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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

O poder vai dançar de Tim Robbins: história, avanços e limites / Cradle will rock by Tim Robbins: history, advances and limits

Branco, Neyde Figueira 19 April 2011 (has links)
Esta pesquisa se utiliza do filme O poder vai dançar (Cradle will rock, 1999), dirigido por Tim Robbins, para entender a História, os avanços e limites de dois momentos históricos: a década de 1930 e a de 1990 nos Estados Unidos. Definido como uma história predominantemente verdadeira, o filme apresenta personagens e fatos reais e fictícios, que se alternam e se relacionam. Ele é composto por uma série de narrativas, aparentemente fragmentadas e desconexas, mas cujas relações são construídas em todo o seu decorrer. De modo geral, podemos dizer que o filme retrata a década de 1930, momento de potencial revolucionário na História dos Estados Unidos, uma vez que a crise econômica potencializou e tornou visíveis os problemas decorrentes do sistema capitalista. Em seu intento, o diretor se aproxima da concepção benjaminiana de História, à medida que, mais do que simplesmente reproduzir a narrativa desse período, opta por se apropriar de um momento explosivo do passado, carregado de elementos em comum com o presente, e utilizar a citação do passado como fonte de inspiração no combate presente. Ou seja, parte desse passado para na verdade dizer algo sobre a realidade em que está inserido, da década de 1990. Assim, ao pensar sobre esses contextos históricos, nos possibilita refletir sobre suas características, motivações e conseqüências. Para tanto, Tim Robbins se utiliza de elementos do teatro épico, e não apenas retrata os elementos históricos do período, mas busca principalmente provocar uma reflexão por parte da audiência. E tal reflexão vai além do entendimento da história, avança sobre questões como o reconhecimento pelo artista de sua condição de proletário da cultura e sobre o limite que se coloca entre fazer arte paga por empresas e a prostituição, entre outras. / This research makes use of the movie Cradle will rock (1999), directed by Tim Robbins, to understand the History, progresses and limits of two historical periods: the decades of 1930 and 1990 in the United States. Defined as a (mostly) true story, the movie presents real and fictional characters and facts, which are alternated and connected to each other. It has a series of narratives, aparently fragmented. However, its connections are built in the course of the movie. In general, we can say that the film portrays the decade of 1930, moment of revolutionary potential in the History of the United States, as a result of the economical crisis, that made visible all the problems deriving from the capitalistic system. In his intent, the director approaches the conception Benjamin has of the History, as he chooses to go beyond than only narrate the facts of the period and decides to appropriate of such an explosive moment of the past, replete of elements in common with the present, and use the citation of the past as a source of inspiration in the current battle. That is, uses the past in order to say something about the reality he experiences in the decade of 1990. In this manner, we can consider these historical periods and reflect on its characteristics, motivations and consequences. In order to do that, Tim Robbins makes use of elements of the epic theater, and not only depicts the historical elements of the period but also tries to provoke the audience and make them reflect about the facts and elements he exposes. These reflections surpass the understanding of the History and reaches questions such as the recognition of the artist of his condition of proletarian of the culture and the limit between making art sponsored by companies and the prostitution of the artist, among other.
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42

Contes gothiques, Tim Burton : de Vincent à Miss Peregrine’s Home for Peculiar Children / Gothic tales, Tim Burton : from Vincent to Miss Peregrine’s Home for Peculiar Children

