PhD Studentship: Investigating the causes and consequences of R-loop dysregulation in cancer
Supervisor: Dr Magdalena Crossley
Department/location: Cancer Research UK Cambridge Institute (CRUK CI)
Course start date: 1st October 2025
Overview
Dr Magdalena Crossley wishes to recruit a PhD student to work on the project entitled: 'Investigating the causes and consequences of R-loop dysregulation in cancer'.
For further information about CRUK CI's newest research group, please visit our website at: https://www.cruk.cam.ac.uk/research-groups/crossley-group/
Project details
RNA-DNA hybrid structures, including R-loops, form on the genome and have physiological roles in regulating gene expression. However, dysregulation of R-loops can threaten genome maintenance and has been linked to cancer, neurodegeneration and autoimmunity. We investigate, at the molecular level, how R-loops and RNA-DNA hybrids become pathological, impacting genome stability and innate immunity.
We recently discovered that dysregulation of R-loop metabolism by cancer-associated mutations leads to the excision of R-loops. Excised RNA-DNA hybrids are exported from the nucleus and build up in the cytoplasm of cells, activating an innate immune response (Crossley et al., Nature 2023). We developed new biochemical, genomics and imaging approaches to study RNA-DNA hybrids across different cellular compartments. PhD projects are expected to gain mechanistic and translational insights into this novel and fascinating population of nucleic acids. Projects will be tailored to the successful individual(s) based on interests and previous experience, incorporating one or more of the following areas:
- Genome biology and cellular dynamics of RNA-DNA hybrids, eg their biogenesis from oncogene activation, retroelements and mitochondria.
- RNA-DNA hybrids in innate immunity and cellular responses, eg senescence.
- Extracellular RNA-DNA hybrid release.
- Developing genomics and computational approaches for interrogation of RNA-DNA hybrids in cells and patient samples.
Your project will explore the role of RNA-DNA hybrids in human cells, with the aim to translate our mechanistic findings into patient samples and inform new therapeutic entry points.
You can expect to develop innovative skills in both experimental and computational approaches, benefit from close mentoring, and have an opportunity to shape the scientific direction of a new research group.
Further reading
- Crossley M. P., et al. Nature (2023). doi: 10.1038/s41586-024-07064-1
- Crossley M. P., et al. JCB (2021). doi: 10.1083/jcb.202101092
- Crossley M. P., et al. NAR (2020). doi: 10.1093/nar/gkaa500
- Crossley M. P., et al. Mol. Cell (2019). doi: 10.1016/j.molcel.2019.01.024
Preferred skills/knowledge
We are looking for candidates with excellent laboratory and/or computational skills, a strong background in biochemistry, molecular biology, genomics or computational biology/bioinformatics, as well as a keen interest in RNA/genome biology. Successful candidates are expected to have excellent communication, organisational and time-management skills, an inquisitive mind, and be highly motivated to drive an independent research project.
Funding
This four-year studentship is funded by Cancer Research UK Cambridge Institute. It includes full funding for University fees and, in addition, a stipend currently of £21,000 per annum for four years.
Eligibility
We welcome applications from both UK and overseas students. 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.
Deadline
The closing date for applications is 24th March 2025 with in-person interviews expected to take place in April/May 2025.
How to apply
Please apply via the University Applicant Portal. For further information about the course and to access the Applicant Portal, visit:
https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcrpdmsc
You should select to commence study in Michaelmas Term 2025 (October 2025).
Additional information
To complete your online application, you will need to answer/provide the following:
- Choice of project and supervisor:
Please ensure that you name the project (with reference code) and Dr Madzia Crossley as supervisor, where indicated.
- Course-specific questions
(a) You will be asked to give details of your Research Experience (up to 2,500 characters)
(b) Your Statement of Interest (up to 2,500 characters) should explain why you wish to be considered for the studentship and what qualities and experience you will bring to the role.
- Supporting documents
Applicants will be asked to provide:
(a) Academic transcripts
(b) Evidence of competence in English (if appropriate)
(c) Details of two academic referees
(d) CV/resume
Please quote reference SW45073 on your application and in any correspondence about this vacancy.
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.
The University has a responsibility to ensure that all employees are eligible to live and work in the UK.
PhD positions to study precision medicine for respiratory diseases
Asthma and COPD are widespread chronic respiratory diseases that impose a heavy social and economic burden. Traditional treatments often follow a "one-size-fits-all" approach, merely suppressing symptoms without achieving true health improvements. The MSCA Doctoral Network RESPIRE-EXCEL is set to revolutionize this by introducing precision medicine tailored to individual patients. We are looking for 15 enthusiastic PhD students to join our innovative project. As a PhD student in RESPIRE-EXCEL, you will be part of a dynamic, international team of young researchers. You will undertake your own research project at your host organization, focusing on your specific area of interest. To broaden your expertise, part of your PhD will be conducted at other RESPIRE-EXCEL partner organizations via internships.
Our program offers advanced interdisciplinary courses led by top experts in Precision Medicine for Respiratory Diseases. You will gain cross-sectoral competencies and multidisciplinary knowledge, enabling you to collaborate effectively with industry, healthcare, and academia. The RESPIRE-EXCEL consortium includes numerous academic, industrial, and societal partners from across Europe and the UK, such as the European Lung Foundation and the European Respiratory Society. Are you ready to make a difference in the field of respiratory medicine? Explore the PhD positions available in the RESPIRE-EXCEL project and join us in shaping the future of precision medicine for asthma and COPD! For a more detailed description of the PhD projects please visit the website.
Charting Cellular & Molecular Mechanisms of Disease (Mechanisms)
To define asthma and COPD endotypes, we will study cellular and molecular mechanisms in lung tissue. Using existing datasets and advanced techniques, we will map gene regulatory networks and predict responses. We will analyze lung tissue with spatial transcriptomics, proteomics, and lipidomics to identify disease mechanisms and treatment targets. RESPIRE-EXCEL partners will support these integrated analyses.
Identifying Disease Endotypes for Patient Stratification (Biomarkers)
To stratify patients for precision medicine, we need biomarkers in nasal swabs or blood that reflect lung disease mechanisms. We will analyze samples from asthma and COPD patients using advanced techniques to identify patient clusters and link them to disease mechanisms. This will help distinguish asthma and COPD endotypes for targeted treatments.
Cellular & Molecular Basis for Treatment Responses to Biologicals (Treatment)
To achieve disease remission with precision medicine, we will identify which asthma and COPD endotypes respond to treatments like Tezepelumab, Dupilumab, and Mepolizumab. We will analyze patient samples before and after treatment using scRNA-seq, immunohistochemical analyses, and functional studies. This will help identify responder and non-responder endotypes, explore new treatments, and understand treatment responses.
Endotype-based Models for Validation of Targets and Biomarkers (Models)
Current treatments may not cover all asthma and COPD endotypes. We will identify and validate targets for additional endotypes. RESPIRE-EXCEL will create a comprehensive lung disease atlas, integrating various datasets. We will also develop COPD model atlases using scRNA-seq data from patients, cultured cells, and mouse models. This will guide target validation and drug discovery. Additionally, we will generate primary cell culture models to study endotype-specific mechanisms using air-liquid interface and 3D epithelial organoid culture models.
Please apply via the bleow link: https://werkenbijumcg.nl/-/vacatures/phd-positions-to-study-precision-medicine-for-respiratory-diseases/10419-02s0009emp
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.
The University has a responsibility to ensure that all employees are eligible to live and work in the UK.
