Toxicology MSc

Damaged DNA fragments stream out from a cell nucleus in a Comet assay but how can chemicals damage DNA?

The MSc is of 12 months duration commencing late September and can be take either full-time over one year or part-time over two years. It comprises six 20 credit taught modules and a 60 credit research project. There are two taught modules in both semester 1 and 2 that run in parallel and are taught on Monday-Tuesday and Thursday-Friday respectively making the course suitable for part-time students who can take one module each semester over a 2-year period:

• Metabolism and Mechanisms of Toxicity
• Forensic, Clinical and Occupational Toxicology
• Practical Skills for Toxicologists

• Assessing Toxic Potential
• Regulatory Science and Toxicology for the 21st Century
• Integrated Toxicology

Twenty credits of generic and specific training is embedded throughout the taught modules reinforcing teaching and providing a wide variety of transferable skills. A final synoptic exam encourages the development of an integrated view of the subject. During the year you will make several site visits to establishments involved in toxicological research and development. International experts from outside the university make a substantial contribution to the taught modules and the material covered is driven by the needs of industry for toxicology training.

Nanoparticles (red) surround the nucleus (blue) of a lung cancer cell — how do nanoparticles enter cells and how are they toxic?

This module describes the disposition of foreign compounds within the body of living organisms. It covers the methods used to study xenobiotic metabolism – their absorption, distribution and excretion and includes the application of molecular biology techniques to study drug metabolism of pharmacogenetics. The major metabolism pathways are discussed including phase 1, 2 and 3 reactions. The effect of species, age, sex and nutrition on these reactions is also discussed. Aspects of enzyme kinetics and pharmacokinetics are covered as are the role of receptors and cell signalling pathways. The cellular basis of cell toxicity and death are also introduced and discussed with the use of examples (e.g. reactive oxygen species). Other aspects covered include an introduction to the role of drug metabolism in the drug development process and an introduction to safety pharmacology. In addition there is a series of lectures introducing clinical toxicology where the effects of poisoning with a range of pharmaceutical drugs are discussed in detail along with aspects of their clinical management; this is taught by clinical staff from City Road Hospital.

This module introduces students to occupational and forensic toxicology (e.g. drugs of abuse) and further develops the clinical aspects of toxicology introduced in Metabolism and Mechanisms of Toxicity. Aspects of chemical poisoning and management are discussed with the use of occupationally and environmentally relevant chemicals (e.g. metals, pesticides, insecticides). Features of environmental toxicology and occupational health are also covered with specific examples of occupational carcinogens as are the role of biological monitoring and epidemiology studies and how these data are used to set effective exposure limits.

Other specialist examples such as respiratory sensitizers, immunotoxicity and skin toxicity are also reviewed. An overview of the cellular and molecular mechanisms of carcinogenesis is also discussed including aspects of cell cycle control, regulation of gap junctions and the roles of cell signalling and epigenetics.

Cells in the vicinity of this metal fragment have been destroyed by apoptosis — how and why did it happen?

This module describes the methodology for testing chemicals for toxic potential using both in vitro and in vivo techniques as well as high-throughput test systems such as cDNA microarrays, proteomics, metabolomics and transgenic animal technologies. Alternative approaches such as in silico testing are also discussed as is the limit of current in vitro approaches and the need for in vivo studies. Students will learn how to detect acute and chronic toxicity in animal studies with emphasis being placed on the pathological responses to toxic substances in different key organ systems (e.g. liver/kidney/heart/lung). They will be taught how to recognise acute and chronic inflammation, necrosis, neoplasia, hypertrophy and other cellular changes as demonstrated by histology. The choice of experimental species to demonstrate general and reproductive toxicity is also considered.

This module focuses on big data-driven science in environmental and toxicological genomics. This module will review current regulatory toxicological and risk assessment practices using the US National Research Council (NRC) publication “Toxicity-testing for the 21st Century” and the UK/EU policy guidelines as points of reference to discuss the proposed changes that incorporate 21st Century innovations in context of their scientific underpinnings, the promises they offer and challenges they present. It will draw from the fields of molecular biology, genomics, genetics, evolutionary biology, computational biology, toxicology, and risk assessment –though these are not prerequisites for enrolment. Theory and concepts will be highlighted by real world applications drawn from the scientific literature. By involving instructions from industry, government agency and NGO scientists, it means to offers a variety of dynamically evolving career paths to students.