Colombani, Elsa 14 November 2018 (has links)
Le cinéma de Tim Burton se reconnaît par des codes thématiques et des images si aisément identifiables que le nom du cinéaste a donné naissance à l’adjectif « burtonien ». Que signifie au juste ce qualificatif ? Cette thèse se propose de démontrer que si la signature de Tim Burton est reconnaissable entre toutes, c’est qu’elle porte l’héritage des gothiques littéraire et cinématographique. Burton s’en empare pour les transformer, adoptant une double stratégie d’adhésion et d’inversion des tropes du genre. Afin de définir ce gothique burtonien, nous étudions dans un premier temps le croisement entre l’humain et le monstrueux, un questionnement directement hérité du Frankenstein de Mary Shelley et de son adaptation éponyme par James Whale en 1931. Nous analysons ensuite la géographie de l’espace burtonien et sa représentation d’une société cruelle et machinique dont les personnages doivent s’extraire pour survivre. L’art émerge comme un moyen de survie ambivalent qui nous mène à considérer la création artistique du cinéaste lui-même, bâtie comme les grandes œuvres gothiques sur un brouillage des frontières, entre la vie et la mort, le passé et le présent, le rêve et la réalité. / The films of Tim Burton can easily be recognized by their thematic codes and identifiable images so much so that the director’s very name has given birth to the adjective “Burtonian”. But what does it qualify exactly? This dissertation proposes to demonstrate that Burton’s signature is particularly recognizable because it inherits from gothic literature and film. Burton tackles and transforms gothic tropes using a double strategy of adherence and reversal. To define what we call the “Burtonian gothic”, we first study the crossing between the humane and the monstrous, an issue directly inherited from Mary Shelley’s Frankenstein and its film adaptation by James Whale in 1931. We analyze then the geography of the Burtonian landscape and its representation of a cruel and mechanical society from which the characters must escape to survive. Art emerges as an ambivalent means of survival which leads us to consider the artistic creation of the filmmaker himself, built like great gothic works on blurred frontiers, between life and death, past and present, dream and reality.
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43

Jornalismo Rá-Tim-Bum: uma proposta de vínculos entre imprensa, escola e criança

Pereira, Heron Ledon 28 June 2018 (has links)
Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2018-08-13T13:05:39Z No. of bitstreams: 1 Heron Ledon Pereira.pdf: 1875659 bytes, checksum: 264b87da07d9f083a3c33271a0541d18 (MD5) / Made available in DSpace on 2018-08-13T13:05:39Z (GMT). No. of bitstreams: 1 Heron Ledon Pereira.pdf: 1875659 bytes, checksum: 264b87da07d9f083a3c33271a0541d18 (MD5) Previous issue date: 2018-06-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This research investigates Brazilian children's journalism in recent years and proposes a closer relationship between the press, school and children. Therefore, this study reveals how the TV program Castelo Rá-Tim-Bum can serve as an inspiration for this type of journalism in the country. Unveiled from 1994 to 1997, Castelo is one of the leading children's series in the history of Brazilian TV, with high ratings and international recognition of specialists. Produced by TV Cultura, it returned to gain prominence in the cultural scene of the country in 2014, when it completed 20 years of existence, with exhibitions, new plays and materials in the media. This work brings together historical and recent examples of journalism for children – including universities – and the production of children's content on TV, Internet, cinema, radio, music, literature, comics and theater. It also presents summaries of the main children's programs of TV Cultura before and after Castelo. About the series, this dissertation covers details of the characters, paintings and rooms of the enclosure, as well as old products and recent fruits of attraction. The analysis points out elements that can contribute to journalism for children and with them. There are six topics: children's issues; the role of the journalist; investigation and discovery; playfulness; sounds; children want to talk. The understanding of communication is used as link building, according to Baitello Junior. The concept of ecology of communication, according to Romano, bases the reflection on communication practices that involve children. It is understood the field of educommunication from Soares, and the ideas of Leão about hypermedia help sketch an example of how the results are applied / Esta pesquisa investiga o jornalismo infantil brasileiro nos últimos anos e propõe uma maior aproximação entre imprensa, escola e criança. Para isso, observa-se como o programa Castelo Rá-Tim-Bum pode servir de inspiração para esse tipo de jornalismo no país. Exibido ineditamente de 1994 a 1997, o Castelo é uma das principais séries infantis da história da TV brasileira, com altos índices de audiência e reconhecimento internacional de especialistas. Produzido pela TV Cultura, voltou a ganhar destaque no cenário cultural do país em 2014, quando completou 20 anos de existência, com exposições, novas peças teatrais e matérias nos veículos de comunicação. Este trabalho traz panoramas sobre o histórico e exemplos recentes de jornalismo para crianças – inclusive nas universidades – e a produção de conteúdo infantil na TV, Internet, cinema, rádio, música, literatura, HQs e teatro. Também apresenta resumos dos principais programas infantis da TV Cultura antes e depois do Castelo. Sobre a série, abordam-se detalhes dos personagens, quadros e cômodos do recinto, bem como produtos antigos e recentes frutos da atração. A análise aponta elementos que possam auxiliar o jornalismo para a garotada e com ela. Destacam-se seis tópicos: assunto de criança; o papel do jornalista; apuração e descoberta; brincar; sons; criança quer falar. Utiliza-se o entendimento de comunicação como construção de vínculos, segundo Baitello Junior. O conceito de ecologia da comunicação, conforme Romano, baseia a reflexão sobre práticas comunicacionais que envolvem a meninada. Compreende-se o campo da educomunicação a partir de Soares. E as ideias de Leão sobre hipermídia ajudam a esboçar um exemplo de aplicação dos resultados
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44

