Out-of-body experiences: Ex Vivo Culture Techniques and Research Opportunities

TOPICAL COLLECTIONS

Guest Editors

Arran Turnbull

University of Edinburgh

Dr. Arran Turnbull is a senior lecturer and group leader of the Translational Oncology Research Group at the Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh. Arran's research focuses primarily on understanding, predicting and treating resistance to endocrine therapy and other therapeutics in breast cancer patients. Arran's undergraduate honours degree was in molecular biology at Heriot-Watt University. This was followed by a masters by research in immunology, genetics and pathway medicine at the University of Edinburgh. Arran graduated from his PhD in oncology at the University of Edinburgh in 2012 and took up a post-doctoral research position in the Edinburgh Breast Cancer Now Research Team before going on to form his own research group in 2017. Arran's PhD focused on the successful development and validation of a translational predictive test for endocrine therapy response in breast cancer for which he, the research team and the University of Edinburgh now hold the UK patent. This test has been successfully validated in several independent cohorts of patients and is moving towards a prospective clinical trial both in the UK and USA. Arran is also the principal investigator of research projects focused on DCIS, radiotherapy response and microwave radiometry for breast cancer diagnosis and prostate cancer.

Carlos Martinez-Perez

University of Edinburgh

Following an undergraduate degree in Biotechnology from the Polytechnic University of Valencia, Dr. Carlos Martínez-Pérez gained an MSc in Molecular Medicine in Cranfield University, followed by a PhD in Molecular and Clinical Medicine (Pathology) in the University of Edinburgh, working on a SULSA BioSkape industrial collaboration project focused on pre-clinical drug development in breast and ovarian cancers. Following completion of his PhD, Dr. Martínez-Pérez joined the Breast Cancer Now Edinburgh and Translational Oncology Research groups at the MRC Institute of Genetics and Molecular Medicine, led by Prof. Mike Dixon OBE and Dr. Arran Turnbull, as a postdoctoral researcher. His translational breast cancer research focuses on biomarker discovery and the development of novel diagnostic tools which could be of use to address current clinical needs. Projects to date have included a Breast Cancer Institute-funded study on ductal carcinoma in situ of the breast (DCIS) and work on a large international study of genomic aberrations linked to the development of resistance to treatment, supported by funding from Breast Cancer Now.

Mark Gray

University of Edinburgh

Dr. Mark Gray gained his Bachelor’s degree in veterinary medicine and surgery in 2004. After obtaining post-graduate surgical qualifications with the Royal College of Veterinary Surgeons, he completed his Masters by Research and then a PhD in Molecular and Clinical Medicine with Prof. David Argyle at the University of Edinburgh. Here, Dr. Gray worked as part of the IMPACT (Implantable Microsystems for Personalised Anti-cancer Therapy) project, which aimed to develop miniaturised sensors that could be implanted into solid tumours to measure intra-tumoural oxygen and pH. Dr. Gray’s role was to develop novel small and large animal models that would validate sensor functionality. A secondary aim of his PhD was to develop novel in vitro radioresistant cell lines, which were used to characterise cancer cell radioresistance and secreted proteins related to radiation response. Dr. Gray now works as a lecturer in large animal research; he splits his time between his own research projects, including the development of large animal surgical translational models of human diseases and teaching at the Royal (Dick) School of Veterinary Studies, The University of Edinburgh.

James Meehan

University of Edinburgh

Dr. James Meehan obtained his Bachelor’s degree in Neuroscience, graduating in 2011 from Trinity College Dublin, Ireland. He moved to the UK after receiving a scholarship to study at The University of Edinburgh. Here he completed a MSc by research in Biomedical Sciences before moving into a PhD in Molecular and Clinical Medicine, investigating the potential of 3 different pH regulating proteins to act as therapeutic targets in breast cancer, using both novel and commercially available inhibitors and employing a combination of in vitro and ex vivo cancer models in 2D/3D cell culture environments. Following the conclusion of his PhD, he worked as a Research Associate at Heriot-Watt University on the IMPACT (Implantable Microsystems for Personalised Anti-Cancer Therapy) project, a £5.2 million programme grant that aimed to develop miniaturised sensors to monitor the status of individual tumours. After the completion of the IMPACT project, Dr. Meehan went onto work within the Translational Oncology Research Group at The University of Edinburgh. Dr. Meehan’s research currently focuses on the identification and validation of novel biomarkers of radiotherapy response.

Collection Overview

In vitro model systems are essential in scientific research, where they can be used to investigate the expression of disease-related genes/proteins or to assess the therapeutic effects of emerging drug candidates. Historically, most studies rely on established cell lines grown in 2D cultures. Unfortunately, these models lack the cellular/tissue heterogeneity observed within the body. This issue is especially highlighted in the cancer drug development field, where attrition rates for new therapeutics are very high, with only 5% of agents that show pre-clinical promise gaining a license to be used in patients. 3D cell culture systems aim to better mimic the structural and functional properties of tissues. However, many of these 3D model systems are still limited by their inability to accurately account for the in vivo microenvironment. The ex vivo culture of tissue and the culture/expansion of rare cells within the body (such as circulating tumour cells) can overcome many of these limitations, including the maintenance of tissue morphology with the presence of stromal and immune cells (tissue samples) and cellular heterogeneity (tissue and liquid biopsy samples). These models bridge the gap between cell-based assays and in vivo studies and can increase our molecular understanding of diseases and improve pre-clinical drug development. This methods collection will highlight aspects of ex vivo cell and tissue culture and the multitude of research opportunities that these techniques provide for both human and veterinary applications.