Visualising ribosome profiling and using it for reading frame detection and exploration of eukaryotic translation initiation

Ribosome profiling (ribo-seq) is a recently developed technique that provides genomewide information on protein synthesis (GWIPS) in vivo. The high resolution of ribo-seq is one of the exciting properties of this technique. In Chapter 2, I present a computational method that utilises the sub-codon precision and triplet periodicity of ribosome profiling data to detect transitions in the translated reading frame. Application of this method to ribosome profiling data generated for human HeLa cells allowed us to detect several human genes where the same genomic segment is translated in more than one reading frame. Since the initial publication of the ribosome profiling technique in 2009, there has been a proliferation of studies that have used the technique to explore various questions with respect to translation. A review of the many uses and adaptations of the technique is provided in Chapter 1. Indeed, owing to the increasing popularity of the technique and the growing number of published ribosome profiling datasets, we have developed GWIPS-viz (http://gwips.ucc.ie), a ribo-seq dedicated genome browser. Details on the development of the browser and its usage are provided in Chapter 3. One of the surprising findings of ribosome profiling of initiating ribosomes carried out in 3 independent studies, was the widespread use of non-AUG codons as translation initiation start sites in mammals. Although initiation at non-AUG codons in mammals has been documented for some time, the extent of non-AUG initiation reported by these ribo-seq studies was unexpected. In Chapter 4, I present an approach for estimating the strength of initiating codons based on the leaky scanning model of translation initiation. Application of this approach to ribo-seq data illustrates that initiation at non-AUG codons is inefficient compared to initiation at AUG codons. In addition, our approach provides a probability of initiation score for each start site that allows its strength of initiation to be evaluated.

A history of the Irish Red Cross Society, 1939-1971

This research is concerned with assessing from a national perspective the role, work and historical impact of the Irish Red Cross Society (IRCS) between 1939 and 1971. During this period the IRCS discharged three primary functions: it provided first aid services both in war-time and peace-time; it pioneered public health and social care services; and acted as the State’s main agency for international humanitarian relief measures. Although primarily a national organisational history of the Society, it is not a history in isolation. A broader perspective demonstrates that the work undertaken by the IRCS has relevance to the medical, social, religious, cultural, political and diplomatic history of twentieth century Ireland. This study assesses the impact of a number of significant public health and social care initiatives which the IRCS implemented and developed since its inception and how most of these were subsequently developed independently by the State. During the early 1940s, the Society’s formation of a national blood transfusion service ultimately laid the foundations for the establishment of a national blood transfusion service. The Society’s steering of a national anti-tuberculosis campaign in the 1940s brought the issue of the eradication of TB to the fore and helped to change public attitudes towards the disease. The concept of caring for the needs of the elderly in Ireland was largely unknown until the IRCS began addressing the issue in the 1950s and, for more than two decades, was effectively the only organisation in the State that campaigned and introduced innovative services for the aged. The IRCS made a significant impact in terms of its commitment to the needs of refugees and the provision of international humanitarian relief from Ireland. The Society’s donation in 1945 of a fully equipped hospital to the population of Saint-Lo in France, its war-time overseas relief efforts and its post-war work for child refugees earned Ireland significant international recognition and prestige and, more importantly, justified Ireland’s war-time policy of neutrality. With Ireland’s admission to the UN, the government became more dependent on the IRCS to consolidate that position.