Smaller, Better, Faster, Stronger: real-time colorectal cancer management using nanopore sequencing

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.

Project Outline

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: 

  1. Improving the sample preparation to accelerate the isolation of cfDNA from hours to minutes using banked control plasma.
  2. Developing a CRC gene panel for the deep sequencing of mutation from targeted loci. 
  3. Developing a protocol for the genome-wide analysis of mutations and methylation from plasma and tissue samples based on standard native DNA nanopore sequencing. 
  4. In collaboration with bioinformatician, implementing the code to perform the sequencing analysis in a reproducible and fast manner. 
  5. In collaboration with AI specialist, supervising with deep learning the analysis of data to accelerate the turn-around time of reporting interpretable results. 
  6. 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.

Cancer Research UK Manchester Centre | Smaller, Better, Faster, Stronger: real-time colorectal cancer management using nanopore sequencing

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Florent Mouliere's lab group

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