The regulation of mechanosensing in healthy and atherosclerotic VSMC

Vascular smooth muscle cellsplay a central role in the onset and progression of many cardiovascular diseases, from atherosclerosis to vascular injury, where their migration, matrix secretion, or degradation functions are deregulated. Here we are investigating how the phenotypic switch is regulated through physical/mechanical stimuli.

A Biophysical Model of Gum Reintegration on enamel

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.

Molecular Manufacturing of Macroscopic Objects - fellowship Stoyan Smoukov

This interdisciplinary proposal proposes a molecular basis for Manufacturing for the Future,[a1] to grow many types of particles in a nature-inspired way. It offers scalability, near-full utilization of the material, and the ability to carry out transformations at near ambient conditions. Manufacturing in nature spans the scales from intricate ...

Engineered Protein Nanosheets at Liquid-Liquid Interfaces for Stem Cell Expansion, Sorting and Tissue Engineering

ProLiCell will design the biochemical and mechanical properties of extracellular matrix (ECM) protein nanosheets that can sustain the formation of adhesion protein complexes and support cell proliferation and culture on materials with very weak bulk mechanical properties (liquids).

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

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

UKRMP2 Acellular / Smart Materials

Graphene Flagship Core Project 3

This grant will cofund the establishing of a mini-CDT with 5 PhD studentships in Graphene materials at QMUL.

Newton International Fellowship 2019: Dynamics of microcapsules in inertial two-phase flows

The dynamics of microcapsules in fast liquid-gas flows (i.e., inertial regime) is a fundamental problem that lies in the heart of numerous important applications, such as fast particle/cell sorting, encapsulation, and three-dimensional (3D) cell printing. This project will developed numerical simulation tools and fundamental understanding of the capsule and the two-phase fluid dynamics in inertial flow regimes.

Light4Sight - Light-activated carriers for the controlled delivery of therapeutic peptides in posterior segment eye diseases

The growth of the ophthalmic drug market is primarily driven by an increasing aged population suffering from age- and lifestyle-related diseases such as macular degeneration, diabetic retinopathy, glaucoma, among others. These diseases cause moderate or complete vision loss, resulting in significant reduction in quality of life. Consequently, innovative approaches for the effective delivery of biopharmaceuticals for the treatment of chronic intraocular diseases are required. Currently, intravitreal injection of drugs is the most acceptable and effective method to treat vitreoretinal diseases. By placing the drug in the posterior eye, it evades the ocular barriers common in topical and systemic delivery, allowing higher drug doses to reach the target site. However, treatments require frequent injections to maintain adequate intraocular concentration, which are invasive, increase the risk of adverse effects and pose significant treatment burden on patients and healthcare providers. Thus, alternative ways to deliver these drugs that require less frequent administration need to be developed. Light4Sight aims to develop a novel delivery platform consisting of self-assembling nanocarriers incorporating therapeutic peptides and suspended within a light-sensitive supramolecular hydrogel. The hydrogel can be injected in the vitreous and release of nanocarriers be activated through the irradiation of visible light. This approach provides several benefits: 1) minimizes the use of repeated injections reducing treatment burden; 2) reduces burst release of the nanocarriers avoiding potential dose related toxicity; 3) on-demand release to match patient needs; 4) allows high drug loading for longterm therapy; 5) protects peptide drugs from rapid clearance in the vitreous increasing their half-life.

Modulating tendon micromechanics for injury prevention or management

We are working with TRB Chemedica to understand how bio-lubricants may modulate local tendon mechanics and help manage or prevent tendon injury

Multiscale nuclear mechanobiology within the skin: from biophysical cues to epigenetic effects

The overall objective of the proposed project is to understand how forces are transmitted from the external environment to the nucleus and to determine the subsequent effects on nuclear structure, gene expression, and cell function within the epidermis of the skin. We will use advanced biophysical and imaging techniques to apply forces to single cells, and systems biology methodologies to analyse the changes in DNA structure and gene expression. In addition, we will test the role of internal cellular structures, such as the cytoskeleton, to gain mechanistic insight into these processes. Finally, we will investigate the influence of nuclear mechano-sensing in more complex 3D models of human skin. This is a collaboration with Dr John Connelly (PI)

Investigating the cardiomyocyte rigidity sensing mechanism with micro patterned surfaces and nanopil

The composition and the stiffness of the cardiac extracellular matrix change during development or in heart disease. Cardiomyocytes and their progenitors sense these changes, which decides over Cardiomyocyte fate. Our preliminary data suggested a cardiomyocyte specific rigidity sensing mechanism which we will investigate here in detail.

