Following 4.5 years abroad I hope to work as a MSCA Fellow to tackle the issue of deleterious neuroinflammation following hypoxic injury in newborns. Hypoxic Ischemic Encephalopathy (HIE) describes brain injury that occurs when an infant’s brain does not receive enough oxygen & blood. Approximately 15-25% of patients die, 1 in 4 develop severe and permanent neurological disorders including, Cerebral Palsy & later-life Epilepsy. There are currently no successful treatment options & HIE has withstood attempts to improve outcome. A critical immune complex, the inflammasome was discovered in 2002 that senses ‘danger’ & processes potent inflammatory cytokines to bioactive forms. I have generated novel data demonstrating a role for the inflammasome & specifically targeting it for treatment of hypoxic brain injury. This study advances this by assessing the exact contribution of its activity on a cellular level & temporally targeting the complex as a novel treatment. I will employ established preclinical models of hypoxic brain injury, advanced imaging techniques (2- photon) & novel small molecule inhibitors of the complex. I will work at the Royal College of Surgeons in Ireland (RCSI) with supervisor Prof David Henshall, Director of the FutureNeuro Centre, a multi-institutional national centre for chronic & rare neurological disease research. Ultimately, our proposal will aid design & improvement of current clinical care strategies for infant patients with HIE. I will work with top neuroscientists within FutureNeuro & Europe (Prof Mallard, Sweden), the leading inflammasome company, Inflazome & its CSO Prof O’ Neill and Neonatologists including Prof Murray (Cork, Ireland). My collaboration with these leaders across multiple sectors will expand my competencies/transferable skills & allow advanced multidisciplinary training from experts. All of these will combine to leave me well-placed to provide meaningful contributions to Europe’s competitiveness and growth in the future.
Tissue engineered vascular grafts (TEVGs) hold great promise in the field of regenerative medicine and also possess the true potential to revolutionise the way in which clinicians treat the growing burden of cardiovascular disease. Treatment is achieved by incorporating an appropriate cell source onto a biodegradable scaffold and implanting the graft to bypass non-patent vascular segments. However, numerous issues regarding TEVG cell source render the technique unviable in a clinical setting as the cells require high levels of manipulation including digestion, isolation and culture. These issues increase processing costs, decrease cell stability and raise numerous regulatory issues. The use of minimally manipulated liposuction aspirate fluid (LAF) may offer a safer and more efficient cellular source in regenerative TEVGs. However, the capacity of LAF to act as a viable cell source for TEVGs is untested. The aim of this pr oject is to determine the capacity of LAF derived cells to act as a viable cell source for TEVGs. This will be achieved through characterisation of the LAF cells, investigation of the environment that best promotes favourable cellular behaviour, an in vivo study on the viability of the graft to act as a vascular interposition in a small animal model, scaling of the graft to appropriate human size and finally an in vivo study of the grafts ability to function as a vascular bypass in a large animal model. This fellowship will have an outgoing phase to Prof David Vorp’s Lab at the University of Pittsburgh and a return phase to Prof Fergal O’Brien’s Lab at the Royal College of Surgeons in Ireland. Having recently completed my PhD, which focused on the mechanical and morphological characterisation of human diseased vascular tissue, this fellowship will allow me to expand my existing repertoire of research and complementary skills to consolidate and build upon what I have learned to date as I evolve my independent, professional research career.
Biomaterials with antimicrobial properties which can be used for wound healing and tissue engineering applications offer high application potential due to the global increase of antimicrobial resistance. While polypeptides own this potential, their integration into a materials platform has not been realised to date. The overall objective of this project is to develop 3D printable antimicrobial or bacteriostatic polypeptide hydrogel materials, which can be employed in tissue regeneration applications to prevent bacterial growth. In particular, the goals include synthesis of sets of cross-linked polypeptide hydrogels based on lysine (Lys) and investigation of their hydrogel properties and 3D printability. Moreover, evaluation, validation and quantification of the antimicrobial properties of the hydrogels as well as the proof of concept demonstration for their feasibility in tissue regeneration will be addressed. The synthesis of these particular copolypeptides hydrogels is highly novel and their exploitation as a printable tissue regenerating platform is timely, of high fundamental as well as clinical impact and considered a new approach. The proposed project is broadly interdisciplinary, as disciplines of polymer chemistry, biomaterials science and engineering, microbiology and in vitro assessment techniques will be combined. The high-level science combined with complementary training will significantly advance the career opportunities of the applicant. Moreover, the excellent match of the applicant`s expertise with the project and the host organisation will ensure a strong transfer of knowledge between all participants. The potential of the proposed project is further highlighted by the possible commercial exploitation of the scientific findings and developments. Finally, it will enable new collaboration opportunities between research groups from different scientific fields.