Activation of mammalian stress responsive pathways by plant secondary metabolites may contribute to the protection against certain chronic diseases afforded by fruit and vegetable consumption. This work focuses on the identification of plant compounds that activate the stress-responsive enzyme quinone reductase (QR) by stabilizing the transcription factor NF-E2 related factor-2 (Nrf2). Screening methanolic extracts of plants from Western Canada for QR induction in a mouse hepatoma cell line (Hepa-1c1c7) led to the identification of twenty-one extracts capable of doubling the activity of QR. Bioassay-guided fractionation of six extracts led to the identification of novel classes of compounds with QR-inducing activity including fatty-acid derived polyacetylenes, phthalides, and cannabinoids. Studies using low molecular weight thiols and the recombinantly expressed protein Keap1, the principal negative regulator of Nrf2, supported a mechanism of QR activation involving covalent modification of Keap1 cysteines for the polyacetylenes and phthalides. Analysis of transcriptional changes in response to treatment with a panel of QR-inducing compounds provided strong support for Nrf2 activation by the polyacetylene (3S,8S)-falcarindiol and the isothiocyanate (R)-sulforaphane and weaker support for the compounds (3R,8S)-falcarindiol, 6-isovaleryl-umbelliferone (6-IVU) and (Z)-ligustilide. Additionally, transcript level analyses supported a role for the aryl-hydrocarbon receptor in QR-activation by (3R,8S)-falcarindiol, (Z)-ligustilide, (R)-sulforaphane, 6-IVU and cannabidiol and suggested that treatment with polyacetylenes with a (3R)-configuration, (Z)-ligustilide and 6-IVU causes substantial changes in the expression of genes associated with lipid homeostasis and energy metabolism. As a whole, this work provides evidence that compounds that activate QR (and Nrf2) are widely distributed in the Canadian flora. However, of these QR activators, few are active at concentrations that are expected to be achieved through dietary consumption. Nevertheless, the most exceptional compounds isolated in this work, the compounds (3S,8S)-falcarindiol and epoxyfalcarindiol are highly potent and appear to be or are expected to be specific for activating Nrf2 and thus warrant attention with respect to dietary implications and as drug candidate leads.

The theoretical part of this doctoral thesis provides a comprehensive overview on the topic of preparation and subsequent utilization of magnetic derivatives of biological materials for xenobiotic separation from water. Main attention is paid to magnetic modification of waste materials and by-products originating from agricultural and food industry, which represent widely available and low-cost materials, and also to magnetic modification of microbial cells. In addition to the description of magnetic particle preparation and individual developed techniques of magnetic modification, a brief characterization of selected pollutants and a detailed table overview on utilization of magnetically responsive biomaterials for biosorption of organic dyes, heavy metals, pharmaceutical and personal care products together with ubiquitous industrial endocrine disruptors and also of crude oil derivatives is presented. Experimental part of this thesis is focused on the preparation and optimization of new types of magnetic materials. Emphasis is placed on the employment of simple, fast and simultaneously low-cost magnetic modification techniques (e.g., postmagnetization using microwave-synthesized magnetic iron oxides or one-step modification by magnetic fluids). Selected plant materials (barley and rye straw) were chemically modified to significantly (up to five-times) increase the maximum adsorption capacities for tested dyes. All prepared biomaterials exhibited a great magnetic response and simultaneously relatively high adsorption capacity for selected xenobiotics under experimental conditions used. Factors substantially affecting adsorption process, such as pH, initial concentration, incubation time or temperature were also studied. Adsorption equilibrium data were assessed using Langmuir, Freundlich or Sips isotherm models. Experimental data from time dependence study were analyzed by chosen kinetic models, namely the pseudo-first-order and pseudo-second-order ones and by intraparticle diffusion model. Thermodynamic parameters (Gibbs free energy, enthalpy and entropy) describing the nature of adsorption were also included in study.

