About me:

Charles is an internationally leading environmental biologist and (eco)toxicologist with over 40 years of research and project management experience. His research spans investigations into the mechanisms of endocrine disrupting chemicals and nanoparticle ecotoxicology to assessing population level effects of environmental contaminants in wildlife, principally fish. Much of his research includes applying genetic and genomic techniques to understand the basis of physiological processes and the mechanisms through which they are disrupted by environmental contaminants.

Charles has had many leading academic roles at Exeter including as Director of Research and Deputy Head of Biosciences and Academic Lead of the College of Life and Environmental Sciences. He is co-director for the centre for Sustainable Aquaculture Futures (a partnership with Cefas), two NERC DTP training programmes (FRESH and ECORISC) and has been the UK-coordinator and Chief Science advisor for the Defra-Japan Ministry of Environment including the UK-Japan partnership for studies on Endocrine Disrupting Chemicals for over 15 years. Charles has been awarded various international prizes including the Fisheries Society of the British Isles Beverton Medal for Outstanding research in fish/ fisheries, the Founders Award (Society of Environmental Toxicology and Chemistry) the highest global award offered by SETAC to an individual with an outstanding career in the environmental sciences, and the Marsh Award for Marine and Freshwater Conservation Founders Award (Zoological Society of London) in recognition of an outstanding contributions to environmental ecotoxicology and aquatic animal health.

Interests:

Endocrine Disruption: A major focus of my research interest is endocrine disruption, the study of chemicals that alter hormone function which can lead to adverse impacts on health. Our work with colleagues at Brunel University was some of the very first research to show that effluents from wastewater treatment works causes feminisation of male fish. My teams work has subsequently proven that feminisation of wild roach living in UK rivers is caused by exposure to treated sewage effluents. Using a targeted biological screening of chemically fractionated bile from effluent exposed fish, with collaborators (University of Sussex), we have been able to identify the suite of feminising chemicals in effluent discharges, principally environmental oestrogens, and through laboratory exposures proven they contribute to the feminisation of wild fish in UK rivers. These chemicals include natural and synthetic steroid oestrogens, and alkylphenolic compounds. This original work has been very highly cited. Combining empirical studies with models including Concentration Addition/Joint Independent Action, my team has further established that oestrogenic chemicals can be additive in their effects and these findings have had a widespread and international influence. More recently we discovered the widespread presence of anti-androgenic chemicals in wastewater effluent discharges and my team is now studying their possible contribution to the feminisation of fish living in UK rivers.

A major question we are now trying to establish is whether wild fish (roach, Rutilus rutilus) populations are impacted adversely by exposure to oestrogenic effluent discharges. Undertaking controlled breeding studies in the laboratory and applying DNA microsatellites to assess parentage with have proven that moderately to severely feminised males have a reduced capacity to compete with normal males to sire offspring. We have further shown that life long exposure to an oestrogenic effluent (at full strength) causes complete gonadal feminisation of males, some of which were able to breed as females. In some of our most current work we are applying DNA microsatellites to establish whether roach populations living in rivers heavily polluted with wastewater effluents have a reduced effective population breeding size. If so, this will show that exposure to wastewater effluents at these sites is fundamentally affecting population genetics.

The mechanisms of action and pathways of effects have been established for very few endocrine active chemicals and this has been another key focus of my teams work. Targeted single gene approaches, gene arrays and more recently sequencing technologies have been applied to unravel some of the molecular mechanisms of oestrogenic disruption (including for mixture effects) and other forms of chemical toxicity. Other ongoing projects include studying the metabolome and xenometabolome in fish in response to exposure to effluents and individual EDCs with Profs Hill (University of Susses) and Prof Viant (University of Birmingham). Most recently, working with Dr Kudoh, also at Exeter, we have developed a ERE-GFP transgenic zebrafish that is exquisitely sensitive to oestrogens that allows us to identify – through the expression of a green fluorescent protein - where different oestrogens interact in the body and in real time. This is a very power tool that we are now using to investigate the potential for wider health impacts of exposure to environmental, oestrogens. We are currently attempting to develop a similar model for (anti-) androgens. Members of my team also work on other chemical contaminants of environmental and human health concern including pesticides and pharmaceuticals.

