We are seeking a highly motivated PhD student to join our new research group at the MRC Toxicology Unit at the University of Cambridge. She/he will work on an experimental and/or computational biology project to understand the mechanisms underlying liver toxicity and disease.
Liver disease usually develops in the context of chronic cellular injury caused by exogenous insults, including drugs and environmental exposures [1]. The incidence of liver disease is rapidly increasing in the UK and other developed countries due to rising alcohol consumption and an epidemic of type 2 diabetes leading to non-alcoholic fatty liver disease (NAFLD). This is a research area of substantial unmet needs in prevention, detection, and treatment, and the MRC Toxicology Unit offers the ideal environment to pursue this research.
We recently discovered lesion segregation [2], which occurs when DNA lesions persist though cell division and can generate multiallelic and combinatorial genetic diversity. Lesion segregation can be caused by exogenous mutagens [3] such as chemotherapeutics, and is a unifying property of mutagens in human cells and tumours.
The aim of this PhD project is to study the persistence of lesions caused by different DNA damaging agents, including existing and novel therapeutics, and explore the molecular and genomic consequences for cellular phenotypes. This work will advance our study of how the liver responds at a molecular level to exogenous insults. The recruited candidate will use a combination of molecular biology, experimental pathology, and image analysis approaches to address these problems with the overall goal of gaining a mechanistic understanding of the direct links between exposure/injury and disease outcomes, including cancer.
The successful candidate will gain experience in a breadth of experimental and analytical techniques, including molecular biology, cell culture, drug assays, high-throughput sequencing, and statistical data analyses. She/he should have strong analytical skills, in addition to creativity, curiosity, enthusiasm, and the ability to work in a team.
Candidates must expect to obtain qualifications at the level of a first-class or 2.1 Honours Degree in a related discipline and must be enthusiastic to collaborate closely with other members of the team.
References
1. Brunner, S. F. et al. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature 574, 538–542 (2019).
2. Aitken, S. J. et al. Pervasive lesion segregation shapes cancer genome evolution. Nature 583, 265–270 (2020).
3. Connor, F., Rayner T., Aitken, S. J. et al. Mutational landscape of a chemically-induced mouse model of liver cancer. J. Hepatol. 69, 840–850 (2018).
Find out more about us here: http://www.aitkenlab.org
Formal applications should be sent to https://www.postgraduate.study.cam.ac.uk/courses/directory/bltopdtox/apply