Les protéines régulatrices de la transcription de type LysR (LTTR) appartient à la plus grande famille de facteur de transcription chez les procaryotes. Malgré l'importance de cette famille, les informations structurelles sur les protéines pleine-longueur sont très limitées car elles sont souvent insolubles et très difficiles à cristalliser. Les quelques structures existantes, couplés à d'autres analyses biophysiques ont pu montrer que ces protéines s'associent principalement sous forme d'homotétramère comprenant un dimère de dimères. Les dimères s'associent par un large domaine C-terminal dans une position " tête-bêche " et sont reliés en " tête-à-tête " par leurs domaines N-terminal et sont activées par la liaison de molécules inductrices. Le domaine dimèrique C-terminal qui contient la poche de liaison inductrice (Inducer Binding Cavity : IBC) est appelé domaine de liaison inductrice (Inducer Binding Domain : IBD), tandis que les dimères N-terminaux se lient chacun à une région de l'ADN par un motif hélice-tour-hélice ‘winged' (wHTH). Contrairement à d'autres facteurs de transcription, les protéines LTTR ne régulent pas l'expression par association/dissociation avec l'ADN. Ils se lient à l'ADN dans leur état actif et inactif. Le consensus actuel est qu'elles régulent l'expression des gènes par d'importants changements conformationnels qui relâchent la liaison avec l'ADN. À ce jour, aucune structure de LTTR pleine longueur homotétramérique dans une conformation active ou inactive n'a été résolu par cristallographie, et leur mécanisme d'action sur le gène reste structurellement non caractérisé.Le travail décrit dans cette thèse a utilisé DntR de la famille des LTTR. La première structure cristalline de l'apo-DntRis est présentée ici, ainsi que la structure du mutant H169TDntR, qui présente une activité en l'absence d'inducteur. L'analyse par fluorimétrie de différentiel thermique (TSA) montre que la température de dénaturation du mutant H169TDntR est similaire à DntR IBDs lié à une molécule inductrice. La comparaison de ces deux structures avec celle de DntR lié au salicylate révèle que la protéine dans son état apo adopte une conformation compacte de l'IBC, ce qui empêche la liaison d'une molécule inductrice. Dans l'IBC, les mouvements des résidus H169 et H206 permettent la liaison à l'inducteur. Pour éviter les limitations dues à l'empaquetage du cristal nous avons étudié la structure DntR en solution par diffusion des rayons X aux petits angles (SAXS).L'étude SAXS de DntR révèle que dans son état inactif, la conformation apo adopte un repliement plus compact par rapport à celle de la structure cristalline. Tout en maintenant un noyau compact de C-terminal, le repliement du dimère de wHTH est beaucoup plus fermé que dans la structure cristalline et adopte une conformation qui entrainerait une flexion beaucoup plus importante de l'ADN lié que postulé précédemment. Les études du mutant H169TDntR constitué actif ont confirmé comme l'analyse par TSA l'a suggéré que, la structure de cette protéine est nettement différente en solution que sous forme cristalline.En effet, la structure en solution de H169TDntR est très semblable à la forme ouverte de l'homotétramères observés dans la structure cristalline de TsaR. L'hypothèse de départ était que, lors de l'activation de LTTR, cet homotétramère subirait un changement de conformation d'une forme compact vers une forme ouverte, qui se traduirait par un relâchement de l'ADN lié. Cette hypothèse a été confirmée par des études de diffusion en solution de DntR activée par un inducteur.Le travail présenté dans cette thèse valide l'hypothèse précédemment, que lors de l'activation de DntR, et probablement tous les LTTRs homotétramériques, entraine un changement de conformation d'une forme compacte vers une forme beaucoup plus ouverte et permet l'accès aux régions promotrices par l'ARN polymerase et ainsi initier la transcription. / LysR type transcriptional regulatory (LTTR) proteins are the largest family of transcription factors amongst prokaryotes. In spite of the size of the family, structural information on full-length constructs of these proteins is very limited as they are often insoluble and very difficult to crystallize. From the few existing crystal structures, coupled with other biophysical evidence, it is known that the proteins mainly associate as homotetramers comprising a dimer of dimers. The dimers associate through large C-terminal domains in a “head-to-tail” fashion and are connected “head-to-head” through their N-terminal domains and the resulting homotetramers are activated by the binding of inducer molecules. Each C-terminal domain contain an inducer binding cavity (IBC) and is denoted an inducer binding domain (IBD), while the N-terminal dimers each bind a region of DNA via a winged helix-turn-helix (wHTH) motif.Unlike other transcription factors, LTTR proteins do not regulate expression by associating or disassociating with DNA. They bind to DNA in both their active and inactive states and the current consensus is that they regulate gene expression through large conformational changes that relax the bending of bound DNA. However, to this date, no crystal structures of a full length homotetrameric LTTR in both an active and inactive conformation exists, and thus their mechanism of transcriptional regulation remains structurally