Bioengineering of nisin to enhance functionality against dairy pathogens

The bacteriocin class of antimicrobial peptides have emerged as a viable alternative to at least partially fill the void created by the end of the golden age of antibiotic discovery. Along with this potential use in a clinical setting, bacteriocins also play an important role as bio-preservatives in the food industry. This thesis focuses on a specific bacteriocin group, the lantibiotics (Lanthionine-containing antibiotics). Their numerous methods of appliance in a food setting and how their gene-encoded nature can be modified to improve on overall bioactivity and functionality are explored here. The use of a lantibiotic (lacticin 3147) producing starter culture to control the Crohn’s disease-linked pathogen Mycobacterium paratuberculosis was assessed in a raw milk cheese. Although lacticin 3147 production did not effectively control the pathogen, the study provided an impetus to employ a variety of PCR-based mutagenesis techniques with a view to the creation of enhanced lantibiotic derivatives. Through the use of these techniques, a number of enhanced derivatives were generated from the ‘hinge’ region of the nisin peptide. Furthermore, a derivative in which the three hinge amino acids were replaced with three alanines represents the first enhanced derivative of nisin to have been designed through a rational process. This derivative also formed the backbone for the creation of an active, trypsin resistant, variant. Through the employment of further mutagenesis methods a derivative was created with potential use as an oral anti-bacterial in the future. Finally a number of lead nisin derivatives were investigated to assess their anti- Streptococcus agalactiae ability, a mastitis associated pathogen. Also a system was developed to facilitate the large scale production of these candidates, or other nisin derivatives, from dairy substrates.

Saothair Oideachais an Ghúim 1926-46

Ceann de phrionsabail bhunaidh An Ghúim téacsleabhair agus leabhair ghinearálta a sholáthar do dhaltaí scoile is do lucht léitheoireachta na Gaeilge. Ábhair a bhaineann le curaclam na scoile, cuir i gcás, eolaíocht is tíos, oideachas, saoránaíocht, spórt, na teangacha Clasaiceacha, tíreolaíocht, taisteal agus an nádúr, creideamh is stair, a roghnaítear don taighde seo. Tugtar Aguisín (921 lch) le bheith ina threoir do phríomh-bhunachar sonraí na dochtúireachta seo (an chiall ghinearálta mar bhailiúchán eolais atá i gceist le “bunachar” sa tráchtas seo in ionad brí theicniúil ar leith). Trí phríomhchuid atá sa staidéar: “buneolas”, “anailís” is “toradh”. Sa “Bhuneolas”, tugtar cuntas beathaisnéiseach ar na bunúdair, soláthraítear achoimre ar na foilseacháin faoi staidéar, mar aon le faisnéis bhibleagrafaíochta i dtaobh na n- aistritheoirí, agus eolas faoi na comhlachtaí foilsitheoireachta a bhí páirteach sna tograí. Pléann “Anailís” brainsí de chuid an státchórais mar an Roinn Oideachais agus an Roinn Airgeadais i gcúrsaí maoinithe, nó gníomhairí lasmuigh de, cosúil le lucht deartha is clóchuradóireachta; moladh is coimisiúnú na saothar; sonraí cóipchirt na bhfoilseachán; roghnú, monatóireacht is díolaíocht na n-aistritheoirí, mar aon le breithniú inmheánach is seachtrach. Sa chuid dheireanach, féachtar le “Toradh” na hiarrachta a mheas, ag tagairt den líon cóipeanna de na leabhair a díoladh. Faightear eolas ar fhiosrú léitheoirí; praghas na leabhar; a ndíolachán is a n- athchló. Tugtar léirmheasanna a scríobhadh ar na haistriúcháin Ghaeilge agus na cúiseanna nár tháinig tograí ar leith chun críche. Is é aidhm na hoibre thar aon ní eile gné lárnach chasta d’eisint An Ghúim atá ligthe i ndíchuimhne a thabhairt ar ais chugainn go beo beathaíoch faoi mar a bhí lena ré saoil féin.