Bryta mot reglerna för att göra sitt jobb? : En kvalitativ vinjettstudie i socialsekreterarens moraliska resonemang och handlande

Hamne Jederlund, Moa January 2018 (has links)
I denna studie undersöks socialsekreterarens moraliska värderingar och resonemang i en situation där polis kräver henne på sekretessbelagd information om en klient med utvisningsbeslut. Studien är genomförd med en kvalitativ vinjettmetod där 10 respondenter, samtliga yrkesverksamma socialsekreterare, tagit del av ett fiktivt fall och utifrån detta besvarat ett tiotal frågor kring värderingar, dilemman och beslutsfattande. Data har analyserats med hjälp av en innehållsanalys. Analysen har genomförts genom Zygmunt Bauman och Tim May ́s  teori om ansvar och moraliskt handlande samt Simone de Beauvoirs teori om människans utövande av frihet. Resultatet visar att samtliga respondenter ställer sig kritiska till polisens order samt upplever en konflikt mellan personliga värderingar och arbetsplikt. Majoriteten uppger att de skulle sätta sina personliga värderingar åt sidan och i första hand agera utifrån vad de anser vara arbetsplikten. Flertalet beskriver samtidigt kompromissande strategier, där deras personliga värderingar får ta plats genom tysta och individuella motståndsstrategier, för att på så vis kringgå det upplevda moraliska dilemmat. Resultatet visar sammanfattningsvis på en stor variation i socialsekreterarens handlande och uppfattning av personligt och yrkesmässigt ansvar, samt upplevelse av frihet. / In this study, the social worker ́s moral values and reasoning are investigated in a situation where the police require her to handle out secret classified information about a client with deportation decisions. The study was conducted with a qualitative vignette method in which10 respondents, all working social workers at the social services, responded to a fictitiou scase, answering ten questions about values, dilemmas and decision-making. Data has been analyzed using a content analysis. The analysis was carried out through Zygmunt Bauman and Tim May's theory of man ́s moral action as well as Simone de Beauvoir's theory of man'sexercise of freedom. The result shows that all respondents are critical to the police's orders and they all experience a conflict between personal values and work obligations. The majority state that they would put aside their personal values and primarily act on basis ofwhat they consider to be the duty to work. at the same time the majority describe compromising strategies, where they let their personal values take place through silent and individual resistance strategies, in order to bypass the perceived moral dilemma. Inconclusion, the results show a great variation in the social workers actions and perception ofpersonal and professional responsibility and their freedom.
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45

O poder vai dançar de Tim Robbins: história, avanços e limites / Cradle will rock by Tim Robbins: history, advances and limits

