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  Copy number signatures in single cells as biomarkers for drug response


   Cancer Research UK Cambridge Institute

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  Prof Florian Markowetz  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

The Cancer Research UK Cambridge Institute (CRUK CI) is a joint venture between the Charity, Cancer Research UK, and the University of Cambridge. The Institute has excellent state-of-the-art facilities and research ranges from basic cancer biology and computational biology through to translational research and clinical application. Graduate students play a pivotal role in the continuing success of our research programmes and gaining a studentship in the Institute is an excellent opportunity to start a research career in an environment committed to training outstanding cancer research scientists of the future. For further information, go to: https://www.cruk.cam.ac.uk/jobs-and-studentships/postgraduate-study

Dr Florian Markowetz wishes to appoint a student to work on the project entitled: Copy number signatures in single cells as biomarkers for drug response.

For further information about the research group, including their most recent publications, please visit their website: https://www.cruk.cam.ac.uk/research-groups/markowetz-group

Project description:
The goal of this project is to overcome the genomic complexity of cancers with high chromosomal instability by using signatures of ongoing mutational processes as biomarkers for drug response. Chromosomal instability is a hallmark of most lethal cancers. Highly unstable tumours have few biomarkers to guide treatment decisions and patient survival has not improved for decades. We have pioneered approaches to dissect chromosomal instability using genome-wide DNA copy number patterns, so called CIN signatures, which are characteristic for different types of instability and underlying mutational processes (Macintyre et al, 2018). We have further developed a novel single cell DNA sequencing approach to identify ongoing mutational processes from unique events in individual cells. This pharmacogenomic test allows us to separate ongoing mutational processes, which are actively contributing to cancer development, from extinct mutational processes, which left marks in the genome but are no longer active. The student will develop a computational framework to use single cell copy number profiles as drug biomarkers and apply it to cell line and organoid data.

Qualifications/skills:
We are seeking to appoint a student with prior experience in genomic data analysis. Applicants must have computer programming skills and be familiar with data analysis in R and Python.

How to apply:
All applications need to be made using the University Applicant Portal. Please visit: https://www.graduate.study.cam.ac.uk/courses/directory/cvcrpdmsc for further information about the course and to access the applicant portal.

To complete your on-line application, you need to provide the following:

Reference Request: The names and contact details of two academic referees who have agreed to act on your behalf.

Research: If you wish to be considered for more than one studentship, please enter the names of all of the supervisors you wish to consider your application in the ’Research summary’ text box. If you only wish your application to be considered by a single supervisor, then please enter their name in the ’Research Supervisor’ text box. Please describe your past ’Research experience’ in the appropriate text box.

Course Specific Questions: Your statement of interest (limit of 2,500 characters) should explain why you wish to be considered for the studentship and which qualities and experience you will bring to the role. Please also state how you learned of the studentship.

Supporting Documents: Please upload your CV (PDF file), which should include a list of the examinations taken at undergraduate level and if possible, your examination results.




Funding Notes

Funding:
This project is funded by a Cancer Research UK studentship that includes full funding for University and College fees and a stipend of £19,000 per annum.

Eligibility:
No nationality restrictions apply to Cancer Research UK funded studentships. Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second class degree (or equivalent) in a relevant subject from any recognised university worldwide.


References

Further reading:
Copy-number signatures and mutational processes in ovarian carcinoma G. Macintyre et al. Nature Genetics, 50, 1262¿1270 (2018) PMID:30104763 ' doi:10.1038/s41588-018-0179-8 ' bioRxiv:174201