09:05-09:15
Mechanobiology-based technology for rapid cancer diagnosis and prognosis
Professor Daphne Weihs, Technion-Israel Institute of Technology, Israel
Abstract
Metastasis requires cells to dynamically adapt to changing microenvironments and apply forces. Daphne Weihs shows that subpopulations of metastatic cells rapidly (<2 hours) and forcefully indent elastic, physiological stiffness, synthetic, impenetrable gels to depths of 1–20 µm, whereas benign/normal cells do not indent. The indenting subpopulation is highly migratory and invasive (Boyden chamber) and includes chemotherapy-resistant and cancer stem cells. Indentation capacity is governed by mechanobiology and is applicable to various solid cancers. Daphne will demonstrate with breast, pancreas, and skin cancers, rapid, same-day diagnosis and prognosis that matches the metastatic risk and clinical outcome in patients.
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Professor Daphne Weihs, Technion-Israel Institute of Technology, Israel
Professor Daphne Weihs, Technion-Israel Institute of Technology, Israel
Associate Professor Daphne Weihs is a Professor of Biomedical Engineering at the Technion-Israel Institute of Technology since 2006. She obtained her BSc, MSc, and PhD (2004) at the Faculty of Chemical Engineering, Technion. She did her post-graduate research at the Department of Pathology and Lab Medicine, Medical School, University of California at Los Angeles (UCLA, 2004–2006). Professor Weihs is the head of the Scientific Committee of the Israel Society of Medical and Biological Engineering (ISMBE) since 2015. Her focus is the mechanobiology of cells; the stiffness and dynamics of cells and their mechanical interactions with the microenvironment, in the contexts of cancer progression and in wound prevention and healing. She has recently developed a mechanobiology-based approach to diagnose cancer and predict metastases.
09:15-09:30
Using mesoscopic models to understand the physical behaviours of cells and tissues
Dr Mike Murrell, Yale University, USA
Abstract
Living cells generate and transmit mechanical forces over diverse time-scales and length-scales to determine the dynamics of cell and tissue shape during both homeostatic and pathological processes. On the molecular scale, Mike Murrell’s group uses active gels as a framework to understand how mechanical stresses are transmitted within the cell cytoskeleton. On the scale of cells and tissues, they abstract these stresses to surface tensions in a liquid film and draw analogies between the dynamics of wetting to the shape dynamics of simple tissues. Together, they develop comprehensive descriptions for how cytoskeletal stresses translate to the physical behaviours of cells and tissues.
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Dr Mike Murrell, Yale University, USA
Dr Mike Murrell, Yale University, USA
Murrell’s interests are in understanding the mechanical principles that drive major cellular life processes through the design and engineering of novel biomimetic systems. To this end, he develops simplified and tractable experimental models of the mechanical machinery within the cell with the goal of reproducing complex cellular behaviour, such as cell division and cell migration. Murrell then combines these ‘bottom-up’ experimental models with concepts from soft matter physics to gain a fundamental understanding of the influence of mechanics on cell and tissue behaviour. In parallel, he hopes to identify new design principles from biology which can be used to create novel technologies.
09:30-09:45
Development of biomimetic stroma for 3D tumouroids
Dr Umber Cheema, University College London, UK
Abstract
There has been a drive to develop 3D models to test mechanisms of cancer progression. Such models aim to recapitulate specific aspects of the native microenvironment of cancer tissue. Umber Cheema’s group has developed 3D models of solid cancers, termed tumouroids. Using tissue engineering techniques, they control the spatial positioning of a cancer mass and its surrounding stroma. The group are able to engineer specific components into each component. They have engineered hypoxic gradients within the 3D model as well as engineering an intact primitive vascular network in the stromal component. They have observed interaction of cancer cells with engineered vascular networks- and measured angiogenic remodelling of the networks. By incorporating cancer associated fibroblasts from patient samples Umber is further investigating how these cells enhance cancer invasion and the mechanisms by which this is done.
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Dr Umber Cheema, University College London, UK
Dr Umber Cheema, University College London, UK
Dr Cheema is a senior lecturer in tissue engineering, and head of education for the Division of Surgery at UCL. Her research interests include engineering vascular networks in 3D engineered tissues to further understand the role native matrix density and composition have on this biological process. Her research also focuses on controlling elements of collagen architecture to build biomimetic tissues in vitro. In particular, by studying mechanisms which control collagen fibril alignment, diameter and density. Her work on engineering tissues has resulted in the development of 3D in vitro models of solid tumours or tumouroids. Here the spatial architecture of a tumour and its surrounding stroma has been reproduced in vitro, with evidence of tumour invasion into surrounding 'normal' tissue. Engineered tumouroids include epithelial cancers and sarcoma's. Her collaborative work includes engineering basic tissue models which are subjected to decompression regimes to mimic the 'bends' in diving. Experimental data has been modeled to further our understanding of how bubbles nucleate, grow and coalesce in tissues during decompression.