I have an interest also in the development and application of in vitro systems for understanding mechanisms of action and reducing animal use. These systems include cell culture (especially hepatocytes), recombinant cell lines and receptor transactivation assays.

Almost all of our work on endocrine disruption is focused on fish, but we have also worked on birds (Dipper, Cinclus cinclus), mammals (Otter, Lutra lutra) and various invertebrates.

Nanotoxicology: Nanotechnology is an emerging field of science that deals with engineered molecules of an extremely small size (1-100 nanometres). Because of size – related changes in physico – chemical properties, substances at the nanoscale display optical, magnetic and chemical properties that can differ greatly from the standard material enabling diverse commercial applications. Nanoparticles are currently used in products such as suntan lotion, cosmetics, clothing, cleaning materials, medicines and food and assessing the potential health risks associated with exposure to nanoparticles is now recognised as being a major international research priority. Working with other members of the Envrionment and Evolution theme (Prof Galloway) my team is researching into the effects of metal and metal oxide nanoparticles, principally in fish, but also some invertebrates.

Most of our research on nanomaterials has been focused on understanding their bioavailability, including for exposures in natural waters and in effluents. This work is being complemented by in vitro studies with various fish cell types including hepatocytes, gut and gill cells to investigate how nanoparticles cross cell membranes and their fate within cells. Further methods applied in this work include whole mount in situ hybridisation to investigate specific gene responses in the bodies of whole embryos. Various analytical techniques and state of the art imaging techniques are being employed to monitor particle fate and behaviour in the water and fish, including RAMAN scattering. In our work to date we have found that many metal nanomaterials ( ceria, zinc, titania) show little toxicity to fish. In contrast silver nanoparticles are toxic, albeit that this toxicity may result from dissolution and free silver, rather than an innate function of the particles themselves. In our current work we are applying whole genome sequencing on exposed zebrafish embryos and the target tissues for specific nanomaterials in larger fish to further establish the effect mechanisms of metal/metal oxide nanoparticles in the body and thus help unravel some of the possible health concerns linked with these materials. This work is funded by very diverse sources including Research Councils, DEFRA, and various industries reflecting the multi-stakeholder interest.

Disease: I have a growing interest in the effects of combined environmental stressors on wildlife, including features of climate change. A project that has recently been initiated with the Centre for Environment, Fisheries and Aquaculture Science is the application of sequencing technologies to understand the pathogenic process of white spot virus, a major disease organism for cultures and wild crustaceans.

Basic Biology: Underpinning all of my teams ecotoxicology work is my interest in the basic biology of fish and other wildlife species. Here primary interests include understanding the mechanisms controlling sexual development and reproduction. To be able to assess what is abnormal for exposure to an environmental stressor, it is important to understand the normal basic processes and variation.

Major research activities and findings from my team include the following:

Sexual differentiation: My team has established the timing and mapped histologically the process of sexual differentiation in the roach, Rutilus rutilus, a sentinel species for studies on chemical effects in wild fish in UK freshwaters, and in the fathead minnow and zebrafish, both key laboratory species. They have further identified some of the molecular mechanisms controlling sexual differentiation in these fish.

Oogenesis (egg development) and Spermatogenesis: We have mapped histologically the process of oogenesis and spermatogenesis in roach, fathead minnow and zebrafish. In this work we have especially focused on the process of vitellogenesis (provision and uptake of yolk into oocytes) and established some of the endocrine and molecular mechanisms controlling yolk uptake and processing. Our work has included the cloning and sequencing of the first cDNA for a fish vitellogenin receptor, establishing the developmental expression and cellular localisation of the vitellogenin receptor mRNA in fish oocytes, and the cloning and sequencing of some of the first yolk processing enzymes (cathepsins) in oocytes. My team has also developed some of the first assays to quantify vitellogenins in fish, which have been vital for work on endocrine disruption.

