Development of an Organ-on-a-chip model of polycystic kidney disease using CRISPR modified human kid

Human synovium-cartilage organ-chip for personalised surgical screening

Scientists at Queen Mary University of London are creating a human knee-on-a-chip device to understand how arthritis develops in individual patients and to test treatment strategies. The so-called organ-on-a-chip will consist of living cells taken from the knee joints of patients with osteoarthritis. The cells from patient’s cartilage and other tissues within the knee, will be grown within the laboratory in a carefully bioengineering organ-on-a-chip and used to understand which patients respond well to treatment. This will ultimately allow clinicians to optimise therapies to individual patients in an approach known as precision medicine or personalised medicine.

Organ-on-a-chip model of breast cancer bone metastases

Background A common site for invasive ductal carcinomas (IDC) metastasis is bone, affecting about 70% of patients. Once metastasis to bone has occurred the five-year survival rate drops from 99% to 29%.  How breast cancer metastasises to bone is poorly understood, partly because of the lack of appropriate models. Organ-on-a-chip technology is …

Production of a human growth plate organ-chip model of skeletal development

This award aims to develop a human cell-based skeletal growth plate organ-on-a-chip to replace the use of rodents in some studies of development, ageing and disease

Organ-on-a-chip Centre of Excellence

The QM-Emulate Organs-on-Chips Centre provides access to Emulate’s Organs-on-Chips technology to enable researchers to develop organ models of their design to expedite their experiments. Expert staff are on hand to support with training and use of the platform as well as pushing forward new organ-on-a-chip research projects led by Knight and Screen. The Centre also provides opportunities for collaboration with Emulate and support for commercialisation and translational impact. The centre is part of the new Centre for Predictive in vitro Models (CPM). Visit the web site to see full details of this and the new Emulate centre: https://www.cpm.qmul.ac.uk/emulate/

Targeting the innate immune system in high grade serous ovarian cancer

This 5-year CRUK Programme Grant is led by Prof Fran Balkwill from Barts Cancer Institute with a multidisciplinary team of co-investigators including Prof Martin Knight representing cancer bioengineering and mechanobiology.

MICA: Organ-on-a-chip models for safety testing of regenerative medicine products

We are building novel organ-on-a-chip models of our musculoskeletal tissues, to learn more about disease processes and how this might be managed with regenerative medicine approaches

The mechanics of the collagen fibrillar network in ageing cartilage

We seek to understand how age-related changes in articular cartilage link to alterations in its nanoscale mechanics – and eventually to joint breakdown. We use high-brilliance synchrotron X-ray scattering to track fibrillar deformation dynamics in the matrix (hydrated proteoglycans restrained by collagen fibrils), combined with proteomics to assess compositional changes. https://gtr.ukri.org/projects?ref=BB%2FR003610%2F1

Correlating structural and proteomic techniques on cartilage

Emulate Organs-on-Chips Centre Technician

Organ-on-a-Chip Technologies Network

We are excited to host the UKRI Technology Touching Life funded Organ-on-a-Chip Network out of QMUL. The network aims to bring together the vibrant, multidisciplinary UK research community interested in developing and using organ-on-a-chip models and support the on going exciting research activity in this field.

Drug repurposing for treatment of cilia-related pathologies

This project funded by Queen Mary Innovations, will identify compounds for the treatment of a rare genetic disease, Jeune Syndrome, that disrupts skeletal formation associated with dysregulation of primary cilia.

EPSRC Core Equipment Call

THESIS

In this project, the Marie Curie Fellow will develop an optical fibre based image-guided surgery system based on the state-of-the-art optical-fibre laser technologies.

META-DORM

This study seeks to explore the interactions between bone cells, cancer cells and their physical environment and the role of primary cilia, aiming to expand our knowledge of how cancer spreads to bone from other organs.

Does the biological clock within cartilage align to diurnal patterns in activity?

Osteoarthritis may be treated as an environmental ciliopathy

This study tests the hypothesis that pathological alterations in the cartilage microenvironment regulate chondrocyte primary cilia structure leading to changes in cilia signalling which drive cartilage degradation.    Increasing evidence suggests that primary cilia and the associated signalling pathways are critical for the health of articular cartilage ...

Development of a synovium-chondrocyte organ-on-a-chip model with integrated biomechanical stimulation

We plan to develop an organ-on-a chip microfluidic model to investigate the effects of mechanical stimulation on the interaction between musculoskeletal cells within the joint. This chip will incorporate the multiple cell types seen in cartilage and the surrounding synovial environment to mimic human tissue architecture, cellular microenvironment and signalling.

Parmaceutical modulation of cilia expression-Miss Jeha Kwon

Innovation Fund: High-throughput Library Screen

A high throughput screen of 1721 FDA approved small molecules will be conducted to identify compounds that regulate cilia expression in primary bovine chondrocytes.

