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Infectious diseases have been a problem for humans since the beginning of human existence. The “golden age” of antibiotics started at the end of the 1920s, with the discovery of penicillin by Sir Alexander Fleming. This was followed by the discovery of several life-saving antibiotics. The number of new marketed antibiotics has declined, and most pharmaceutical companies are no longer working in antibiotic development. This in itself would be unproblematic, had it not been for the rapid ability of bacteria to become resistant towards previously debilitating agents. The need for new antibiotics is therefore eminent. Natural products have been important contributors for antibiotic drug discovery and development. Microorganisms have been a particularly proliferative source of antibiotics, providing us with among others the penicillins, aminoglycosides, tetracyclines and polymyxins. Most naturally derived pharmaceuticals, including antibiotics, originate from terrestrial organisms. This is mainly because the terrestrial environment historically has been easier to access compared to the marine environment below the intertidal zone. The marine environment is highly diverse, and there is still a huge biodiversity that is yet to be explored. In this project, Arctic and sub-Arctic marine bacteria and fungi were cultivated and studied for their production of natural products. The cultures were extracted and fractionated, and the fractions were tested for bioactivity, mainly focusing on antibacterial activity. Using bioactivity-guided isolation, compounds were isolated and structurally characterized. Finally, the bioactivity of the isolated compounds was broadly evaluated. In paper I, a known siderophore, serratiochelin A, was isolated from a co-culture of two bacteria, Serratia sp. and Shewanella sp. The compound was not detected in axenic cultures, indicating that cocultivation triggered production. The acid-catalyzed degradation of serratiochelin A into serratiochelin C was also observed. Serratiochelin A had weak activity against Staphylococcus aureus, melanoma cells and non-malignant lung fibroblasts. No activity was observed for the degradation product serratiochelin C, indicating that the oxazoline moiety in the original compound is essential for the bioactivity. In paper II, a marine bacterium Lacinutrix sp. was cultivated and studied for its ability to produce bioactive natural products. Through bioactivity-guided isolation, two new lyso-ornithine lipids were isolated, and their structures elucidated, showing that they only differed by the length of the hydrocarbon tail. Analysis by UHPLC-HR-MS indicate that the purified solutions are mixtures of isomers, but these were not possible to separate by preparative HPLC-MS. The compounds were evaluated for antibacterial activity and antiproliferative activity against human cells. Compound 1 displayed weak activity against Streptococcus agalactiae, while compound 2 had weak activity against melanoma cells. In paper III, a new dimeric naphthopyrone substituted with a sulphate group was isolated in high yields from cultures of an obligate marine fungus in the family Lulworthiaceae. The compound was tested against an extended panel of clinical bacterial isolates and showed potent antibacterial activity against several clinical methicillin-resistant Staphylococcus aureus isolates, with MICs down to 1.56 μg/mL. Acid-catalyzed degradation was also observed. The compound also displayed moderate activities against three human cell lines: melanoma, hepatocellular carcinoma, and non-malignant lung fibroblast. In paper IV, a new chlovalicin variant, chlovalicin B, was isolated from cultures of the obligate marine fungus Digitatispora marina. The fungus has previously been studied for its distribution in the marine environment but has not been extensively studied for its biosynthetic potential. The compound was isolated in low yields, and the structure was elucidated by NMR and HRMS experiments. The compound was assessed for a range of bioactivities and had weak antiproliferative activity against human melanoma cells.

The number of compounds being isolated from the marine environment is increasing, and there is a great potential for discovering new marine derived drug candidates. Improved collection techniques has strengthened bioprospecting on a wider diversity of marine microorganisms. The focus on microorganisms has led to the realisation that many of the natural products originally isolated from macroorganisms, are metabolic products produced by their associated microorganisms. This, and the fact that most marketed antimicrobial drugs originate from microorganisms, motivated the work conducted as part of this thesis. In this study, two Arctic marine bacteria of the genus Leifsonia and Polaribacter were studied. The “One Strain-Many Compounds” (OSMAC) approach was utilised when cultivating the bacteria, in an attempt to trigger the bacteria into activating different metabolic pathways and producing compounds with interesting chemistry and bioactivity. Seven different cultivation treatments were used, varying different parameters e.g. media composition and temperature. The secondary metabolites secreted by the cultivated bacteria were harvested, extracted and prefractionated. The fractions were screened for antibacterial activity, inhibition of biofilm formation and anticancer activity. The bioactivity screening resulted in eight active fractions. Dereplication of the active fractions gave several candidates that could be responsible for the observed bioactivity. The results from this thesis give a valuable starting point for further research on cultivation of Arctic marine bacteria, with the purpose of producing bioactive secondary metabolites.

