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Oliver Hartley

Publications and source records attributed to Oliver Hartley.

20 records · Page 2Linked to original sources

The use of phage display in the study of receptors and their ligands.

Phage display technology presents a rapid means by which proteins and peptides that bind specifically to predefined molecular targets can be isolated from extremely complex combinatorial libraries. There are several important ways by which phage display can provide impetus to receptor-based research. Firstly, phage display can be applied, alongside transcriptome and proteome expression profiling techniques, to the identification and characterisation of receptors whose expression is specific to either a cell lineage, a tissue or a disease state. Secondly, specific monoclonal antibodies that enable researchers to identify, localize and quantify receptors can be produced very rapidly (weeks). Thirdly, it should be possible to apply phage display to the matching of orphan ligands and receptors. Finally, phage display can be used to identify proteins and peptides that modulate receptor activity. As well as being useful in the study of receptor function, biologically active proteins and peptides could also be used therapeutically, or as leads for drug design. Hence phage display is ready to play a central role in the study of receptors in the post-genome era. This review outlines the ways in which phage display has been applied to the study of receptor-ligand systems, and discusses how new developments in the technology may be of even greater utility to the field in the next decade.

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COPD results in a reduction in UCP3 long mRNA and UCP3 protein content in types I and IIa skeletal muscle fibers.

PURPOSE: Findings recently have shown coupling protein-3 (UCP3) content to be decreased in the skeletal muscle of patients with chronic obstructive pulmonary disease (COPD). Uncoupling protein-3 mRNA exists as two isoforms: long (UCP3L) and short (UCP3S). The UCP3 protein is expressed the least in oxidative and the most in glycolytic muscle fibers. Levels of UCP3 have been associated positively with intramyocellular triglyceride (IMTG) contents in conditions of altered fatty acid metabolism. As a source for muscle free fatty acid metabolism, IMTG is decreased in COPD. The current study completely characterized all the parameters of UCP3 expression (ie, UCP3L and UCP3S mRNA expression in whole muscle samples) and UCP3 protein content as well as IMTG content in the different fiber types in patients with COPD and healthy control subjects. METHODS: Using real-time polymerase chain reaction, UCP3 gene expression was quantified. Skeletal muscle fiber type and UCP3 protein and IMTG content were measured using immunofluorescence and Oil red oil staining, respectively. RESULTS: The findings showed that UCP3L mRNA expression was 44% lower (P < .005) in the patients with COPD than in the control subjects, whereas the UCP3S mRNA content was similar in the two groups. As compared with control subjects, UCP3 protein content was decreased by 89% and 83% and the IMTG content by 64% and 54%, respectively, in types I and IIa fibers (P < .0167) of patients with COPD, whereas they were unchanged in IIx fibers. CONCLUSIONS: The reduced UCP3 and IMTG content in the more oxidative fibers may be linked to the altered muscle fatty acid metabolism associated with COPD. Further studies are required to determine the exact role and clinical relevance of the reduced UCP3 content in patients with COPD.

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