ERC FUNDED PROJECTS

1.2 billion people worldwide lack access to safe drinking water. Drinking water quality is threatened by newly emerging organic micro-pollutants (pesticides, pharmaceuticals, industrial chemicals) in source waters. Nanofiltration is a technology that is expected to play a key role in future water treatment processes due to its effectiveness in removal of micropollutants. However, the loss of membrane flux due to fouling is one of the main impediments in the development of membrane processes for use in drinking water treatment. Currently there is a wholly inadequate mechanistic understanding of the role of biofilm on the fouling of nanofiltration membranes. Applying techniques including confocal microscopy, force spectroscopy, and infrared spectroscopy using an experimental programme informed by a technique known as scale-down together with mathematical modelling, it is confidently expected that significant advances will be gained in the mechanistic understanding of nanofiltration biofouling. The specific objectives are 1. How is the rate of formation and extent of such biofilms influenced by the biological response to the local microenvironment? 2 Elucidate the effect of extracellular polysaccharide substances on physical properties, composition and structure of these biofilms. 3: Investigate mechanisms to enhance biofilm removal by a physical detachment process complemented by techniques that alter biofilm material properties. A more fundamental insight into the mechanisms of nanofiltration operation will help in further development of this treatment method in future water treatment processes.

1 468 987 €

Start date: 2011-10-01, End date: 2016-09-30

This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation. Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact. This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.

1 372 135 €

Start date: 2017-10-01, End date: 2022-09-30

Every 30 seconds a person suffers an osteoporosis-related bone fracture in the EU, resulting in significant morbidity, mortality, and health-care costs estimated at €36billion annually. Current therapeutics target bone resorbing osteoclasts, but these are associated with severe side effects. Osteoporosis arises when mesenchymal stem cells (MSC) fail to produce sufficient numbers of bone forming osteoblasts. A key regulator of MSC behaviour is physical loading, yet the mechanisms by which MSCs sense and respond to changes in their mechanical environment are virtually unknown. Primary cilia are nearly ubiquitous ‘antennae-like’ cellular organelles that have very recently emerged as extracellular mechano/chemo-sensors and thus, are strong candidates to play a role in regulating MSC responses in bone. Therefore, the objective of this research program is to determine the role of the primary cilium and associated molecular components in the osteogenic differentiation and recruitment of human MSCs in loading-induced bone adaptation. This will be achieved through ground-breaking in vitro and in vivo techniques developed by the applicant. The knowledge generated in this proposal will represent a profound advance in our understanding of stem cell mechanobiology. In particular, the identification of the cilium and associated molecules as central to stem cell behaviour will lead to the direct manipulation of MSCs via novel cilia-targeted therapeutics that mimic the regenerative influence of loading at a molecular level. These novel therapeutics would therefore target bone formation, providing an alternative path to treatment, resulting in an improved supply of bone forming cells, preventing osteoporosis. Furthermore, these novel therapeutics will be incorporated into biomaterials, generating bioactive osteoinductive scaffolds. These advances will not only improve quality of life for the patient but will significantly reduce the financial burden of bone loss diseases in the EU.

1 455 068 €

Start date: 2013-11-01, End date: 2018-10-31

Corneal blindness resulting from disease, physical injury or chemical burns affects millions worldwide and has a considerable economic and social impact on the lives of people across Europe. In many cases corneal transplants can restore vision however the shortage of donor corneas suitable for transplantation has necessitated the development of alternative treatments. The aim of this project is to develop a new approach to corneal tissue regeneration. Previous approaches at engineering corneal tissue have required access to donor cells and lengthy culture periods in an attempt to grow tissue in vitro prior to implantation with only limited success and at great expense. Our approach will differ fundamentally from these in that we will design artificial corneal scaffolds that do not require donated cells or in vitro culture but instead will recruit the patient’s own cells to regenerate the cornea post-implantation. These biomaterial scaffolds will incorporate specific chemical and physical cues with the deliberate aim of attracting cells and inducing tissue formation. Studies will be undertaken to examine how different chemical, biochemical, physical and mechanical cues can be used to control the behaviour of corneal epithelial, stromal and endothelial cells. Once the optimal combination of these cues has been determined, this information will be incorporated into the design of the scaffold. Recent advances in manufacturing and material processing technology will enable us to develop scaffolds with organized nanometric architectures and that incorporate controlled growth factor release mechanisms. Techniques such as 3D bio-printing and nanofiber electrospinning will be used to fabricate scaffolds. The ability of the scaffold to attract cells and promote matrix remodelling will be examined by developing an in vitro bioreactor system capable of mimicking the ocular environment and by performing in vivo tests using a live animal model.

1 498 734 €

Start date: 2015-07-01, End date: 2020-06-30