Improved Characterization of Chronic Wounds in RDEB

This project aims to develop and test an innovative way to assess wounds and wound healing in the inherited blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB). Working on frozen skin sections and later human wounds, the goal is to use nanoneedle patches to harvest biomolecules (RNA, proteins and lipids) to generate a replica of the molecular profile of the tissue with single cell resolution. The analyses will encompass Raman spectroscopy and complementary Mass Spectrometry Imaging with machine learning classification algorithms for label-free biomolecular profiling of nanobiopsies. Correlating molecular profiles with clinical status/skin histology is expected to help develop a novel mode of assessment for wound healing and comparative testing of novel wound dressings.

After the initial work on skin sections, the project will then expand to in vivo sampling from patients to develop a more dynamic readout of the status of an RDEB wound. The goal is then to begin to use the technology to assess the impact of various wound care dressings on wound healing. Clinical aspects of the project will be supported by Professor John McGrath and Professor Jemima Mellerio within the Department. Thus, this project aims to develop and test an innovative way to assess wounds and wound healing in RDEB by molecular fingerprinting.

This studentship centres on developing a new nanoscale biopsy (nanobiopsy) approach using nanoneedles (co-supervisor Dr Ciro Chiappini is a pioneer in this field and will manufacture the nanoneedles). Nanoneedles are essentially a “bed of nails” with nanoscale dimensions (20nm tip and 4000nm length) fabricated in patches that can be as large as 10 cm in diameter. The nanoneedles are fabricated from porous silicon, a widely employed material for drug delivery, which is effective at delivering payloads, highly cytocompatible, and proven to be safe in vivo across multiple administration routes.  We have shown that rapid nanoneedle application (nanoinjection) can deliver plasmids to cells in skin, skeletal muscle and epicardium for topical gene therapy. Moreover, we have established that nanoinjection does not elicit an observable, acute or chronic immune response.

More significantly with regards to this studentship, applying a nanoneedle patch to tissue for a few seconds permits harvesting of enough biomolecules for analysis - including RNA, proteins and lipids - generating a replica of the molecular profile of the tissue (nanobiopsy). With this approach one can map cancer biomarkers with single cell resolution across clinical samples of tumour margins. Raman Spectroscopy Imaging (RSI) is a label-free and minimally invasive optical technique that provides a point-wise optical fingerprint of the myriad of inter- and intra-cellular building blocks (i.e., proteins, lipids and DNA) of tissue at the biomolecular level. Complementarily to RIS’s potential for high spatial resolution imaging of molecular fingerprints, Mass Spectrometry Imaging (MSI) provides highly specific biomolecular identification with lower spatial resolution.  Recently, we have developed a workflow that combines confocal Raman spectroscopy (RSI) and complementary Mass Spectrometry Imaging (MSI) with machine learning classification algorithms (work developed by co-supervisor Dr Mads Bergholt) for label-free biomolecular profiling of nanobiopsies.

The student will be an integral part of the St John’s Institute of Dermatology Genetics Skin Disease research group (School of Basic and Medical Biosciences), headed by Professor John McGrath but the project will also involve working with the KCL research groups headed by Dr Ciro Chiappini (Senior Lecturer in Nanomaterials and Biointerfaces, Faculty of Dentistry, Oral & Craniofacial Sciences) and Dr Mads Bergholt (Lecturer in Biophotonics, Faculty of Dentistry, Oral & Craniofacial Sciences).

Training:

All students are regularly notified about skills development opportunities through a monthly Postgraduate Research Newsletter. Participation in the annual Postgraduate Research Symposium is compulsory for all students and provides an opportunity to improve science communication and presentation skills. All postgraduate students in the School of Basic and Medical Biosciences present their research as part of departmental seminar programmes as well as to their research groups. Opportunities are available for postgraduate students to present their work at national and international scientific meetings. Our postgraduate students can also apply to assist with teaching of undergraduates as demonstrators in practical classes or leading tutorials.

Please visit Improved Characterization of Chronic Wounds in RDEB (kcl.ac.uk for details on how to apply.