Prof Martin Knight
BEng, MSc, PhD, FHEA
On this page:
- Current Funded Research Projects
- Previous Funded Research Projects
- Previous PhD Studentship Projects
- Other Research Projects
Current Funded Research Projects
Development of an Organ-on-a-chip model of polycystic kidney disease using CRISPR modified human kidFunding source: Kidney Research UK
Start: 01-12-2023 / End: 30-11-2025
Start: 01-04-2022 / End: 31-03-2025
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.
Start: 01-01-2021 / End: 31-05-2024
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 …
Start: 01-02-2023 / End: 31-01-2024
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
Start: 20-08-2019 / End: 31-12-2023
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/
Previous Funded Research Projects
Start: 01-10-2018 / End: 01-09-2023
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.
Start: 24-08-2020 / End: 23-08-2023
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
Start: 01-10-2017 / End: 24-07-2023
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
Start: 24-07-2022 / End: 28-02-2023
Start: 01-01-2021 / End: 31-12-2022
Start: 01-08-2018 / End: 30-09-2022
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.
Start: 29-09-2020 / End: 01-03-2022
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.
Start: 13-02-2020 / End: 12-08-2021
Start: 01-10-2018 / End: 30-09-2020
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.
Start: 01-01-2018 / End: 31-07-2020
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.
Start: 01-10-2019 / End: 31-03-2020
Start: 01-09-2014 / End: 30-03-2020
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 stimulationFunding source: EPSRC OA Tech Network plus Pump-Priming Project Grant
Start: 01-07-2019 / End: 31-12-2019
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.
Start: 07-05-2019 / End: 07-11-2019
Start: 01-09-2016 / End: 31-10-2019
A high throughput screen of 1721 FDA approved small molecules will be conducted to identify compounds that regulate cilia expression in primary bovine chondrocytes.
Start: 03-10-2016 / End: 02-01-2019
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 ...
Start: 01-05-2018 / End: 01-12-2018
Start: 26-08-2013 / End: 24-08-2018
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.
Start: 14-03-2012 / End: 10-05-2017
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.
Start: 05-05-2015 / End: 04-09-2016
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.
Start: 31-12-2015 / End: 31-07-2016
Start: 01-02-2013 / End: 31-05-2016
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 . 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
Start: 01-10-2012 / End: 30-09-2014
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 …
Start: 01-09-2007 / End: 31-08-2012
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 ...
Start: 02-02-2009 / End: 01-02-2012
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 …
Start: 09-11-2000 / End: 10-11-2006
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 …
Start: 01-01-2199 / End: 10-09-2006
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 …
Start: 01-01-2199 / End: 22-03-2006
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 …
Previous PhD Studentship Projects
Start: 03-09-2018 / End: 02-09-2022
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.
Start: 04-04-2018 / End: 03-04-2021
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.
Start: 29-09-2015 / End: 28-09-2019
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
Start: 01-09-2015 / End: 01-09-2019
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
Start: 07-10-2013 / End: 06-10-2017
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 ...
Start: 10-10-2013 / End: 20-06-2017
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 ...
Start: 09-10-2012 / End: 10-10-2016
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 ...
Start: 30-09-2011 / End: 01-10-2015
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
Start: 09-01-2012 / End: 10-01-2015
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 …
Start: 01-10-2009 / End: 30-09-2013
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 …
Start: 01-10-2009 / End: 02-10-2012
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 …
Start: 01-09-2007 / End: 31-08-2010
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 constructsFunding source: EPSRC
Start: 01-09-2006 / End: 31-08-2010
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 …
Start: 02-10-2006 / End: 30-09-2009
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.
Other Research Projects
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_…
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 …