uncharacterized.The work described in this thesis has used the LTTR DntR as a model protein to futher structurally characterizes the activation mechanism of LTTR proteins. The first crystal structure of apo-DntR is presented as is the crystal structure of H169TDntR, a mutant which shows activity in the absence of an inducer molecule. Thermofluor assays performed on this mutant, show that it has a melting temperature similar to that of inducer bound DntR. Comparison of these crystal structures with the crystal structure of salicylate-bound DntR reveals that the protein in its apo-state adopts a compact IBC, which precludes the binding of an inducer molecule. Despite the evidence of thermofluor assays, the crystal structure of H169TDntR is very similar to that of apo-DntR suggesting that crystal packing effects impose strong limitations on the use of crystallography to elucidate the active and inactive conformations of DntR. Small Angle X-ray Scattering (SAXS) was thus used to study the structure of DntR in solution.SAXS study reveals that in solution DntR in its inactive apo-state is found in a slightly different conformation compared to that seen in its crystal structure. While maintaining a compact tetrameric C-terminal core the DNA binding wHTH dimers pack much closer to this than seen in the crystal structure and adopt a conformation that would result in much higher bending of bound DNA than previously postulated.SAXS studies of the constitutively active H169TDntR mutant confirm, as thermofluor assays had suggested, that in solution the structure of this protein is markedly different from its crystal structure. Indeed the solution structure of H169TDntR appears very like that of open-form homotetramers seen in the crystal structure of TsaR. This same effect was observed in solution scattering studies of inducer bound-and thus activated, DntR.The work presented in this thesis thus appears to confirm, as previously hypothesized, that upon activation DntR, and presumably all homotetrameric LTTRs, undergo a conformational change from a compact, to a much more open form that allows the relaxation of the bound DNA promoter region, exposing it to solvent and allows RNA polymerase access and thus initiate transcription.

Le foie est le principal organe impliqué dans la biotransformation des xénobiotiques. Les cytochromes P450 (CYP) en sont des enzymes dés. Parmi elles, leCYP4A est impliqué dans rhydroxylatlon des acides gras et la biotransformation de médicaments, tels que le bézafibrate (BE2A), un hypolipémiant utilisé enthérapeutique humaine. Cette molécule a été montrée hépatocarcinogène chez les rongeurs mais cet effet n'a pas été rapporté chez l'Homme. H est doncimportant de connaître les mécanismes d'action impliqués dans les effets du BEZA chez l'Homme. Dans une première étude, nous avons étudié l'expression duCYP4A au niveau ARNm et apoprotéine ainsi qu'au niveau de son activité dans des cultures primaires d'népatocytes de rat et d'Homme traitées ou non par duBEZA et de la N-acétylcystéine, molécule précurseur du glutathion. Nous avons mis en évidence d'importantes différences Interespèces et l'influence del'environnement redox des cellules en termes de réponse aux Inducteurs. L'implication des récepteurs nucléaires PPARa, PXR et CAR et des CYP4A/3A/2B aensuite été évaluée pour expliquer les différences inter-espèces observées. D'autre part, nous avons montré pour la première fois que le BEZA diminuel'expression de l'ARNm de OATP2 chez le rat et la biodisponibilité des statines en utilisant un système de biochromatographie original. Enfin, nous avonsmontré que le BEZA, en fonction de l'environnement redox de la cellule, régule des protéines impliquées dans le métabolisme des acides gras et lipides, ainsique des biomarqueurs d'hépatocarcinogenèse chez l'Homme, ce qui pose réellement la question du bien-fondé de l'utilisation de cette molécule enthérapeutique / The liver is the main organ involved in biotransformation of xenobkrtics invotving the cytochrome P450 (CYP). Among thèse enzymes, the CYP4A participate in the <o-hydroxylat!on of fatty acids and the met a bolis m of drugs such as be zafibrate (Beza), a lipld-lo wering molécule used In human therapy. It has been shown hepatocarcinogen In rodent; but no effect was reported in humans. It is thus important to understand thé mechanisms of action of Beza in humans. In a first study, we Investigated the expression of CYP4A at the mRNA, apoprotein and activity leveis In primary cultures of rat and human hepatocytes treated or not wlth Beza and/or N- acetylcysteine, a glutathtone precursor. We hâve highlighted Important différences between spedes and the Influence of ce» redox envlronment in terms of response to inducers. The involvement of nudear receptors PPARa, PXR and CAR and of CYP4A/3A/2B was then evaluated to explain the différences observed between species. On the other hand, we showed for the flrst time that Beza decreases the expression of rat OATP2 mRNA and the bioavailability of statins by uslng an original biochromatography System. Flnally, we showed that Beza, dependlng on the cellular redox envlronment modulâtes proteins involved In the metabolism of fatty acids and liplds, and also some biomarkers of hepatocarcinogenesis In humans, which raises the reai question a bout the appropr iateness of using t h is drug in human therapy.