Determining the role of exosomes in cellular senescence and ageing

The number elderly population in the UK has dramatically increased in the last few decades. As a consequence, conditions associated with ageing, such as cancer, cardiovascular and neurodegenerative diseases, are having a huge impact on the public health system and the UK economy. It is therefore imperative to promote research ...

The effect of cobalt ions on primary cilia in bone cells

CANBUILD - Bioengineering the tumour microenvironment

This project is funded by a European Research Council (ERC) Senior Fellowship (PI. Prof Fran Balkwill, Barts Cancer Institute, QMUL) and aims to revolutionise the field of cancer cell research by using bioengineering techniques to grow the first complex 3-dimensional human "tumour microenvironment" in the laboratory.

Wellcome Trust Witnesses to Twentieth Century Medicine

Martin Knight is a technical bioengineering advisor for a large Wellcome Trust public engagement grant held by Tilly Tansey in the History of Modern Biomedicine research group at QMUL. The grant enables the running of Witness Seminars at which significant figures in twentieth-century medicine are invited to discuss specific discoveries or events in recent medical history.

Targeting Tissue Stiffness to Treat Colorectal Cancer

As colon cancer develops and progresses, there are significant changes in the organisation of the web of proteins forming the structure of colon tissue. These changes cause tissue stiffening, which promotes the growth of the cancer.

The role of primary cilia in cartilage health and disease (C Chandrakumar)

Aberrant chondrocyte primary cilia signalling drives cartilage degradation in response to IL-1

Primary cilia are poorly understood cytoskeletal organelles that projects into the extracellular milieu. The chondrocytes cilium acts as a centre for Hedgehog (Hh) signalling which has recently been shown to be up-regulated in osteoarthritis where it drives cartilage degradation [31]. However the mechanisms leading to aberrant Hh signalling have not been ...

Changes in primary cilia length and function modulate the pathogenesis of osteoarthritis in response to lithium

Osteoarthritis has recently been shown to involve aberrant up-regulation of hedgehog signalling leading to increased expression of ADAMTS5 resulting in degradation of the articular cartilage. Hedgehog signalling requires the presence of a primary cilium, a specialised cytoskeletal organelle that projects out from the cell into the extracellular microenvironment. The length …

Multiscale Mechanobiology for Tissue Engineering

Platform Grant Strategic Research Areas i). Mechanics and mechano-signalling at the sub-cellular, cellular and tissue levels. The response of living cells and tissues to mechanical forces is critical to tissue health and homeostasis. Consequently this field of mechanobiology has enormous potential to be exploited in the development of Tissue Engineering ...

The Chondrocyte Primary Cilium - A Purinergic Mechanoreceptor?

The aim of this Wellcome Trust funded research project is to test the hypothesis that the primary cilium acts as a fundamental mechanoreceptor in articular chondrocytes triggering mechanosensitive intracellular calcium signalling via a purinergic pathway that involves the release of ATP. We will elucidate the underlying physiological mechanisms involved in …

Mechanical loading bioreactors for production of tissue engineered cartilage

Background and Context Articular cartilage provides a low friction, low wear bearing surface within synovial joints. The tissue has poor intrinsic repair properties due to its avascular nature and consequently cartilage damage progresses to debilitating arthritis with joint pain and stiffness. Existing repair techniques based on the Pridie method produce …

Mechanical loading modulates cytoskeletal organisation in living chondrocytes

Background and Context Articular cartilage provides a low friction, low wear bearing surface within synovial joints. Existing approaches for treatment of cartilage injury or disease have poor long term functionality, particularly in younger patients. There is therefore a real clinical need for improved cartilage repair techniques. It is well established …

Tissue Engineering Animation Workshops

This EPSRC funded Partnership for Public Awareness was in collaboratiom with City Learning Centre and Centre of the Cell. We ran a series of animation workshops in which groups of school children learnt about different aspects of medical science. This involved a talk from a senior scientist followed by two …

Effect of substrate stiffness on primary cilia signalling

This China Scholarship Council (CSC) studentship examines the effect of substrate stiffness on primary cilia signalling. Initial studies will examine the effect on chondrocyte cilia expression and IFT-dependent inflammatory signalling.

Development of high throughput imaging screen of compounds effecting primary cilia expression and resulting consequences for cilia function.

A high throughput screen of 1721 FDA approved small molecules will be conducted to identify compounds that regulate cilia expression in primary bovine chondrocytes. We will then test the hypothesis that pharmaceutical manipulation of chondrocyte primary cilia expression regulates mechanosignalling.

