Characterisation of the role of canonical BMP-Smad 1/5/8 signalling in the development of ventral midbrain dopaminergic neurons

Ventral midbrain (VM) dopaminergic (DA) neurons, which project to the dorsal striatum via the nigrostriatal pathway, are progressively degenerated in Parkinson’s disease (PD). The identification of the instructive factors that regulate midbrain DA neuron development, and the subsequent elucidation of the molecular bases of their effects, is vital. Such an understanding would facilitate the generation of transplantable DA neurons from stem cells and the identification of developmentally-relevant neurotrophic factors, the two most promising therapeutic approaches for PD. Two related members of the bone morphogenetic protein (BMP) family, BMP2 and growth/differentiation factor (GDF) 5, which signal via a canonical Smad 1/5/8 signalling pathway, have been shown to have neurotrophic effects on midbrain DA neurons both in vitro and in vivo, and may function to regulate VM DA neuronal development. However, the molecular (signalling pathway(s)) and cellular (direct neuronal or indirect via glial cells) mechanisms of their effects remain to be elucidated. The present thesis hypothesised that canonical Smad signalling mediates the direct effects of BMP2 and GDF5 on the development of VM DA neurons. By activating, modulating and/or inhibiting various components of the BMP-Smad signalling pathway, this research demonstrated that GDF5- and BMP2-induced neurite outgrowth from midbrain DA neurons is dependent on BMP type I receptor activation of the Smad signalling pathway. The role of glial cell-line derived neurotrophic factor (GDNF)-signalling, dynamin-dependent endocytosis and Smad interacting protein-1 (Sip1) regulation, in the neurotrophic effects of BMP2 and GDF5 were determined. Finally, the in vitro development of VM neural stem cells (NSCs) was characterised, and the ability of GDF5 and BMP2 to induce these VM NSCs towards DA neuronal differentiation was investigated. Taken together, these experiments identify GDF5 and BMP2 as novel regulators of midbrain DA neuronal induction and differentiation, and demonstrate that their effects on DA neurons are mediated by canonical BMPR-Smad signalling.

Form-focused instruction in Irish-medium immersion education: a critical examination of teachers' perspectives and practices. A small-scale qualitative case study

It has been suggested that the less than optimal levels of students’ immersion language “persist in part because immersion teachers lack systematic approaches for integrating language into their content instruction” (Tedick, Christian and Fortune, 2011, p.7). I argue that our current lack of knowledge regarding what immersion teachers think, know and believe and what immersion teachers’ actual ‘lived’ experiences are in relation to form-focused instruction (FFI) prevents us from fully understanding the key issues at the core of experiential immersion pedagogy and form-focused integration. FFI refers to “any planned or incidental instructional activity that is intended to induce language learners to pay attention to linguistic form” (Ellis, 2001b, p.1). The central aim of this research study is to critically examine the perspectives and practices of Irish-medium immersion (IMI) teachers in relation to FFI. The study ‘taps’ into the lived experiences of three IMI teachers in three different IMI school contexts and explores FFI from a classroom-based, teacher-informed perspective. Philosophical underpinnings of the interpretive paradigm and critical hermeneutical principles inform and guide the study. A multi-case study approach was adopted and data was gathered through classroom observation, video-stimulated recall and semistructured interviews. Findings revealed that the journey of ‘becoming’ an IMI teacher is shaped by a vast array of intricate variables. IMI teacher identity, implicit theories, stated beliefs, educational biographies and experiences, IMI school cultures and contexts as well as teacher knowledge and competence impacted on IMI teachers’ FFI perspectives and practices. An IMI content teacher identity reflected the teachers’ priorities as shaped by pedagogical challenges and their educational backgrounds. While research participants had clearly defined instructional beliefs and goals, their roadmap of how to actually accomplish these goals was far from clear. IMI teachers described the multitude of choices and pedagogical dilemmas they faced in integrating FFI into experiential pedagogy. Significant gaps in IMI teachers’ declarative knowledge about and competence in the immersion language were also reported. This research study increases our understanding of the complexity of the processes underlying and shaping FFI pedagogy in IMI education. Innovative FFI opportunities for professional development across the continuum of teacher education are outlined, a comprehensive evaluation of IMI is called for and areas for further research are delineated.

Action design research: a comparison with canonical action research and design science

This research in progress paper addresses the IS issue in relation to conducting relevant research while keeping academic rigor. In particular, it contributes to the ongoing academic conversation around the investigation on how to incor-porate action in design science research. In this document the philosophical underpinnings of the recently proposed methodology called Action Design Re-search [1] are derived, outlined and integrated into Burrel and Morgan’s Par-adigmatic Framework (1979)[6]. The results so far show how Action Design Research can be considered as a particular case of Design Science Research (rather than a methodology closely related to Action Research) although they can assume two different epistemological positions. From these philosophical perspectives, future works will involve the inclusion of actual research projects using the three different methodologies. The final goal is to outline and structure the divergences and similarities of Action Design Research with Design Science Research and Canonical Action Research.