Gene sequence analysis, but how can changes in DNA sequence explain individual responses to drugs and toxic chemicals?

This module is aimed at improving the communication, data handling, team working, essay and report writing, presentation and laboratory skills of students and is embedded throughout the other modules of the MSc Toxicology programme (5 credits per module). Students are taught to develop their communication and presentation skills which they develop independently by undertaking exercises in literature searching/information retrieval and communication of their findings in written reports. Students also learn how to design experiments and to apply statistical analysis to toxicological data. There are also more specialised IT skills training involving structure activity relationshipsand metabolism prediction, pharmacokinetics computer simulations as well as data handling workshops and practical classes.

This is a module based on student-centred learning. Students are given time to work through all the topics covered in earlier modules on their own and to raise any areas of concern with the members of staff responsible, who give additional guidance as necessary.

This takes place over 12 weeks from May to August and is an opportunity for the student to select a research topic from their area of interest. Projects can be based in the University, a research institute, a hospital, an environmental agency or in industry in this country or overseas. They can be laboratory based, computer based or literature/survey based. So a wide variety of exciting opportunities are available but in all cases students will investigate a toxicological problem in depth and write a detailed report of their findings for submission.

Collaborating organisations have included:

• Cancer Research Campaign laboratories
• the Regional Toxicology Unit
• AstraZeneca
• GlaxoSmithKline
• Unilever
• the Health Protection Agency
• the MRC Toxicology Unit
• the MRC Institute for Environment and Health
• the National Center for Toxicological research, Jefferson, USA.

There is an industry sponsored prize awarded annually for the best project dissertation

Recent project titles offered to MSc Toxicology students

• Molecular pathology of radiation‐induced mammary tumours
• Does x-ray damaged DNA persist in tissues long after their initial irradiation?
• In vitro alternatives to determine skin sensitization of agrochemical products
• Identification and characterization of novel regulators modulating programmed cell deathand tissue recovery
• Target Safety Review of PI3 Kinase Inhibition
• Cellular responses and resistance to histone deacetylase inhibitor treatment in Burkitt'sLymphoma
• Endocrine disruptors: over‐hyped or serious risk to human health?
• Phytoestrogens: beneficial or hazardous to human health?
• Analysis of phospho‐proteomic datasets from human breast cancer cells addicted to FGFRsignaling
• The role of MCL1 in Breast Cancer Cell survival
• Do supramolecular iron cylinders inhibt DNA repair
• Utility of In vitro models of the respiratory tract to replace animal models for agrochemicalsafety testing
• Indentification of novel anti‐tumour agents from marine sediments
• Characterisation of nitroreductase‐ an enzyme proposed for use in cancer gene therapy
• The cellular role(s) of the enzymes NQO1 (cytosolic NAD(P)H: quinone acceptoroxidoreductase 1) and NQO2 (NRH: quinone oxidoreductase 2)
• Bacterial Toxins: structures, mechanisms, use and abuse
• The role of Dynasore in intracellular membrane trafficking
• Cracking the code of suspended animation
• Structure‐activity and safety assessment of chloroacetanilide pesticides and theirenvironmental metabolites
• An assessment of the health effects from addition of fluroide to drinking water
• Effect of topoisomerase II inhibitors on genome stability
• Toxicity of novel ferrocene analogues
• ZnO nanoparticle mediated toxicity and perturbation of algae‐Daphnia kairomone signalling
• Optimisation and validation of a high‐throughput imaging system for Daphnia toxicity tests;automating the measure of key phenotypic endpoints for use in environmental riskassessment (ERA) and in the context of adverse outcome pathways (AOPs).
• Crystallographic structure determination of E. coli nitroreductases.
• Epigenetics effects of vitamin B12 in clones
• Epigenetic key players in sex determination for toxicological model organism