The proportion of people around the world aged over 60 years is growing faster than any other age group, as a result of longer life expectancy. This population ageing can be seen as a success story for public health policies and for socioeconomic development, but it places a challenge on medicine and, within the UK, the NHS to maximize the health and functional capacity of older people. Regenerative Medicine is one potential solution for this longer life and healthy lifestyle, providing cell based therapies which can replace damaged or diseased tissues. Growing replacement tissues is bringing exciting novel solutions which now require new manufacturing methods and processes to enable the translation to the clinic. Bioreactors are mechanical devices that provide controlled growth environments for engineered tissues and mimic the physical forces cells and tissues experience in the body. Monitoring the maturation of tissue implants during culture, and prior to implantation into the patient, is important for defining optimum manufacturing criteria and for their clinical success. Key properties that tissue engineered implants must display include strength and durability. To infer material properties from imaging, new non-destructive, three-dimensional imaging techniques are needed, that can be used to provide accurate results efficiently at both the manufacturing site and the clinic. In this proposal, our partners have linked the imaging technique, optical coherence elastography, with a hydrostatic pressure bioreactor to create a novel imaging solution, MechAscan, which allows real-time mechanical characterisation and simultaneous physical stimulation of engineered tissue implants. MechAscan will provide a clear advantage over currently available traditional mechanical testing approaches and elastography techniques, which require direct contact of the mechanical load with the sample and are destructive. Additionally, MechAscan can be used for real-time monitoring of mechanical properties as the construct is grown in culture in a sterile growth environment. Our aim is to develop a novel technology platform allowing real-time and non-destructive monitoring of tissue engineered products in a sterile growth environment to avoid construct to construct variation during manufacturing and allow the translation of regenerative medicine constructs with known properties into the clinic. To facilitate uptake in use of the technology and translation to the clinic, we propose to fully test and validate the MechAscan technology in an interdisciplinary approach combining bioreactor technology, biomaterials science, physics and mathematics.

Neurodegenerative diseases, such as Parkinson’s disease, are a major public health issue given the aging population in Europe and beyond. While curative pharmacological treatment of these diseases is not in sight, cell replacement therapies (CTs) are considered very promising, in particular with the advent of stem-cell reprogramming technologies. However, a fundamental challenge in the medical application of CTs in the brain of patients lies in the lack of control of cell behaviour at the site of transplantation, and particularly their differentiation and oriented growth. The aim of this project is to introduce a fundamentally new concept for remote control of cellular functions by means of magnetic manipulation. The technology is based on magnetic nanoparticles functionalized with proteins involved in cellular signalling cascades. These biofunctionalized MNPs (bMNPs) will be delivered into target cells, where they act as intracellular signalling platforms activatable in a spatially and temporally controlled manner by external magnetic fields. The project will focus on engineering these tools for the control of neuronal cell programming and fibre outgrowth by hijacking Wnt and neurotrophin signalling, respectively, with the ulti-mate objective of advancing cell replacement therapies for PD using dopaminergic precursor neurons. To achieve this ambitious goal, we have gathered an interdisciplinary consortium interfacing scientists having cutting-edge know-how in bMNP engineering, surface functionalization and cellular nanobiophysics with renowned experts in neuronal cell differentiation, stem-cell reprogramming and regenerative (nano-)medicine. By exploiting this complementary expertise, a novel, versatile technology for magnetic control of intracellular signalling is envis-aged, which will be a breakthrough for remote actuation of cellular functions and its successful implementation in CTs for neurodegenerative diseases and injuries within the following decade.

The proposed research has a thematic strand (1) and a methods strand (2), as outlined below: 1) It looks at representations of Quebec's 'regions'--spaces and places outside Montreal--in post-1960 fiction in French and English. From the period of modern day nationalist assertion popularly dated as beginning in 1960 until around 10 years ago, 'hors-Montreal' (rest of Quebec, or ROQ) was marginalised in terms of literary production and criticism, as well as cultural and political debates. What became known as Quebec's Quiet Revolution sought to effect a break with the past, rejecting a pan-Canadian cultural nationalism in favour of a territorial nationalism which cast Quebec as the sole francophone 'home' within Canada. Symbol of a new, modern Quebec nation, Montreal increasingly became the preferred setting for fiction (Nepveu and Marcotte 1992, 7) and literary criticism. With the exception of a small handful of works (e.g. Laforest 2016, 2010; Sing 1995; Warwick 1968), analyses of literary representations of spaces and places outside of Quebec's main city were relegated to the occasional book chapter. Since 2000, however, 'hors-Montreal' has attracted renewed public interest with respect to politics and culture. In literature, Montreal is being displaced as authors increasingly opt to set their novels in smaller cities, villages, rural and 'wilderness' spaces (Archibald 2012, 17). Whilst this is particularly true of French-language authors, some English-language fiction on and of 'the regions' exists (e.g. Penny, Keightley). Looking beyond the discipline of Quebec Studies, the project considers trends in 'new regional writing' in the UK and North America (e.g. New Writing North). It also explores wider questions around the relationships between the urban and non-urban, the city and 'regions'. Writing in 1973, Raymond Williams argued that the boundaries between the country and the city were not clear-cut (1975 (1973): 1). Debates within rural geography (Cloke 2006, Edensor 2006) highlight the ways in which such boundaries are increasingly blurred, partly due to globalisation. 'The regions' have, of course, asserted themselves in recent years in other places besides Quebec, notably in the UK referendum on membership of the European Union (2016) and the U.S presidential elections (2016). 2) The project aims to draw on, and develop further 'walking studies' (Lorimer 2011, Morgan 2016) methods and methodologies on which I have been working since 2014, and which belong to the subdiscipline of Geohumanities. Broadly conceived, Geohumanities brings together spatial concerns in Humanities and Social Sciences. Creativity is often used to facilitate exchange and participation (see, e.g. Cresswell 2015: 7). 'Heartlands/pays du coeur' draws on methods from literary geographies, geopoetics, psychogeography and other walking, writing and creative practices, combining these with methods from oral history and geography. It will produce and co-produce a variety of knowledge forms. These include academic outputs such as a journal article and conference papers, and non-academic outputs like creative writing texts (where 'writing' encompasses a variety of practices, not all of them word-based), readings, a dance, a digital map and an audio-walk. In terms of future legacies, the project will serve as preparation for leading an inter- and multi- disciplinary project on walking (defined as a range of practices, some of which are bipedal), well-being and regions.

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