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.

A Biophysical Model of Gum Reintegration on enamel

Organ-on-a-chip Centre of Excellence

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).

UKRMP2 Acellular / Smart Materials

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.

Organ-on-a-Chip Technologies

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

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.

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.

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.

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.

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.

Biomechanical determinants of advanced coronary atherosclerotic plaque formation in transgenic hyperlipidaemic minipigs

Sensory and Supporting Cells in the Organ of Corti

The aim of this project is to study force transmisison within the cochlea as it is mechanically stimulated by sound. This programme grant is lead by Brighton U. and features a combination of experimental approaches and novel modelling analysis. Our lab uses AFM to mechanically characterize speciallized cells in the cochlea, so that mechanical parameters can be fed into new models.

THaCH - The effects of hypercholesterolemia on tendon health

Musculoskeletal diseases cause pain and suffering to millions of people worldwide. This proposal aims to significantly enhance our understanding of hypercholesterolemia on aspects of tendon health, a highly under-researched area and one of significant clinical importance. The findings from the proposed research are likely to have major implications for orthopedic sciences and preventative medicine as well as rehabilitation services, strategies and technology. Such knowledge has the potential to improve quality of life and reduce socio-economic costs associated with the disability resulting from orthopedic and musculoskeletal diseases.

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.

Supramolecular peptide nanotechnology for antimicrobial therapies

Antimicrobials remain the main means to treat and control bacterial infections. Their efficacy is now compromised due to overuse in humans, animals, agriculture, with bacteria developing resistance that renders certain antibiotics ineffective. Infections due multi-drug resistant (MDR) bacteria have emerged as one of the most significant global threats to human and animal health in the 21st century. Thus, the development of new antibiotics, or better ways to deliver conventional antibiotics more effectively, is an urgent priority. This project is focused on the formulation and assessment of novel self-assembled peptide nanocarriers, able to restore and/or enhance the activity of known antibiotics against MDR bacteria.

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

Investigation of chemotaxis in modulating smart behaviour in synthetic bone graft substitutes

Silicate substituted apatite bone grafts have an enhanced capacity to stimulate bone regeneration. Moreover, altering the level of strut porosity has the capacity to confer osteoinductive behaviour to these graft materials. The aim of this project is to investigate whether these phenomena are related to more efficient cell recruitment and tasking, through (i) exchange of Ca, PO4 and SiO4 ions, and/or (ii) optimal sequestering and enrichment of native signalling molecules.

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 ...

Thin polymer films and surface functionalisation chemistry.

Polymer thin films are being coated on optically active silver and gold nanoparticles for hand held biosensing.

Mechno-regulation of genome function to direct stem cell rate

Mechno-regulation of genome function to direct stem cell rate

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.

Impact of Physiogel on tribological properties and structural integrity of the skin

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.