Closing date: 25/03/2024
MB-PhD Project: Smaller, Better, Faster, Stronger: real-time colorectal cancer management using nanopore sequencing
Lead Supervisors: Dr Florent Mouliere
Co-Supervisors: Dr Kalena Marti, Dr Michael Braun, Dr John Knight, Dr Dominic Rothwell
Applications Deadline: Monday 25 March 2024
Project Keywords: Nanopore sequencing; Colorectal cancer; Liquid biopsy
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB
The project supervisor is offering a PhD in the below area during 2024/2025. Work during the Summer Placement might involve some of this work but could vary.
Colorectal cancer (CRC) is ranking among the leading causes of cancer-related morbidity and mortality and where early onset is increasing. Timely and accurate diagnosis is crucial and traditional diagnostic methods, though informative, are slow, often taking weeks, hindering swift clinical decisions in CRC. Liquid biopsy and cell-free DNA (cfDNA) are alternatives for biomarkers, but current methods share limitations in analysis turnaround time. Sensitive analysis in blood is challenging due to the dilution of tumour signal.
Nanopore sequencing is a promising technology for cancer diagnostics. Utilizing protein nanopores, it directly sequences DNA offering real-time sequencing, long-read capability, combined with high portability. In CRC, nanopore sequencing shows promise for swiftly detecting mutations and structural variations compared to conventional methods. In other malignancies, nanopore coupled with AI analysis determines cancer subtypes within hours, even during surgery. However, sensitivity may be limited compared to the commonly used short-read technologies in liquid biopsy applications.
Our aim is to develop a nanopore sequencing method for identifying genetic and epigenetic patterns in CRC tissue and liquid biopsy within <24 hours of sampling.
The research plan consists in:
- Improving the sample preparation to accelerate the isolation of cfDNA from hours to minutes using banked control plasma.
- Developing a CRC gene panel for the deep sequencing of mutation from targeted loci.
- Developing a protocol for the genome-wide analysis of mutations and methylation from plasma and tissue samples based on standard native DNA nanopore sequencing.
- In collaboration with bioinformatician, implementing the code to perform the sequencing analysis in a reproducible and fast manner.
- In collaboration with AI specialist, supervising with deep learning the analysis of data to accelerate the turn-around time of reporting interpretable results.
- Applying the approach to a range of clinical samples from CRC patients to matched banked tissue and blood samples from patients before therapy (MCRC biobank) alongside a new prospective sample collection.
About Prof. Florent Mouliere (project Lead Supervisor)
Florent is a team leader at the Cancer Research UK Cancer Biomarker Centre, University of Manchester and assistant professor at the UMC Amsterdam.
His interests are developing new technologies and multi-omics analysis to study extracellular biology, and nucleic acids in cancer and other pathologies.
About the lab group
Find out more about the lab group involved in this project and how we support your wellbeing, learning and career development.
As a PhD lead supervisor, my primary goal is to foster a dynamic and intellectually stimulating research environment that cultivates curiosity, innovation, and academic excellence toward translational research. In my lab, we prioritize a multidisplinary and collaborative culture where diverse perspectives are valued and encouraged. I aim to create an atmosphere where communication is open and direct, and team members feel comfortable sharing ideas and challenging each other’s thinking.
I have high expectations for research quality and rigor, and I believe in setting ambitious yet achievable goals. Regular meetings will be planned to track progress, addressing challenges, and refining research directions. I encourage a proactive approach to problem-solving and expect students to take ownership of their projects. Additionally, I value the importance of convergence science and aim to facilitate opportunities for students to engage with scholars from various fields.
All students provide presentations within lab meetings on a regular basis to engage with their laboratory group. For formal supervisor meetings, students should be able to discuss and show understanding of their project to a high level, with the meetings designed primarily to support and give constructive advice to the student.
Guiding toward independence is a key aspect of my mentoring philosophy. I will provide personalized guidance via one-to-one meetings, constructive feedback on reports, and creating opportunities for students to showcase their work during weekly lab meetings, and monthly centre meetings. I am committed to supporting their career development by providing mentorship on research skills, networking, and navigating academic, service or industry landscapes. I believe in nurturing not only their academic abilities but also their professional skills, ensuring they are well-prepared for diverse career paths.
The Cancer Biomarker Centre (CBC) is a welcoming environment, where basic, translational, and clinical scientists work in tandem with mutual respect. CBC students are embedded in a supportive network of integrated teams with day-to-day supervision by team leads and deputies. We have 3 clinical fellows and 9 students currently.
Recognising the importance of work-life balance, I am dedicated to creating an environment that supports the well-being of my students. I advocate for a healthy integration of work and personal life, promoting strategies for time management and stress reduction. I prioritize a supportive culture that understands the challenges individuals may face and encourages open communication to address and accommodate those needs. Overall, my goal is to guide students towards successful and fulfilling academic and professional journeys while fostering a positive and balanced lifestyle.
Find answers to some common questions about our MB-PhD summer placement.
To apply for our MB-PhD summer placement, you must be:
A University of Manchester MBChB student:
- currently studying in Year 1 or 2
A University of St Andrews Medicine BSc (Hons) student on the Manchester course pathway:
- currently studying in Year 1 or 2
International applicants (including EU nationals) must ensure they meet the relevant academic eligibility criteria (including English Language).
Placement weeks will be arranged between students and supervisors over the summer before the start of the next academic year (2-6 September).
University of St Andrews students can apply for funding from their university to cover expenses.
These placements are unpaid but students at The University of Manchester interested in undertaking a summer placement and unable to do so due to financial reasons should get in touch with Georgina Binnie-Wright, Postgraduate Programme Manager, at MCRCTraining@manchester.ac.uk, to discuss.
Students who are interested in this opportunity should send the following details to Georgina Binnie-Wright, Postgraduate Programme Manager, at MCRCTraining@manchester.ac.uk:
- Your name
- Current year of MBChB study
- Are you intending to apply to the MB-PhD programme in future? (Yes/No)
- Are you applying for this opportunity due to a general interest in academic research? (Yes/No)
- 200 words maximum on why you are interested in a placement
- Lab preference(s)
Depending on how much interest is shown, preference may be given to students who are eligible to apply to the MB-PhD programme in the 2024-25 recruitment round.
Expressions of interest should be returned by Monday 25 March 2024.
- Application deadline: 25 March 2024
Find out more about our MB-PhD Studentships which allow you to study a fully-funded PhD alongside your medical degree.
Read first-hand experiences of from cancer scientists from across Manchester.