals) (Figure 2) sources.

Figure 2. Scanning electron microscopy image of the different sources of ambient particulate pollution (e.g. PM10; particulate matter 10 microns or less). Note the heterogeneity of particle types in a typical urban PM10 sample. 

Conducting research in this highly complex inter-disciplinary topic requires a structured coordination of expertise and contributions from various scientific disciplines including Chemistry, Physics, Biology, Medicine and Engineering. Understanding “mechanisms of human health effects caused by ambient aerosols” requires knowledge of the differential particle and gas phase effects. State-of-the-art technologies for comprehensive molecular characterisation of both the biological responses and the exposure characteristics are applied together with chemo-metric and bio-statistical analyses to achieve a ‘holistic approach’ towards inhalation toxicology (Figure 3).

Figure 3. Flow chart of steps involved in the holistic approach to particle toxicology and discovery of biomarkers of exposure and harm in the respiratory system.

Biomarkers (e.g. physical, chemical, inter-omic) of exposure and harm to indoor and outdoor air pollutants are identified using advanced in vitro aerosol exposure systems. Innovative human tissue-engineered equivalent models of the respiratory epithelia are employed to bridge the gap between the observed human health effects and air pollution-dependent lung injury and disease (Figure 4).

Figure 4. Schematic diagram for recapitulation of a human lung construct from medical waste tissue derived from the bronchial epithelium (i.e. proximal lung compartment).

Biological responses, which can subsequently lead to health effects and diseases, are observed after exposure to aerosols, with reactive oxygen species (ROS) and reactive organic components (ROC) in the particulate and gas phases, along with their synergistic effects, the focal points of our investigations that encompass the following research aims:

• Identification and quantification of ROS in relevant aerosol sources (e.g. traffic, wood combustion, incense burning, coal fly ash, cooking fumes, pharmaceuticals, cigarette smoke, cosmetics etc.); characterisation of the gas/particle partition of ROC
• Development of in vitro ROS bio-assay (acellular/cellular) test systems for studies of effects induced by aerosol exposure
• Exposure of these test systems to fresh aerosol emissions and aged aerosols from relevant sources
• Differentiation between impact of the total aerosol and impact of the particulate phase and the gas phase
• Analytical methods for comprehensive profiling of small molecules in biological systems and aerosol exposure
• Toxicological characterisation and comprehensive response analysis at different hierarchical inter-omic levels (e.g. transcriptom, proteom, metabolom) of the biological test systems, in order to reveal exposure dependent alterations
• Integrated chemo-metric and bio-statistical analysis of the data.

Current Grants Awarded

BBSRC-CASE PhD Studentship

NERC-QUOTA PhD Studentship

Unilever, UK

Institute for Science and Health, USA

Wales Waste & Resources Research Centre

Science Research Investment Fund 2

The Royal Society

UK/China & Technology Research Fund

Chinese National Natural Science Foundation

Collaborations

Dr Timothy Jones ( School of Earth, Ocean & Planetary Sciences, Cardiff University)

Dr Teresa Tetley (National Heart and Lung Institute, Imperial College London)

Prof. Ian Matthews (Department of Epidemiology, University College of Medicine, Cardiff University)

Prof. Shao Long-yi (Chinese Universiy of Moning & Technology, Beijing, China)

Prof. Brooke Mossman (Department of Pathology, University of Vermont, USA)

Dr Teresa Moreno (Instituto de Ciencias de la Tierra "Jaume Almera")

Affiliated Staff

Keith Sexton, Laboratory Manager

Dominique Balharry, Post-doctoral Research Assistant

Emma Paris, Post-doctoral Research Assistant

Lata Koshy, PhD Student

Tracy Hughes, PhD Student

Zoe Prytherch, PhD Student

Anna Wlodarcyk, MSc Student

Gaja Ramanathan, MSc Student

Robert Arthur, Post-doctoral Research Assistant

Research Accolades

• In March 2006, research on the “in vitro toxicogenomics of xenobiotics” was recognised with a Scientific Merit Award from the Institute For Science & Health (USA)
• Dr BéruBé was the British Toxicological Society Ambassador for 2006 to Australasia, to speak on the topic of “nanotoxicology”
  
• In March 2007, the NC3Rs Parliamentary Event “Replacement Prize” was won by her work on 3-D cell cultures of lung to find a possible alternative to animal testing in the field of inhalation toxicology
  
• In collaboration with Unilever, UK, she was awarded the “Science & Technology Innovation Award 2007” from Cardiff University for her human tissue equivalent lung model
• Cardiff University has now nominated Dr BéruBé. for a 2007 Bioscience Federation Science Communication Award (results pending) for her commitment to “science communication”