09:45-10:00
Mechanobiology in a microplate – opportunities for high throughput screening
Dr Chris Toseland, University of Kent, UK
Abstract
Mechanobiology focuses on understanding how physical forces correlate with protein, cell and tissue dynamics and organization through mechano-transduction. Single molecule force measurements have revealed how force is used in biological systems, from individual proteins to complexes. These changes occur through alteration of biochemical properties, yet such properties cannot be readily measured alongside force manipulation experiments. To this end Chris Toseland has developed a novel mechanobiology assay format to encompass mechanical measurements with biochemical and cellular assays using a modified microplate system. He demonstrates his group’s approach using force-induced in vitro enzymatic activity and conformation changes, along with receptor activation of signalling pathways in live cells.
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Dr Chris Toseland, University of Kent, UK
Dr Chris Toseland, University of Kent, UK
Chris Toseland (CT) is an MRC Career Development Award holder at the University of Kent. The research group was established in 2015 with a focus upon the regulation of motor proteins in transcription. CT gained his PhD from the MRC National Institute for Medical Research in biochemistry/biophysics before applying single molecule methods during post-doctoral positions at the LMU Munich and Max Planck Institute for Biochemistry. The Toseland group now applies a range of biophysical and single molecule imaging methods. The group also develops novel methodologies and was recently awarded a Cancer Research UK Pioneer Award for the development of new mechanobiology tools.
10:00-10:30
Discussion
Professor Daphne Weihs, Technion-Israel Institute of Technology, Israel
Dr Mike Murrell, Yale University, USA
Dr Umber Cheema, University College London, UK
Dr Chris Toseland, University of Kent, UK
Show speakers
Professor Daphne Weihs, Technion-Israel Institute of Technology, Israel
Dr Mike Murrell, Yale University, USA
Dr Umber Cheema, University College London, UK
Dr Chris Toseland, University of Kent, UK
Professor Daphne Weihs, Technion-Israel Institute of Technology, Israel
Associate Professor Daphne Weihs is a Professor of Biomedical Engineering at the Technion-Israel Institute of Technology since 2006. She obtained her BSc, MSc, and PhD (2004) at the Faculty of Chemical Engineering, Technion. She did her post-graduate research at the Department of Pathology and Lab Medicine, Medical School, University of California at Los Angeles (UCLA, 2004–2006). Professor Weihs is the head of the Scientific Committee of the Israel Society of Medical and Biological Engineering (ISMBE) since 2015. Her focus is the mechanobiology of cells; the stiffness and dynamics of cells and their mechanical interactions with the microenvironment, in the contexts of cancer progression and in wound prevention and healing. She has recently developed a mechanobiology-based approach to diagnose cancer and predict metastases.
Dr Mike Murrell, Yale University, USA
Murrell’s interests are in understanding the mechanical principles that drive major cellular life processes through the design and engineering of novel biomimetic systems. To this end, he develops simplified and tractable experimental models of the mechanical machinery within the cell with the goal of reproducing complex cellular behaviour, such as cell division and cell migration. Murrell then combines these ‘bottom-up’ experimental models with concepts from soft matter physics to gain a fundamental understanding of the influence of mechanics on cell and tissue behaviour. In parallel, he hopes to identify new design principles from biology which can be used to create novel technologies.
Dr Umber Cheema, University College London, UK
Dr Cheema is a senior lecturer in tissue engineering, and head of education for the Division of Surgery at UCL. Her research interests include engineering vascular networks in 3D engineered tissues to further understand the role native matrix density and composition have on this biological process. Her research also focuses on controlling elements of collagen architecture to build biomimetic tissues in vitro. In particular, by studying mechanisms which control collagen fibril alignment, diameter and density. Her work on engineering tissues has resulted in the development of 3D in vitro models of solid tumours or tumouroids. Here the spatial architecture of a tumour and its surrounding stroma has been reproduced in vitro, with evidence of tumour invasion into surrounding 'normal' tissue. Engineered tumouroids include epithelial cancers and sarcoma's. Her collaborative work includes engineering basic tissue models which are subjected to decompression regimes to mimic the 'bends' in diving. Experimental data has been modeled to further our understanding of how bubbles nucleate, grow and coalesce in tissues during decompression.
Dr Chris Toseland, University of Kent, UK
Chris Toseland (CT) is an MRC Career Development Award holder at the University of Kent. The research group was established in 2015 with a focus upon the regulation of motor proteins in transcription. CT gained his PhD from the MRC National Institute for Medical Research in biochemistry/biophysics before applying single molecule methods during post-doctoral positions at the LMU Munich and Max Planck Institute for Biochemistry. The Toseland group now applies a range of biophysical and single molecule imaging methods. The group also develops novel methodologies and was recently awarded a Cancer Research UK Pioneer Award for the development of new mechanobiology tools.