AbstractBackgroundThis year the scientific committee has examined abstract submissions for evidence of User Involvement that is,▶Present from the early stages of the research cycle (eg, generating ideas, prioritising, study design).▶Collaborative – working as co-researchers – not simply commenting on completed work.▶Innovative – (eg, presenting to funding/ethics boards undertaking interviews, leading dissemination in some areas).▶And has created a tangible output which has contributed to the conduct of the study (eg, protocol writing, higher recruitment, richer data).AimsTo highlight and acknowledge those researchers who have demonstrated a high level of commitment to User Involvement in their work.To emphasise the importance of collaborating with service users in research and to offer some insight into the future of User Involvement in SUPAC research.MethodsProfessor David Cameron, Clinical Director at the Edinburgh Cancer Research Centre and former Director of NCRN, will reflect on the significance of User Involvement during his time at NCRN and offer some personal insight into how best SUPAC research might flourish. Following this talk, three shortlisted candidates for this year's User Involvement Award will take part in a short discussion about their work, following which a presentation will be made to the winner.
Lipodepsipeptides (LPDs) are a group of cyclic, acylated peptides produced by several Pseudomonas species. They are usually divided in two groups, mycins and peptins, on the basis of the size of the amino acidic part of the molecule. Mycins have a ring of 9 amino acids closed between the first and the last residue, peptins contain a more complex peptide moiety of up to 25 amino acids, partially cyclized. Both mycins and peptins attack the plasma membrane, but may have different target organisms. Comparing the mode of action of these two classes of LDPs on natural and model membranes we observed that all peptides induced red blood cell haemolysis and leakage of tonoplasts and liposornes by the formation of pores. The haemolytic activity of the smaller mycins was higher than that of the bigger peptins and proportional to the amphipathic index of the molecule. The extent of permeabilization was dependent also on the composition of the lipid membrane. In particular, mycins show a preference for sterols, whereas peptins are more active on phospholipids, especially sphingomyelin. These differences may have physiological implications. The formation of discrete ion channels, with anionic selectivity, was directly demonstrated by electrophysiological experiments performed on planar lipid bilayers or sugar beet vacuoles. The channels show sub-states and their properties in vacuoles and in planar lipid membranes were remarkably similar.
Syringomycin E (SRE), a lipodepsinonapeptide produced by many Pseudomonas syringae pv. syringae strains, displays a prominent antifungal and haemolytic activity. The former is already exploited for post-harvest biocontrol of fruit and appears interesting in the perspective of medical applications; the latter hampers the use of this compound as a systemic drug. The ability to interact with biological membranes and form pores is at the basis of its biological activity. To gain insight into the structural features which are important for this process, we produced structural analogues of the metabolite and evaluated their activity on red blood cells and on artificial membranes of different compositions. The substitution of chlorine with hydrogen in the G terminal amino acid caused a marked decrease in the pore-forming activity, in accordance with the previously observed trend in the antifungal activity assay. The cooperativity of the process is not affected, but the activity of the deschloro-SRE analogue (SREH) at difference from SRE, is not influenced by the presence of sterols in the artificial lipid bilayers. The residual activity of SREH is abolished when the lactone ring is hydrolysed. Thus, both the presence of chlorine in the C-terminal residue and the integrity of the macrocycle appear to be important for the pore-forming activity of SRE.
Control of Pseudomonas syringae pathovars is similar to other phytopathogenic bacteria. Primary control protocols include quarantine, chemical control, host plant resistance, and seed certification. Recently, non protein amino acids such as beta-aminobutyric acid and chemical activators including 2, 6-dichloroisonicotinic acid (INA) and benzo (1,2,3) thiadiazole-7-carbothoioic acid-S-methyl ester (BTH) add an additional facet for control. These chemicals have no or limited effect on the causal agent but invoke plant defence responses such as systemic acquired resistance (SAR).