Abstract The hepatic inducible Cytochrome P450s (CYPs) generally prime xenobiotics for elimination. Murine CYP2A5 and human CYP2A6 share similar xenobiotic substrates and some regulatory features. Recently, they were shown to oxidize bilirubin, a byproduct of heme catabolism and a dose-dependent anti- or pro-oxidant, to biliverdin. In this study, the putative role of the redox-sensitive, cytoprotective transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the regulation of hepatic Cyp2a5 expression and induction under diverse hepatotoxic conditions and altered heme homeostasis was characterized. The coordination of Cyp2a5 and the Nrf2 target gene Heme oxygenase-1 (Hmox1), which determines bilirubin formation from heme, responses to heavy metals and modulators of heme homeostasis, was studied in cultured wildtype and Nrf2(-/-) mouse primary hepatocytes. Nrf2 was essential for the basal hepatic expression of CYP2A5 in the endoplasmic reticulum (ER) and mitochondria, as well as for its induction by cadmium, lead, methyl mercury and phenethyl isothiocyanate. A functional Nrf2 binding antioxidant response element (ARE) about -2.4 kilobases upstream of the Cyp2a5 transcriptional start site was identified. In contrast to Hmox1, a target of BTB and CNC homology 1 (Bach)-mediated repression via AREs, the regulation of Cyp2a5 did not clearly involve Bach1. Excessive heme induced mainly ER-localized CYP2A5 via Nrf2, which was limited by the Nrf2-independent HMOX1 induction. In heme synthesis blockades, CYP2A5 was enhanced via Nrf2 and additional factors, such as the peroxisome proliferator-activated receptor &#947; coactivator-1&#945; (PGC-1&#945;). The typical CYP2A5 inducers phenobarbital, dibutyryl-cyclic adenosine monophosphate (db-cAMP) and PGC-1&#945; enhance heme synthesis; CYP2A5 was induced via Nrf2 in acute but not chronic phenobarbital exposure without a clear connection to heme, while the responses to db-cAMP and PGC-1&#945; were sensitized in the absence of Nrf2. This suggests novel crosstalk between Nrf2 and PGC-1&#945;. In this study, Cyp2a5 was identified as a sensitive indicator of hepatic Nrf2 pathway activation that could be used, e.g. for in vitro screening of drug candidate hepatotoxicity. The similar subcellular localization and coordination of CYP2A5 and HMOX1 expression in altered heme metabolism support the postulated role for CYP2A5 in bilirubin homeostasis. / Tiivistelmä Vierasaineet stimuloivat maksan Sytokromi P450 (CYP)-entsyymejä, mikä yleensä lisää niiden eliminaatiota. Hiiren CYP2A5 ja ihmisen CYP2A6 ovat lähisukua katalyyttisten ja osin säätelyllisten yhteneväisyyksiensä puolesta. Vastikään niiden osoitettiin katalysoivan hemin hajoamistuotteen, bilirubiinin hapettumista biliverdiiniksi, mikä saattaisi säädellä sen annosriippuvaisia vaikutuksia antioksidanttina ja oksidanttina. Työssä tutkittiin solustressiä aistivan, suojaavan transkriptiotekijän Nrf2 osuutta Cyp2a5-geenin aktivaatiossa maksatoksisissa olosuhteissa ja hemimetabolian muutoksissa. Cyp2a5:n ja bilirubiinin tuotosta vastaavan, Nrf2-säädellyn Hemioksigenaasi-1 (Hmox1):n vasteita verrattiin viljellyissä villityypin ja poistogeenisen Nrf2(-/-) hiiren primaarimaksasoluissa. Tulokset osoittavat, että Nrf2 ylläpitää CYP2A5:n ilmentymistä endoplasmisella kalvostolla (ER) ja mitokondrioissa sekä välittää sen stimulaation altisteilla kadmium, lyijy, metyylielohopea ja fenetyyli-isotiosyanaatti. Toimiva Nrf2-vasteinen antioksidanttivaste-elementti (ARE) tunnistettiin n. -2,4 kiloemäsparia Cyp2a5-geenin luennan aloituskohdasta ylävirtaan. BTB ja CNC homologia 1 (Bach1)-tekijä, joka on tärkeä Hmox1-säätelijä ja ARE-välitteinen transkription estäjä, ei selkeästi osallistu Cyp2a5:n säätelyyn. Hemin ylimäärä stimuloi CYP2A5:n määrää ER-kalvostolla, Nrf2-riippumattomasti stimuloituvan HMOX1 rajoittaessa Nrf2-reitin aktivaatiota. Hemisynteesin estyessä Nrf2 aktivoi Cyp2a5-geeniä muiden mekanismien kuten peroksisomiproliferaattori-aktivoituva reseptori gamman koaktivaattori-1&#945; (PGC-1&#945;) kanssa. Fenobarbitaali (PB), dibutyryyli-syklinen adenosiinimonofosfaatti (db-cAMP) ja PGC-1&#945; lisäävät