Leader's reflections on knowledge, knowing and not knowing: an analysis of change over time

One commonality across the leadership and knowledge related literature is the apparent neglect of the leaders own knowledge. This thesis sought to address this issue through conducting exploratory research into the content of leader’s personal knowledge and the process of knowing it. The empirical inquiry adopted a longitudinal approach, with interviews conducted at two separate time periods with an extended time-interval between each. The findings from this research contrast with images of leadership which suggest leaders are in control of what they know, that they own their own knowledge. The picture that emerges is one of individuals struggling to keep abreast of the knowledge required to deal with the dynamics and uncertainties of organisational life. Much knowledge is tacit, provisional and perishable and the related process of knowing more organic, evolutionary and informal than any structured or orchestrated approach. The collective nature of knowing is a central feature, with these leaders embedded in networks of uncontrollable relationships. In view of the indeterminate nature of knowing, the boundary between what is known and what one needs to know is both amorphous and ephemeral, and the likelihood of knowledge-absences is escalated. A significant finding in this regard is the identification of two critical points where not-knowing is most likely (entry and exit from role) and the differing implications of each. Overtime the knowledge that is legitimised or prioritised is significantly altered as these leaders replace the dogmas that were previously held in high esteem with the lessons from their own experience. This experience brings increased self-knowledge and a deeper appreciation of the values and morals instilled in their early lives. In view of the above findings, this study makes theoretical contribution to a number of core literatures: authentic leadership, role transition and knowledge-absences. In terms of leadership development, the findings point to the necessity to prepare leaders for the challenges they will encounter at the pivotal stages of the leadership role.

Recoding: reprogrammed genetic decoding with an emphasis on antizyme regulatory frameshifting

Recoding embraces mechanisms that augment the rules of standard genetic decoding. The deviations from standard decoding are often purposeful and their realisation provides diverse and flexible regulatory mechanisms. Recoding events such as programed ribosomal frameshifting are especially plentiful in viruses. In most organisms only a few cellular genes are known to employ programed ribosomal frameshifting in their expression. By far the most prominent and therefore well-studied case of cellular +1 frameshifting is in expression of antizyme mRNAs. The protein antizyme is a key regulator of polyamine levels in most eukaryotes with some exceptions such as plants. A +1 frameshifting event is required for the full length protein to be synthesized and this requirement is a conserved feature of antizyme mRNAs from yeast to mammals. The efficiency of the frameshifting event is dependent on the free polyamine levels in the cell. cis-acting elements in antizyme mRNAs such as specific RNA structures are required to stimulate the frameshifting efficiency. Here I describe a novel stimulator of antizyme +1 frameshifting in the Agaricomycotina class of Basidiomycete fungi. It is a nascent peptide that acts from within the ribosome exit tunnel to stimulate frameshifting efficiency in response to polyamines. The interactions of the nascent peptide with components of the peptidyl transferase centre and the protein exit tunnel emerge in our understanding as powerful means which the cell employs for monitoring and tuning the translational process. These interactions can modulate the rate of translation, protein cotranslational folding and localization. Some nascent peptides act in concert with small molecules such as polyamines or antibiotics to stall the ribosome. To these known nascent peptide effects we have added that of a stimulatory effect on the +1 frameshifting in antizyme mRNAs. It is becoming evident that nascent peptide involvement in regulation of translation is a much more general phenomenon than previously anticipated.

Regulation of tail-anchored ubiquitin conjugating enzymes that are localised to the endoplasmic reticulum

The vast majority of secreted and membrane proteins are translated and folded at the endoplasmic reticulum (ER), where a sophisticated quality control mechanism ensures that only correctly folded proteins exit the ER and traffic to their final destinations. On the other hand, proteins that persistently misfold are eliminated through a process known as ER associated degradation (ERAD). This involves retrotranslocation of the misfolded protein through the ER membrane, and ubiquitination in advance of degradation by cytosolic proteasomes. The process of ERAD is best described in yeast where ubiquitin conjugating enzymes Ubc6p and Ubc7p function with a limited number of E3 ubiquitin ligases to ubiquitinate misfolded proteins. Interestingly, although the mechanistic principles of ERAD have been conserved through evolution, there is increasing evidence that homologues of the yeast enzymes have gained divergent roles and novel regulatory functions in higher eukaryotes, meaning that the process in humans is more complex and involves a larger repertoire of participating proteins. Two homologues of Ubc6p have been described in humans, and have been named as Ubc6 (UBE2J2) and Ubc6e (UBE2J1). However, little work has been done on these enzymes and thus our main objective of this study was to progress the functional characterisation of these ERAD E2 conjugating enzymes. Our studies included a detailed analysis of conditions whereby these proteins are stabilised and degraded. We’ve also explored the different molecular signalling pathways that induced changes on their steady state protein levels. Furthermore, Ubc6e has a phosphorylatable serine residue at position 184. Thus, our studies also involved delineating the signalling kinases that phosphorylate Ubc6e and examining its function in ERAD. Our studies confirm that the E2 Ubc enzymes are regulated posttranslationally and may have important implications in the regulation of ERAD.

The EU referendum in Northern Ireland: closing borders, re-opening border debates

The UK decision to leave the European Union (EU) following a referendum in June 2016 fundamentally alters the country's relationship with the EU, with its European neighbours, with the rest of the world and potentially with its own constituent units. It is clear that different parts of the UK will be impacted differently by this decision and by the unfolding exit terms and process. In this context, Northern Ireland is considered to be particularly vulnerable. This article examines the referendum campaign in Northern Ireland by detailing input from the Northern Ireland administration, political parties, civil society and external figures. The article suggests that the overall referendum campaign in Northern Ireland was hamstrung by the opposing positions taken by key political protagonists, particularly Sinn Féin and the Democratic Unionist Party (DUP). This produced a challenging context for the referendum debate in Northern Ireland. The post-referendum period has also been marked by persistent differences in relation to how best to approach specific Northern Ireland issues and challenges. A continued absence of clear positions and a lack of contingency planning underline a poor level of preparedness for future political developments.