This sandwich placement will be based in the Metabolomics STP & Cancer Evolution and Genome Instability Lab supervised by James MacRae and Charlie Swanton.
Project background and description
The TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a translational research study aimed at transforming our understanding of cancer evolution and taking a practical step towards precision medicine.
This project aims to analyse the plasma metabolite, phospholipid, and hormone profiles of TRACERx patients using a broad range of cutting-edge instrumentation, including liquid chromatography- and gas chromatography-mass spectrometry (LC-MS and GC-MS), and Nuclear Magnetic Resonance (NMR).
Preliminary analyses derived from baseline plasma in a cohort of 88 patients demonstrated in those who subsequently developed recurrent disease an increased concentration of several metabolites. This sandwich placement project will explore this further using the complete patient cohort (780+ patients), including addition of longitudinal samples collected at relapse and prior to death to track the dynamics of the plasma metabolome.
Data generated will be used to answer the following questions:
- Are there metabolic features associated with metastatic disease that predict a poor outcome (i.e. death) and that could potentially be therapeutically targeted?
- Are there plasma-derived metabolic mediators associated with a particular tumour genotype and host phenotype (e.g. altered body composition)? Can these mediators act as diagnostic biomarkers and/or be therapeutically targeted?
The results derived from this study have the potential to inform the way in which we manage patients with lung cancer, in particular the frequency of follow up and choice of therapy.
Metabolomics: The student will learn the key techniques of metabolomics and lipidomics, including powerful mass spectrometry and other analytical techniques that are widely applicable to many areas of biochemistry and cell biology.
Data analysis: The student will learn techniques for analysing cohort metabolomics datasets. From quality control, through multivariate analyses and significance testing, to deeper statistics and cross-comparison with other datasets, this studentship will provide the successful candidate with a broad toolkit of easily transferable skills.
Candidate background
The post holder should embody and demonstrate the Crick ethos and ways of working: bold, open and collegial. The candidate must be registered at a UK Higher Education Institution, studying in the UK and must have completed a minimum of two years’ undergraduate study in a relevant discipline, and on track to receive a final degree grade of 2:1 or 1. In addition, they should be able demonstrate the following experience and key competencies:
- Must be pursuing a degree in biomedical studies, biochemistry, analytical chemistry, or similar relevant field
- Good knowledge in relevant scientific area(s)
- Good written and spoken communication skills
- Ability to work independently and also capable of interacting within a group
References
1. Abbosh, C., Frankell, A.M., Harrison, T., Kisistok, J., Garnett, A., Johnson, L., . . . Swanton, C. (2023)
Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.
Nature 616: 553-562. PubMed abstract
2. Greenwood, D.J., Dos Santos, M.S., Huang, S., Russell, M.R.G., Collinson, L.M., MacRae, J.I., . . . Gutierrez, M.G. (2019)
Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages.
Science 364: 1279-1282. PubMed abstract