Changes in primary cilia mediate the anti-inflammatory effects of mechanical loading

This new PhD studentship follows on from our previous work highlighting the importance of primary cilia in inflammation. Here we will examine whether mechanical loading is anti-inflammatory due to its effect on reducing primary cilia length. The study will initially focus on articular cartilage for which IL-1B stimulates cartilage degeneration as seen in osteoarthritis. Previous studies have shown that compressive mechanical loading is anti-inflammatory. Studies have shown that primary cilia are required for inflammatory signalling and are also modulated by mechanical loading. This study aims to identify the effect of mechanical loading on IL-1B induced inflammatory signalling and test the hypothesis that mechanical loading modulates IL-1? signalling by regulating primary cilia length and trafficking. PhD Student: Su Fu

Biophysical characterization of bleb-based migration in cancer cells

We aim to characterize how the cytoskeleton and ERM proteins polarize their intracellular localization as main driver for directed bleb-based cell migration in cancer cells

Collagen nanomechanics in articular cartilage

Determining the depth-dependent relationship between the mechanical behaviour and the composition and structure of articular cartilage is crucial in understanding the changes that develop during osteoarthritic degradation. Currently, little is known as to how the networks of collagen fibrils contribute to the tissue’s mechanics, with the fibrils acting ...

The role of primary cilia in tendinopathy

Tendon is mechanosensitive, maintaining tissue health in response to applied loads. Overload is a key contributor to the development of tendon pathologies, know as tendinopathies; a range of highly debilitating and increasingly prevalent conditions2-3. However, the mechanisms associated with tendinopathy development remain unclear. Current evidence supports a combined mechanical ...

Bioengineering manipulation of primary cilia controls stem cell differentiation

Aim:  To determine the influence of substrate nano-topography and mechanics on primary cilia structure and function and the role of the cilium in directing stem cell differentiation. Background & Hypothesis:  Nano topography and changes in substrate mechanics have been shown to regulate cell behaviour including regulation of stem ...

The influence of osmotic challenge on chondrocyte mechanics

This PhD studentship examines the mechanical properties of articular chondrocytes and the influence of osmotic pressure. In particular hypo osmotic challenge results in an increase in cell size and associated changes in cell mechanics. The study involves quantification of cellular mechanics using micropipette aspiration and analytical modelling and investigation of …

The role of membrane-actin adhesion in regulating stem cell viscoelastic properties and blebability during differentiation

This PhD examines how chondrogenic differentiation of human mesenchymal stem cells (hMSCs) regulates the interaction between the cell membrane and the actin cortex, thereby controlling cell biomechanics. The thesis also investigates the viscoelastic properties of primary articular chondrocytes and the effect of de-differentiation. Micropipette aspiration was used to measure the …

The role of mechanical loading in modulating chondrocyte hedgehog signalling via primary cilia.

Background Chondrocytes express primary cilia consisting of a membrane coated axoneme which projects into the pericellular matrix and an intracellular basal body that comprises the most mature of the two centrioles. The function of this organelle in cartilage is unknown, however recent studies indicate that the primary cilium is involved …

Viscoelastic biomechanics behaviour of living cells at a cellular and subcellular level

The biomechanics of living cells and their response to mechanical forces is critical to the function and health of a variety of tissues including articular cartilage. This field of mechanobiology therefore has enormous potential to be exploited in the evaluation of pharmacological agents and the development of tissue engineering strategies …

Tensile stretch and hypoxia influence the function of isolated neurons

Neurons within the peripheral nervous system experience considerable tensile strains associated with various pathological conditions, and this can result in pain and loss of function. Similarly, spinal cord injury is characterized by a primary mechanical event that produces immediate cell damage or death and a slower phase of delayed secondary …

Development of a multi photon FLIM technique for non-invasive oxygen monitoring in cell seeded constructs

Overall hypothesis: Cell-mediated metabolic gradients within three dimensional cellular structures control the development of spatial patterns of cell viability and differentiation Objectives: To develop and optimise micro-environmental monitoring technologies to assess temporal and spatial gradients of oxygen, glucose and lactate To examine the behavioural responses of selected cells to various …

Ultrasound regulates chondrocytes seeded within tissue engineered scaffolds.

Collaborative project with Smith & Nephew who have funded an EPSRC CASE PhD studentship (Natalie Vaughen). The project investigates the potential of ultrasound to improve the functionality of cartilage tissue engineering and the mechanotransduction pathways through which this occurs.

Urine Flow Analysis: Biophysics to diagnostics

We have developed a new computational model of capillary-waves in free-jet flows, and applied this to the problem of urological diagnosis in this first ever study of the biophysics behind the characteristic shape of the urine stream as it exits the urethral meatus (http://www.youtube.com/watch?v=BXezbw_…

Mathematical modelling of cortex-membrane adhesive failure: viscoelastic deformation of cells

In an cell aspiration experiment, a cell is partially sucked in a micropipette by applying a suction pressure. If the applied pressure is larger than a threshold - which depends sensitive on the cell type - the cell membrane detaches from the underlying cortex, leading to the formation of a …