There is overwhelming evidence that inherited mutational changes in humans are responsible for genetically determined diseases and congenital (heritable) malformations. In addition, the accumulation of somatic cell mutations is known to be implicated in cancer, and to some extent in other multi-factorial diseases. As novel drugs may represent a potential source of damage to DNA, appropriate testing is required to minimise the risk of genotoxicity for both ethical and legislative reasons. The discipline of genetic toxicology as applied to drug development exists to achieve this aim.
The minimum genotoxicity package consists of (a) an in vitro bacterial assay for gene mutation, (b) an in vitro mammalian cell assay for gene mutation and/or cytogenetic damage, and (c) an in vivo mammalian assay for cytogenetic damage. A negative result in all three assays is usually sufficient to provide evidence for a lack of genotoxic potential. Compounds in early development maybe tested in “cut down” versions of the standard assays to assist with candidate selection and development prioritisation. Additional testing may be required for substances with structural chemical alerts, or when there is evidence of the carcinogenicity of structurally similar compounds.
More testing is also needed if one or more of the standard or candidate selection assays produces a positive result. Such investigations are often used to provide mechanism based risk assessments e.g. for compounds that induce chromosome loss (aneugens) a threshold based argument may be used for risk assessment based on safe margins of exposure in the patient population. As such, the genetic toxicology unit undertakes a variety of research projects to evaluate innovative technologies or to investigate issues associated with the risk assessment of genetic damage.
Students undertaking a placement in genetic toxicology will perform investigative studies associated with the work of the dept. This will undertake the form of a research project to consist of literature review and the establishment of expertise in one or more of the following technologies: flow cytometry, bacterial and mammalian cell/tissue culture, microscopy and image analysis. Following appropriate training, students will be expected to conduct independent research and collate and analyse experimental data, write reports/summaries and a dissertation at the end of year. They will also be expected to present the results of their work at the annual students review and external meetings, if appropriate.
The Assessment Centre for successful applicants: Expected to take place in 2020.
Degree Requirements: Must be on track for a 2.2 (or above). Ideally, you will be currently studying for a degree in Genetics including a module on Genetic Toxicology.
You will have completed a minimum of 2 years of your undergraduate degree, but will not have graduated at the start of your placement. You will be expected to provide evidence from your university to show you will be an undergraduate student for the duration of the placement year.
In addition, working alongside highly experienced genetic toxicology experts, students will develop knowledge of the drug development process and the role of safety assessment and genetic toxicology; be involved in general laboratory management duties throughout the year to gain valuable experience in the daily workings of an industrial genetic toxicology lab to directly support the screening of potential new medicines; develop scientific, IT and other core skills.
We recruit on an on-going basis and prioritise applications based on the application date. Applications will closed when we have filled our assessment centre dates. If you have what we’re looking for apply today!
This opportunity has the following recruitment stages you must successfully pass to be offered a placement year with GSK for 2020!