Endocrine control of fecundity: Very little is known about the determinants of fecundity in any animal. Fish, because they are highly fecund, provide excellent model systems for investigating the endocrine control of oocyte recruitment and growth - the associated titres of plasma hormones are considerably higher than for most other animals. Applying the technique of unilateral ovariectomy (to manipulate oocyte recruitment) we have identified some of the hormones controlling ovarian development.

Puberty: We have cloned the KiSS I receptor in various fish species, identified and cloned some of the KiSS peptin ligands (the first to do so in fish) and mapped them to their chromosomes. We have established the ontogeny and localization of expression of KiSS 1 receptor in the brain in both male and female fathead minnow during sexual development and shown how this expression aligns with the expression of an extensive suite if other genes involved in mediating sexual development (e.g. the GnRHs). The ability to control puberty in fish would be of great significance in the aquaculture of many fish species.

Sexual behaviour: The zebrafish is one of the major models for studies in ecotoxicology, yet very little is known about its basic biology. My lab team has contributed to filling this knowledge gap through extensive studies on its reproductive biology. In this work we have projects studying the behaviour of the zebrafish in breeding colonies. This work is principally focused on understanding the interactions and hierarchies that develop in zebrafish colonies to advance our understanding on their breeding dynamics in natural populations. In this work, detailed studies on male-male, male-female and female-female interactions are being established for different sized colonies and the reproductive success of individuals in those colonies are determined through genotyping of the offspring produced (through the use of DNA microsatellites). Our work on zebrafish is principally laboratory based, but we also have some ongoing studies on natural colonies in Bangladesh. This work also includes the development and application of population models.

New Models: I am always interested in exploring new models for understanding basic reproductive processes and/or exploiting them for better understanding possible health effects of environmental contaminants. A model we are currently working on is a Xenotoca spp, that gives birth to live young. Currently we are studying the basic reproductive biology, but our longer term plan is o use this model to investigate maternal transfer of EDCs, pharmaceuticals and nanomaterials and their health effects on developing embryos.

Wildlife Biology. My passion in life is wildlife and I have a series of projects with various external partners including the UK Environment Agency, defra, cefas, RSPB, BTO, Dartmoor National Park studying the ecology of various insects and birds(most notably the Cuckoo).

