Research Repository

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Structural basis of the leukocyte integrin Mac-1 I-domain interactions with the platelet glycoprotein Ib (2019)
Journal Article
Morgan, J., Saleem, M., Ng, R., Armstrong, C., Wong, S. S., Caulton, S. G., …Emsley, J. (2019). Structural basis of the leukocyte integrin Mac-1 I-domain interactions with the platelet glycoprotein Ib. Blood Advances, 3(9), 1450-1459. doi:10.1182/bloodadvances.2018027011

Cell-surface receptor interactions between leukocyte integrin macrophage-1 antigen (Mac-1, also known as CR3, aMb2, CD11b/CD18) and platelet glycoprotein Iba (GPIba) are critical to vascular inflammation. To define the key residues at the binding inter... Read More

ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling (2016)
Journal Article
Goode, A., Rea, S., Sultana, M., Shaw, B., Searle, M. S., & Layfield, R. (2016). ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling. Molecular and Cellular Neuroscience, 76, doi:10.1016/j.mcn.2016.08.004

The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of ne... Read More

Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin (2016)
Journal Article
Scott, D., Garner, T. P., Long, J., Strachan, J., Mistry, S. C., Bottrill, A. R., …Layfield, R. (in press). Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin. Proteomics, 16(14), doi:10.1002/pmic.201600067

Unanchored polyubiquitin chains are emerging as importanregulators of cellular physiology with diverse roles paralleling those of substrate-conjugated polyubiquitin. However tools able to discriminate unanchored polyubiquitin chains of different isop... Read More

Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD (2016)
Journal Article
Goode, A., Butler, K., Long, J., Cavey, J., Daniel, S., Shaw, B., …Layfield, R. (2016). Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD. Autophagy, 12(7), 1094-1104. https://doi.org/10.1080/15548627.2016.1170257

Growing evidence implicates impairment of autophagy as a candidate pathogenic mechanism in the spectrum of neurodegenerative disorders which includes amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS-FTLD). SQSTM1, which encode... Read More

SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance (2016)
Journal Article
Asiani, K. R., Williams, H. E. L., Bird, L., Jenner, M., Searle, M. S., Hobman, J. L., …Soultanas, P. (2016). SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance. Molecular Microbiology, 101(5), 731-742. https://doi.org/10.1111/mmi.13399

Ag+ resistance was initially found on the Salmonella enetrica serovar Typhimurium multi-resistance plasmid pMG101 from burns patients in 1975. The putative model of Ag+ resistance, encoded by the sil operon from pMG101, involves export of Ag+ via an... Read More

Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells (2016)
Journal Article
Cini, M., Williams, H. E. L., Fay, M. W., Searle, M., Woodward, S., & Bradshaw, T. D. (2016). Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells. Metallomics, doi:10.1039/C5MT00297D

Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure T... Read More

A Targeted Oligonucleotide Enhancer of SMN2 Exon 7 Splicing Forms Competing Quadruplex and Protein Complexes in Functional Conditions (2014)
Journal Article
Smith, L., Dickinson, R., Lucas, C., Cousins, A., Malygin, A., Weldon, C., …Eperon, I. (2014). A Targeted Oligonucleotide Enhancer of SMN2 Exon 7 Splicing Forms Competing Quadruplex and Protein Complexes in Functional Conditions. Cell Reports, 9(1), 193-205. doi:10.1016/j.celrep.2014.08.051

The use of oligonucleotides to activate the splicing of selected exons is limited by a poor understanding of the mechanisms affected. A targeted bifunctional oligonucleotide enhancer of splicing (TOES) anneals to SMN2 exon 7 and carries an exonic spl... Read More

A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa (2014)
Journal Article
Kulkarni, P. R., Jia, T., Kuehne, S. H., Kerkering, T. M., Morris, E. R., Searle, M. S., …Kulkarni, R. V. (in press). A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa. Nucleic Acids Research, 42(11), doi:10.1093/nar/gku309

CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such as secondary metabolism, motility, biofilm formation and the p... Read More

Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function (2014)
Journal Article
Goode, A., Long, J. E., Shaw, B., Ralston, S. H., Visconti, M. R., Gianfrancesco, F., …Layfield, R. (2014). Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function. BBA - Molecular Basis of Disease, 1842(7), 992-1000. doi:10.1016/j.bbadis.2014.03.006

SQSTM1 mutations are common in patients with Paget disease of bone (PDB), with most affecting the C-terminal ubiquitin-associated (UBA) domain of the SQSTM1 protein. We performed structural and functional analyses of two UBA domain mutations, an I424... Read More