EPSRC Core Equipment Call

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.

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.

Translating Vasculature-on-a-Chips with a Nephrotoxicity Model

Combined LAPS and SICM for multimodal live cell imaging

A novel instrument will be developed that will revolutionise the ability to monitor cellular processes and cell communication in polarised cells by simultaneously imaging cells apically and basally. This will provide information about apical cell morphology and basal ion concentrations and electrical signals such as cell surface charge and impedance.

Inorganic nitrate treatment reduces inflammation in humans: assessment of mechanisms

nitrite is a gas with a short half life which has shown to have a lot of beneficial properties like anti-oxidation . Here we explore the possibilities to be used as an anti=inflammatory agent.

Identifying the causes of age-related tendon injury

The primary goal of this project is to establish how and where in tendon tendinopathy originates, and to define how the age-related changes in tendon accelerate progression to tendinopathy. Our goal is to identify the specific IFM changes that drive increased injury risk with ageing. This is exciting as we can then continue, in future studies, to develop treatments specifically aimed at preventing, reversing, or mitigating the effects of these changes.

Development of mechanically enhanced osteoinductive synthetic bone graft substitutes

The aim of this project is to develop and test a series of bone graft substitutes with novel pore structures using a perfusion based bioreactor system with flow to waste and closed loop capabilities, that is also able to subject real bone graft substitute granules to direct mechanical perturbation. This system has been validated using human mesenchymal stem cells seeded on BGS with varied strut porosity and will be further optimised to enable screening of new structures.

2D composites with controlled nano-mechanisms

A long standing dogma in cell-based technologies is that bulk mechanical properties of solid substrates are essential to enable cell adhesion, proliferation and differentiation. However, the use of solid materials for cell culture constitutes an important hurdle for the scale up and automation of processes. We recently discovered that protein assembly at liquid-liquid interfaces results in mechanically strong protein layers sustaining cell spreading and directing fate decision. For long term culture, such interfaces lacked toughness and ruptured. This project will develop tough 2D nanocomposites assembled at oil-water interfaces and sustaining long term stem cell culture for applications in regenerative medicine.

Healing the fetal membranes after iatrogenic PPROM

The integrity of the fetal membranes that surrounds the baby in the womb during pregnancy are vital for normal development. Once the fetal membranes have ruptured or are damaged, they fail to heal leaving a defect until the end of pregnancy. Bacteria may subsequently ascend from the vagina into the womb, causing infection both to the fetus and mother. This condition is called pre-term premature rupture of the foetal membrane (PPROM), and is a common cause of preterm birth. PPROM also complicates 30% of fetal surgeries that are increasingly being used to treat abnormalities in the unborn baby such as spine, diaphragmatic and placental defects. However, PPROM and subsequent preterm birth compromises the outcome of treated babies, reducing the clinical effectiveness of foetal surgery. There are no clinical solutions to improve healing of the foetal membrane after it ruptures.

3D Printed Osteogenic & Hierarchal Bio Mineralizing Scaffold

The project will look to develop 3D printed polymeric scaffolds capable of acellular mineralization for enhancing integration of implants in maxillofacial applications.

Biomineralizing coatings for maxillofacial implants

The project aims to translate a mineralising coating that can be grown on 3D printed implants for bone augmentation of the mandibular area.

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.

Novel Cross-linking Strategy

This project focuses on the design of novel crosslinking strategies for silicone materials. These will enable the design of a new generation of silicone based composites with controlle mechanical properties and displaying conductive behaviour. The project will explore the use of these materials for 3D printing.