The awarding of the first honorary Doctor of Science by the Queen's University in Ireland to William King – a journey of scientific curiosity

William King (1809 86) was the founding Professor of Mineralogy and Geology at Queen s College Galway (QCG), one of three regional colleges opened in 1849 to provide secular university-level education in Ireland. King came from a modest background and despite lacking third-level qualifications, began publishing on palaeontological and geological matters in the 1840s. These early contributions aided his application for the professorship in Galway, particularly his seminal 1850 monograph on the Permian fossils of England, which was in preparation at the time. During his first two decades at QCG, King maintained an up-to-date teaching programme in geology and palaeontology, played a key role in establishing the natural history museum and further developed his research portfolio. He investigated several topics of international interest, including the supposed earliest fossils of living organisms and the emerging evidence for fossil humans. King s achievements were impressive, particularly as he was essentially self-taught and also considering the isolated and poor economic standing of Galway at the time. The Queen s University in Ireland (QUI) bestowed its first ever honorary Doctor of Science on William King in 1870 in recognition of his distinguished geological research, and also to mark a refocussing of the university curriculum to better reflect the importance of science. King s award came at a time when the education system was coming under increasing scrutiny in Ireland, and as part of these reforms QUI was dissolved in 1882 and replaced by the Royal University of Ireland. One of the final acts of QUI was to award a large number of former graduates with master s degrees. A select few were conferred with honorary doctorates, including King s eldest son, William Jr., who had been amongst the first students to enter QCG in 1849 and, after graduating, enjoyed a distinguished career with the Geological Survey of India. Father and son thus achieved the unique honour of being the first and last recipients of a Doctor of Science (honoris causa) from QUI for their geological endeavours.peer-reviewe

Interactions of human Cdc45 with the Mcm2-7 complex, the GINS complex, and DNA polymerases delta and epsilon during S phase.

Cdc45 is an essential cellular protein that functions in both the initiation and elongation of DNA replication. Here, we analyzed the localization of human Cdc45 and its interactions with other proteins during the cell cycle. Human Cdc45 showed a diffuse distribution in G1 phase, a spot-like pattern in S and G2, and again a diffuse distribution in M phase of the cell cycle. The co-localization of Cdc45 with active replication sites during S phase suggested that the human Cdc45 protein was part of the elongation complex. This view was corroborated by findings that Cdc45 interacted with the elongating DNA polymerases delta and epsilon, with Psf2, which is a component of the GINS complex as well as with Mcm5 and 7, subunits of the putative replicative DNA helicase complex. Hence, Cdc45 may play an important role in elongation of DNA replication by bridging the processive DNA polymerases delta and epsilon with the replicative helicase in the elongating machinery

Multiple roles for kinases in DNA replication

DNA replication is carried out by the replisome, which includes several proteins that are targets of cell-cycle-regulated kinases. The phosphorylation of proteins such as replication protein A, DNA polymerase-α and -δ, replication factor C, flap endonuclease 1 and DNA ligase I leads to their inactivation, suggesting that phosphorylation is important in the prevention of re-replication. Moreover, the phosphorylation of several of these replication proteins has been shown to block their association with the 'moving platform'—proliferating cell nuclear antigen. Therefore, phosphorylation seems to be a crucial regulator of replisome assembly and DNA replication, although its precise role in these processes remains to be clarified

Integrated stoichiometric, thermodynamic and kinetic modelling of steady state metabolism

The quantitative analysis of biochemical reactions and metabolites is at frontier of biological sciences. The recent availability of high-throughput technology data sets in biology has paved the way for new modelling approaches at various levels of complexity including the metabolome of a cell or an organism. Understanding the metabolism of a single cell and multi-cell organism will provide the knowledge for the rational design of growth conditions to produce commercially valuable reagents in biotechnology. Here, we demonstrate how equations representing steady state mass conservation, energy conservation, the second law of thermodynamics, and reversible enzyme kinetics can be formulated as a single system of linear equalities and inequalities, in addition to linear equalities on exponential variables. Even though the feasible set is non-convex, the reformulation is exact and amenable to large-scale numerical analysis, a prerequisite for computationally feasible genome scale modelling. Integrating flux, concentration and kinetic variables in a unified constraint-based formulation is aimed at increasing the quantitative predictive capacity of flux balance analysis. Incorporation of experimental and theoretical bounds on thermodynamic and kinetic variables ensures that the predicted steady state fluxes are both thermodynamically and biochemically feasible. The resulting in silico predictions are tested against fluxomic data for central metabolism in Escherichia coli and compare favourably with in silico prediction by flux balance analysis.National University of Ireland, Galway, Science Faculty Fellowship. I.T. was supported by NIH grant Grant 5R01GM057089-11.Deposited by bulk impor