tunnetusti hemisynteesiä. Nrf2 havaittiin Cyp2a5:n aktivaatiolle välttämättömäksi akuutissa mutta ei kroonisessa PB-altistuksessa ilman selkeästi havaittua hemin osuutta. Cyp2a5-geenin db-cAMP- ja PGC-1&#945;-vasteinen stimulaatio voimistui merkittävästi toimivan Nrf2-reitin puuttuessa, mikä osoittaa vuoropuhelua Nrf2 ja PGC-1&#945; välillä. Väitöskirjatyössä Cyp2a5 tunnistettiin herkäksi Nrf2-reitin aktivaation maksamarkkeriksi, jota voitaisiin hyödyntää esim. lääkeainekandidaattien maksatoksisuuden seulonnassa soluviljelyssä. CYP2A5:n ja HMOX1:n solunsisäinen kohdentuminen ja ekspressio koordinoituvat hemimetabolian muutoksissa, mikä tukee teoriaa CYP2A5:n roolista bilirubiinin metaboliassa maksassa.

La stéatose est la pathologie hépatique la plus répandue dans le monde, touchant environ 25 % de la population générale et jusqu’à 80 % des personnes en surpoids ou obèses. Cette maladie se traduisant par l’enrichissement des hépatocytes en triglycérides, est considérée comme bénigne. Cependant, environ 20 % des personnes atteintes de stéatose développent une stéatohépatite, pathologie caractérisée par une mort cellulaire et une inflammation et représentant un stade favorable au développement du carcinome hépatocellulaire. Les causes et mécanismes impliqués dans la progression de la stéatose vers la stéatohépatite sont encore à préciser. L’obésité, l’exposition aux contaminants environnementaux et la consommation d’alcool sont trois facteurs participant au développement des pathologies hépatiques. Pourtant, l’effet de l’interaction entre ces différents facteurs sur les pathologies hépatiques n’est pas connu. Dans ce contexte, cette thèse a eu pour objectif d’étudier l’impact d’une co-exposition au benzo[a]pyrène (B[a]P), un contaminant carcinogène environnemental, et à l’éthanol, utilisé à de faibles doses, sur les cellules hépatiques WIF-B9, présentant une stéatose préalable. Les résultats obtenus ont permis de démontrer qu’une telle exposition induit une progression de la stéatose hépatique vers un stade apparenté à une stéatohépatite, marquée par une augmentation de la mort cellulaire et de l’inflammation. Nous avons mis en évidence que la mort cellulaire résulterait de l’activation de p53 et d’une peroxydation lipidique. Une activation du récepteur aux hydrocarbures aromatiques et une production de monoxyde d’azote sont à l’origine de ces évènements via une modification du métabolisme de l’éthanol et du B[a]P conduisant à des dommages à l’ADN dépendants de la formation d’anion peroxynitrite. / Steatosis is the most common form of liver disease in the world, affecting around 25 % of the general population and up to 80 % of obese people. The disease is defined by the accumulation of triglycerides in hepatocytes and is generally considered as a benign condition. However, around 20 % of people with steatosis develop steatohepatitis, a disease characterized by cell death and inflammation, a condition that favors the development of hepatocellular carcinoma. The causes and mechanisms involved in the progression from steatosis to steatohepatitis are yet not fully understood. Obesity, exposure to environmental contaminants and alcohol consumption are three major factors contributing to the development of liver diseases. However, is still not yet clear what is the effect of the interaction between these different factors on liver diseases. In this context, the aim of this study was to evaluate the impact of a co-exposure to benzo[a]pyrene (B[a]P), an environmental carcinogenic contaminant, and ethanol, used at low doses, in WIF-B9 hepatic cell line, with a prior steatosis . The results demonstrate that this type of co-exposition induces a progression of hepatic steatosis to a steatohepatitis-like stage, marked by an increased cell death and an inflammation. We have shown that in this condition, cell death results from the activation of p53 and lipid peroxidation. Activation of the aromatic hydrocarbon receptor and production of nitric oxide are the origin of these events by a modification of both ethanol and B[a]P metabolism leading to peroxynitrite-dependent DNA damage.

