David O’Connell's research while affiliated with University College Dublin and other places

... This in turn suggested that the integrity of the ribonucleoprotein particles is affected by calcium. This finding, together with the fact that intracellular calcium oscillations regulate critical steps in protein synthesis [13,14,28], prompted us to examine the relationship between calcium and RNP integrity in more detail. Rat brain RNPs are a population of heterogeneous size and density, so we first tested for gross changes in RNP structure by assessing sedimentation profiles in sucrose gradients in the presence and absence of calcium (Fig. 2C). ...

... Early and recent work has demonstrated the possibility to use cyclic peptides that could bind at protein-protein interface regions and interfere with protein-protein binding (Schreiber and Crabtree, 1992;Dechantsreiter et al., 1999;Sulyok et al., 2001;Shi et al., 2004;Zhang et al., 2014;Siegert et al., 2016;Shin et al., 2017). Identification of potential appropriate cyclic peptides can be achieved using techniques used in small-molecule drug design efforts such as virtual screening and pharmacophore matching approaches (Zhang et al., 2014;Duffy et al., 2015;Qian et al., 2017). In this study, we propose a straight forward automated process for the rapid search and optimization of cyclic peptides as protein-protein interaction inhibitors based on known structures of cyclic peptides. ...

... Similarly, in another work, QCM was also used to screen for nanoparticle binding to cells directly grown on the sensor surface (Gianneli et al., 2017). Another interesting approach to identify all epitopes exposed on the corona was reported by O'Connell et al. (2015), who FIGURE 4 | Mapping of receptor binding motifs on the biomolecular corona and identification of receptors mediating uptake by cells. Schematic illustration of epitope mapping of ApoB-100 on the biomolecular corona of SiO 2 nanoparticles by 5 nm immunogold nanoparticles conjugated with antibody anti-ApoB100 (A). ...

... Of these, 379 of the scFv antibodies were directed against 161 (mainly immunoregulatory) antigens. The remaining 15 scFv antibodies were directed against 15 short amino acid motifs (4−6 amino acids long), denoted CIMS antibodies 25 (Supporting Information Table S2). For some analytes, more than one scFv antibody clone (n = 2−9) targeting different epitopes was chosen to minimize the risk of impaired antibody activity followed by epitope masking during the sample labeling process. ...

... In keeping with lvPPA being associated with underlying AD pathology, the ndings of increased CCL2, CCL3 and CX3CL1 in this group parallel previous studies in those with a typical AD clinical presentation (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). CCL2 (MCP-1) is expressed by neurons, astrocytes and microglia, and has previously been shown to be raised in the CSF of people with typical AD including those with mild cognitive impairment (MCI) (14)(15)(16). ...

... Table 1) with confocal immunofluorescence for the distribution of plasma membrane-associated PHB and c-Kit at different clinical stages. For this analysis, we used the rhodamine-tagged peptide CKGGRAKDC, which is known to selectively bind PHB in adipose endothelial cells and the cell surface of drug-resistant lung cancer cells, [25,31,32] to stain for PHB in the membrane raft domain and Alexa 488 to stain for c-Kit. Our results showed that c-Kit and PHB colocalized in the membrane raft domain of ovarian serous carcinoma but not in normal ovarian tissue (Fig. 2a). ...

... Secretagogin is a Ca 2+ sensor protein ([Ca 2+ ] 0.5 is of ~25 µM for secretagogin in physiological salt buffers), which by definition induces protein-protein interactions through conformational change upon Ca 2+ binding followed by downstream signaling to control discrete cellular functions (Schwaller 2010). Secretagogin's in vitro interactome initially included synaptosomal-associated protein 25 kDa (SNAP-25) (Rogstam et al. 2007) with the more recent discovery of vesicle cargo, traffic and docking/release proteins (Bauer et al. 2011a,b, Romanov et al. 2015. Particularly, the 5th EF-hand domain can interact with cytoskeletal components (microtubules) (Maj et al. 2010, Yang et al. 2016. ...

... Secretagogin-positive cells are often found in vicinity to the ventricular system with dendrites oriented along the pial surface, which might display a role in releasing neuroactive substances into the cerebrospinal fluid (Mulder et al., 2009(Mulder et al., , 2010. Further assumed functions are a neuroendocrine role in vesicle exocytosis (Bauer et al., 2011), microtubules dynamics (Maj et al., 2010(Maj et al., , 2012, and a possible neuroprotective role against the neurodegeneration as in Alzheimer disease (Attems et al., 2008). Altered secretagogin expression has been described to possibly reflect cellular dysfunction of locus coeruleus neurons in Alzheimer disease (Zahola et al., 2019). ...

... The interactions among CRAC2A and STIM1 or Orai1 involve the coiled-coil domain, as well as the proline/lysine rich segment of the former, and considering Orai1, map to the N-terminal domain with K85 and K87 serving as critical interaction sites (Figure 1) [21]. It is worth mentioning that the sites of CRACR2A-STIM1 and CRACR2A-Orai1 interaction overlap with these described to bind calmodulin (CaM) in the presence of Ca 2+ , explicitly including hOrai1 and the lysin-rich domain of hSTIM1 [21,83]. CRAC2A associations with both basic components of the CRAC channel complex are associated with a stringent dependence on the activation state, as these are promoted successively to store depletion yet exclusively under Ca 2+ -free conditions, while otherwise strong binding between the mentioned domains of STIM1/Orai1 and CRACR2A was reported to vanquish if exposed to buffer solutions supplemented with 2 mM Ca 2+ [21]. ...

... Protein gel electrophoresis is a standard method for studying protein interaction to NP. For example, an earlier study demonstrated the presence of transferrin and/or human serum albumin on the surface of polystyrene nanoparticles were effectively analyzed using SDS-PAGE [18]. SDS-PAGE was also used to compare the amount of proteins adsorbed on gold nanoparticles [19]. ...