Master's thesis in Change management Det er ikke lenger diskusjon eller tvil om at røyking er helseskadelig, og ulike former for tobakksforebyggende tiltak er nå veldig i tiden. Forskning viser at røyking er i en utløpsfase her til lands, både på grunn av røykingens endrede symbolinnhold og endringer i tobakkslovgivningen. Den 1. oktober 2015 ble Stavanger kommune en røykfri arbeidsplass. Et røykeforbud ble innført for alle ansatte. Forbudet ble i tillegg utvidet til å gjelde all tobakk, både røyk, snus og e-sigaretter, for ansatte i barnehager og skoler. Forbudet kom som en følge av endringer i Tobakkskadeloven, men også på grunn av flere års internt arbeid med problematikken i den kommunale ledelsen, og i ulike Arbeidsmiljøutvalg. Denne oppgaven er en kvalitativ analyse av innføringen av røykfri arbeidstid for ansatte i Stavanger kommune, hvor gruppeintervju er benyttet som metodisk tilnærming. Ved å intervjue fem ulike kommunale virksomheter ønsker oppgaven å drøfte innføringen og implementeringen av røykfri arbeidstid i kommunen, fra de ansattes ståsted. Mer konkret fokuseres det på hvordan de de ansatte har opplevd røyke- og tobakksforbudet. Følgende problemstilling er formulert: «Hvordan opplever de ansatte innføringen og implementeringen av røykfri arbeidstid i Stavanger kommune? Hvilke likheter og forskjeller er det mellom virksomheter i ulike avdelinger og fagområder?» Innsamlet data blir i oppgaven sett i sammenheng med teori om kontekstualisering – da spesielt relatert til ulike kontekster i virksomhetene – og det instrumentelle, det institusjonelle og det ny-institusjonelle perspektivet. De tre organisatoriske perspektivene blir fortolket komplementært. Denne komplementære tilnærmingen vektlegger at de ulike perspektivene forklarer forskjellige deler av innsamlet data. De formelle prosessene relatert til forbudet forklares hovedsakelig ut ifra det instrumentelle perspektivet. Videre forstås informantenes – og som en forlengelse de ansattes – opplevelse av forbudet ut ifra det institusjonelle perspektivet. Ny-institusjonelle trekk relateres hovedsakelig til de informantene og gruppene som vektla at forbudet kan sees som en naturlig del av samfunnsutviklingen. Hovedfunnet i oppgaven er at implementeringen av røykfri arbeidstid tilsynelatende har vært vellykket. Data viser imidlertid at den vellykkede implementeringen ikke skyldes formelle handlinger eller tiltak fra kommunens side, men heller allerede eksisterende normer og verdier hos de ansatte. Dette relateres både til en generelt lav røykeandel blant de ansatte og en bred forståelse for slike tiltak som en naturlig del av samfunnsutviklingen. Data avdekker samtidig at de ansatte har opplevd forbudet noe ulikt. Dette knyttes både til ulike fagområder og konteksten i de enkelte virksomhetene. Hvis ingen av de ansatte røyker, vil ikke forbudet føre til en annerledes situasjon. En slik kontekst vil derfor gjøre implementeringsprosessen lettere enn for eksempel en kontekst med flere røykere. Videre ble mangelen på sanksjoner fremhevet som en årsak til at forbudet muligens ikke ville bli etterlevd av alle ansatte. Det at de folkevalgte vedtok at forbudet ikke skulle gjelde for dem var et annet aspekt flere informanter fremhevet som negativt. Når den øverste ledelsen «slipper» det samme forbudet som de pålegger sine ansatte, vil det være naturlig med reaksjoner. Oppgaven konkluderer med at implementering av de formelle prosessene i tilknytning til forbudet har vært vellykket, men at de ansatte i de forskjellige virksomhetene har opplevd forbudet ulikt. Dette kan både knyttes til forskjellige fagområder, ulik kontekst relatert til røykeandel, mangel på sanksjoner, negative holdninger tilknyttet de folkevalgtes fritak og ulike generelle holdninger til tobakksrestriksjoner. Disse oppfatningene kan ikke forklares med et organisatoriske perspektiv alene. Dermed blir den komplementære tilnærmingen som er valgt i denne oppgaven avgjørende, da perspektivene forklarer forskjellige deler av data.