Current Funding

• 2010 -2013 Joint US-UK (NERC) Research Program: Environmental Behaviour, Bioavailability and Effects of Manufactured Nanomaterials (EPA-G2008-STAR-R1) - (£203 000 PI to Exeter, PI., total grant £3M). Consortium for Manufactured Nanomaterial Bioavailability & Environmental Exposure (nanoBEE).
• 2010 -2013 EU - Qnano. Infrastructure and toxicology assessment unit. (Euros 285 991, Co-I)
• 2010 Wolfson. Zebrafish Developmental Biology Imaging Unit (infrastructure and microscopes) (£400k PI).
• 2011-2013 DEFRA (£160 000 - PI). Emerging endocrine disrupting chemicals. UK/Japan partnership Grant. Pending
• 2011-2014 NERC(£420 000 - Development and Application of Transgenic Biosensor Zebrafish
  for Assessing the Environmental Health Impacts of Anti-Androgens.
• 2011 CEFAS (£17 000 –co PI). Investigating the potential molecular mechanisms associated with white spot virus resistance in Carcinus maenas
• 2011-2014 CEFAS (£37 500 - co I). The Implications of Ocean Acidification in Combination with Chemical Stressors for Juvenile Fish (50% PhD studentship support)
• 2011-2014 Leverhulme (£143 800 - co I). The Evolution of Cooperation in Structured Animal Societies
• 2011-2014 Interegg European Neurosciences Project (Euros140 00 –PI).
• 2012 DEFRA/ Open Innovation Fund. (£60 000 - co I) CB0456 - Global NanoMaPPP - Ecotoxicology of
  Metal Oxide Nanomaterials in the Aquatic Environment
• 2012-2015 Cefas- (£300k, drawing down further support from the UoE Open Innovation platform - value of total grant £532 000, PI). Building a Molecular Platform for Understanding the Host-Pathogen Interface in Invertebrates.
• 2012-15 EU (£300k, co-I). ( CLEANSEAS) . Microplastics in the Marine Environment
• 2012 British Ecological Survey (£1,860 - PI): Niche partitioning and factors determining success of ground nesting birds, including Cuckoo parasitism, on Dartmoor
• 2012-15 EU. (540k Euros, PI). NanoMILE (10 million Euro Consortium grant). Nanoparticles in the Environment.
• 2013 Cefas. (£28,854 PI). Exposure effects of natural plants extracts on fish
• 2013-15 BASF (£144 000, co-I with Prof Galloway). Ecotoxicology of nanopolymer dispersions. A case study of aqueous acrylic ester copolymers.
• 2013-14 Spanish Government (£30 000 co-I)Molecular identification of sex, reproductive stage and fecundity in fish of commercial interest: mechanisms, aplications and exploitation. SEXOVUM.
• 2013-14 NERC (FENAC/2012/11/002; £24 000 co-I). Transfer of Bulk and Nanoparticulate Cerium between a Mussel and a Crab
• 2013-14 NERC (FENAC/2012/11/001; £24 000 P.I). Biological uptake and effects of metal oxide nanomaterials in early life stages of fish and for exposure to a complex mixture
• 2013-16 NERC (£578 000 P.I., £399 000 to Exeter). Can roach, Rutilus rutilus, adapt to the harmful effects of oestrogen exposure from waste water treatment work effluents?
• 2013-16 German Gov. (40 000 Euros P.I). Consultant for the German National programme on Nanomaterials
• 2013-15 BBSRC (£149,724, PI) Exploiting Transgenic Zebrafish Embryos/Larvae for Systems- Wide Analysis of Endocrine Disrupting Chemicals
• 2013-14 Defra ((£64 000)Predicting Reproductive Failure in Frogs using Non-destructive Biomarkers – A Pilot Study
• 2013-15 NERC/TSB/KTP –Develop and Validate Numerical Modelling Capability for HR Wallingford - (£247 870 co-I)
• 2013-16 EU (€139,600 Co-I, total consortium €6million) GuideNano: Assessment and mitigation of nano-enabled product risks on human and environmental health

Qualifications:

2003 DSc University of Lancaster
1984-1987 PhD University of Aston
1983-1984 MSc in Applied Fish Biology, University of Plymouth
1980-1983 BSc (Hons) Biological Sciences, University of Lancaster

Career:

2010-2015 Chief Science Advisor for United Kingdom-Japan Research into Endocrine Disruption, Department of Food and Rural Affairs
2010-present Deputy Head Biosciences, Academic Lead College of Life and Environmental Sciences
2005-2010 Director of Research for Biosciences, University of Exeter
2005-2010 UK Supervisor for United Kingdom-Japan Research into Endocrine Disruption, Department of Food and Rural Affairs
2005-2008 Honorary Research Fellow of the Institute of Zoology, London
2000-present Professor in Environmental and Molecular Fish Biology, University of Exeter
1999-2000 Reader in Biological Sciences, Brunel University
1996-1999 Senior Lecturer in Biological Sciences, Brunel University
1990-1996 Lecturer in Biological Sciences, Brunel University

Honours/Awards

2012 Elected Fellow for the Society of Biology
2012 The Fisheries Society of the British Isles Beverton Medal for ground breaking research in fish biology
2011 University of Exeter Impact Award for Outstanding contribution to Policy and Public Services
2008-to date Honorary Chair, Peninsular College for Medicine and Dentistry
2005-to date Honorary Research Fellow of the Institute of Zoology, London