Clarireedia spp. (formerly Sclerotinia homoeocarpaF.T. Bennett) is the causal agent dollar spot, the most economically important turfgrass disease impacting golf courses in North America. The most effective strategy for dollar spot control is repeated application of multiple classes of fungicides. However, reliance on chemical application has led to resistance to four classes of fungicides as well as multidrug resistance (MDR). Fungi are known to detoxify xenobiotics, like fungicides, through transcriptional regulation of three detoxification phases: modification, conjugation and secretion. Little is known, however, of the protein-protein interactions that facilitate these pathways. Following next-generation RNA sequencing of Clarireedia spp., a fungus-specific transcription factor, XDR1, was determined to play a role in constitutive and induced overexpression of phases I and III genes of xenobiotic detoxification. Further, a novel activation domain (AD) on XDR1 that does not directly bind with xenobiotics was confirmed to be highly conserved among fungal species. Therefore, we hypothesize that XDR1 must be activated by interacting with other binding partners at this AD in order to regulate downstream xenobiotic detoxification pathways. The main objective of this study is to identify additional proteins/ co-repressors that activate XDR1 in order to gain a better understanding of how transcriptional regulation of xenobiotic detoxification pathways leads to MDR. In order to test the hypothesis, fungicide sensitive strain (HRS10) and fungicide resistant strain (HRI11) were transformed and tagged with xdr1/XDR1 and the 3xFLAG tag. As a result, four fungal transformants were generated and those are HRS10-XDR1-3xFLAG, HRS10-xdr1- 3xFLAG, HRI11-XDR1-3xFLAG, and HRI11-xdr1-3xFLAG. The total protein extractions (whole cell lysates) were subjected to co-immunoprecipitation and the samples were analyzed using LC-MS/MS. According to the set of results, more than 50 proteins were detected with HRS10-XDR1-3xFLAG with and most of these binding partners having functions related to post translational modification, protein turnover, intracellular trafficking, secretion and vascular transport. Going forward, information gained from this experiment could be used to explore how XDR1 interacts with its binding partners to facilitate the transcription of drug metabolizing genes responsible for multidrug resistance. This information could also help identify additional fungicide metabolism pathways in filamentous fungi.

No description available.

Egentligen hade jag aldrig tänkt arbeta med något så till synes opoetiskt som gifter, girighet och genetik i mina konstnärliga och musikaliska verk – mina tidigare verk är mer tvetydiga till sin natur. Men som någon sagt; alla intryck måste få ett uttryck. I synnerhet då det är fråga om livsomvälvande upplevelser som delas av en globalt växande grupp men samtidigt sällan kan uttryckas i brist på allmän kännedom. För mig och denna grupp jag upptäckt handlar det om hur överexponering för (bio)toxiner samverkat med genetiska variationer och gradvis förstört våra immunförsvar samt gett upphov till sk. environmental illness och en rad sammanlänkade följdtillstånd. Mina verk från den här tiden förmedlar kanske ändå klanger och spår av detta på ett poetiskt, universellt och mångbottnat sätt, medan uppsatsen är mera konkret – syftet är att ge ett ytskrap av minoritetserfarenheter med kollektiva och politiska ansatser, analysera deras avspeglingar i mina musikaliska verk och därefter utforska om och hur dessa avtryck upplevs av andra. Endel konstverk berörs i denna text men huvudsakligt fokus ligger, liksom under utbildningen, på mitt musikaliska uttryck. Slutligen tangerar jag nya verk, till vilka jag hoppas bära med mig insikter om musiken som konstnärligt, kommunikativt medium.

No description available.