Automated sampling of cell-free DNA from blood using engineered hydrogel-filled nanopores: Improving diagnostic/prognostic tests for prostate cancer

ThomasCurrent tests for the diagnosis, prognosis and stratification of prostate cancer suffer from two main drawbacks, being either invasive (requiring biopsies) or inaccurate and therefore unreliable. To reduce the current overtreatment with associated morbidity, it is imperative to distinguish men who will benefit from aggressive treatment from those who won’t and those who don’t require it. Recent studies have highlighted the potential of plasma cell-free nucleic acids (cfNA) as non-invasive diagnostic and prognostic biomarkers for various clinical pathologies, including cancer. There is currently no gold standard technology to achieve size profiling of endogenous cfNA of unknown sequences with high enough resolution and sensitivity. Furthermore, all available technologies require heavy sample processing (no clear answer from whole blood) which, in the absence of standardised procedures is a significant source of error.

This project will use quartz nanopores filled with engineered hydrogels for: (1) automated sampling / size sorting and genomic analysis of cfNA from human plasma to investigate a specific size enrichment of tumoural cfNA compared to non-malignant sources and (2) cfNA size profiling, and characterisation of new molecular signatures for improved diagnosis and prognosis of prostate cancer

The project is co-supervised by. Jointly funded by the CRUK Imperial Centre CDT and Institute of Chemical Biology.

Mini-bio

  • PhD, Chem department, Imperial (since 2018) Supervisors:  prof Charlotte Bevan, prof Joshua Edel and Dr Sylvain Ladame
  • Research Associate, Advanced Diagnostic Pathology Unit, Health Services Laboratories (2018-2018). The ADPU continues work from the ICONIC project optimising and integrating Next Generation Sequencing into the NHS as diagnostic option for viruses.
  • Research Assistant, Department of Infection and Immuntity, UCL (2017-2018) ICONIC project to delivering the clinical evaluation of the Next Generation Sequencing diagnostic platforms for viral genomes. PI: Dr Zisis Kozlakidis
  • Research Technician, Department of Developmental Biology & Cancer, UCL (2016-2017) Developing a chimeric antigen receptor immunotherapy targeting ALK inhigh grade neuroblastoma. PI: Prof John Anderson
  • Msc, Department of Cancer Biology, UCL (2014-2015) Project: ‘Development of an epigenetic assay to detect treatment specific changes in cancer’. Supervisors:  prof Stephan Beck, Dr Nischalan Pillay
  • Bsc, Department of Natural Sciences, Uni of Bath (2011-2014)
  • Project: ‘Novel targets in the Extracellular Matrix: Targeting acquired resistance to metastatic factors in non-small cell lung cancer’

Publications

  • Pataillot-Meakin T, Pillay N, Beck S, 2016, 3-methylcytosine in cancer: an underappreciated methyl lesion?, Epigenomics, 8(4):451-4