PhD Studentship: Error-corrected Sequencing of Carcinogenic Nitrosamines in a Human Liver Spheroid Model

AstraZeneca-Funded Non-Clinical PhD Studentship

Applications are invited for 3.5 years PhD studentship based within the MRC Toxicology Unit, University of Cambridge, with extended industry experience at AstraZeneca (Cambridge, UK). The student will be working on a collaborative project jointly supervised by Dr Sarah Aitken (MRC Toxicology Unit, University of Cambridge) and Dr Anne Ashford (Genetic Toxicology, AstraZeneca).

We are seeking a highly motivated individual to undertake a combined experimental/computational project on drug-induced genotoxicity using human models.

This is a mixed wet/dry lab project combining human liver models and sequencing. The purpose of the studentship is to apply NGS approaches to (i) understand mechanisms of nitrosamine-induced mutagenesis and (ii) advance the scientific understanding of carcinogenic risks associated with the exposure to nitrosamine impurities.

This studentship offers a unique training opportunity for engagement with leading academic and industry partners to change the current perception of the carcinogenic risk associated with nitrosamine impurities in drug products. Rotating between laboratories at the University of Cambridge and AstraZeneca the student will gain experience in a breadth of experimental and analytical techniques, including: molecular biology, cell culture, drug assays, error-corrected DNA sequencing, and statistical data analyses.

Applicants should have or shortly expect to obtain a first or good upper second-class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject such as Biomedical Science. Strong analytical skills, in addition to creativity, curiosity, enthusiasm, and the ability to work in a team are essential.

This studentship is open to UK citizens or overseas students who meet the UK residency requirements (home fees) or are able to augment the funds to cover the extra costs associated with international student fees. Full details of the University’s entrance requirements are specified here: http://www.graduate.study.cam.ac.uk/application-process/entry-requirements .

REFERENCES:

1. Thresher, Andrew, et al. “Are all nitrosamines concerning? A review of mutagenicity and carcinogenicity data.” Regulatory Toxicology and Pharmacology 116 (2020): 104749.

https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impurities-medications

https://www.ema.europa.eu/en/documents/report/lessons-learnt-presence-n-nitrosamine-impurities-sartan-medicines_en.pdf

2. Abascal, F, Harvey, LMR, Mitchell, E, et al. Somatic mutation landscapes at single-molecule resolution. Nature 593, 405–410 (2021). https://doi.org/10.1038/s41586-021-03477-4

3. Wang Y, Mittelstaedt RA, Wynne R, et al. Genetic toxicity testing using human in vitro organotypic airway cultures: Assessing DNA damage with the CometChip and mutagenesis by Duplex Sequencing. Environ Mol Mutagen. 2021 Jun; 62(5): 306–318. https://doi.org/10.1002/em.22444

4. Aitken, SJ, Anderson, CJ, Connor, F, et al. Pervasive lesion segregation shapes cancer genome evolution. Nature 583, 265–270 (2020). https://doi.org/10.1038/s41586-020-2435-1

5. Anderson, CJ, Talmane, L, … Aitken, SJ, Taylor, MS. Strand-resolved mutagenicity of DNA damage and repair. bioRxiv 2022.06.10.495644; bioRxiv 2022.06.10.495644; doi: https://doi.org/10.1101/2022.06.10.495644

Application Process

Information regarding the application process can be found at: PhD Programme MRC Toxicology Unit (cam.ac.uk)

All formal applications will need to be made through the University Application Portal:
PhD in Biological Science (MRC Toxicology Unit) Postgraduate Admissions (cam.ac.uk)

Your online application must include:

• A CV, including full details of all University course grades to date –
• Contact details for two academic or professional referees
• A personal statement of interest

Funding

Full funding covering Maintenance and the University Composition Fee (Home Fee rate) and is provided for the studentship, with effect from 1 October 2023.

Maintenance fee is £19,500 in year 1, £20,100 in year 2, £20,700 in year 3 and £21,350 in year 4.