Neyde Figueira Branco 19 April 2011 (has links)
Esta pesquisa se utiliza do filme O poder vai dançar (Cradle will rock, 1999), dirigido por Tim Robbins, para entender a História, os avanços e limites de dois momentos históricos: a década de 1930 e a de 1990 nos Estados Unidos. Definido como uma história predominantemente verdadeira, o filme apresenta personagens e fatos reais e fictícios, que se alternam e se relacionam. Ele é composto por uma série de narrativas, aparentemente fragmentadas e desconexas, mas cujas relações são construídas em todo o seu decorrer. De modo geral, podemos dizer que o filme retrata a década de 1930, momento de potencial revolucionário na História dos Estados Unidos, uma vez que a crise econômica potencializou e tornou visíveis os problemas decorrentes do sistema capitalista. Em seu intento, o diretor se aproxima da concepção benjaminiana de História, à medida que, mais do que simplesmente reproduzir a narrativa desse período, opta por se apropriar de um momento explosivo do passado, carregado de elementos em comum com o presente, e utilizar a citação do passado como fonte de inspiração no combate presente. Ou seja, parte desse passado para na verdade dizer algo sobre a realidade em que está inserido, da década de 1990. Assim, ao pensar sobre esses contextos históricos, nos possibilita refletir sobre suas características, motivações e conseqüências. Para tanto, Tim Robbins se utiliza de elementos do teatro épico, e não apenas retrata os elementos históricos do período, mas busca principalmente provocar uma reflexão por parte da audiência. E tal reflexão vai além do entendimento da história, avança sobre questões como o reconhecimento pelo artista de sua condição de proletário da cultura e sobre o limite que se coloca entre fazer arte paga por empresas e a prostituição, entre outras. / This research makes use of the movie Cradle will rock (1999), directed by Tim Robbins, to understand the History, progresses and limits of two historical periods: the decades of 1930 and 1990 in the United States. Defined as a (mostly) true story, the movie presents real and fictional characters and facts, which are alternated and connected to each other. It has a series of narratives, aparently fragmented. However, its connections are built in the course of the movie. In general, we can say that the film portrays the decade of 1930, moment of revolutionary potential in the History of the United States, as a result of the economical crisis, that made visible all the problems deriving from the capitalistic system. In his intent, the director approaches the conception Benjamin has of the History, as he chooses to go beyond than only narrate the facts of the period and decides to appropriate of such an explosive moment of the past, replete of elements in common with the present, and use the citation of the past as a source of inspiration in the current battle. That is, uses the past in order to say something about the reality he experiences in the decade of 1990. In this manner, we can consider these historical periods and reflect on its characteristics, motivations and consequences. In order to do that, Tim Robbins makes use of elements of the epic theater, and not only depicts the historical elements of the period but also tries to provoke the audience and make them reflect about the facts and elements he exposes. These reflections surpass the understanding of the History and reaches questions such as the recognition of the artist of his condition of proletarian of the culture and the limit between making art sponsored by companies and the prostitution of the artist, among other.
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46

"How to tell a true war story": representation in late twentieth century war narratives.

January 2010 (has links)
Chan, Sze Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 167-172). / Abstracts in English and Chinese. / Abstract --- p.I / List of Illustrations --- p.IV / Acknowledgements --- p.V / "Introduction ""Regarding the Pain of Others"": War as Spectacle today" --- p.1 / Chapter Chapter 1 --- "From ""We Bombed in New Haven"" to bombing our new ""haven"": Joseph Heller's War Play of Metatheatre against Spectators" --- p.27 / Chapter Chapter 2 --- "From ""Society of Spectacle"" to Society of Impotence: Tim O'Brien's War Novels of Affect against Spectator-readers" --- p.56 / Chapter Chapter 3 --- "The War Photographer as the exemplary Spectator in disguise: False ""Witness"" of the Photographic Eye" --- p.104 / Conclusion --- p.150 / Endnotes --- p.157 / Bibliography --- p.167
47

Alice in Wonderland da literatura para o cinema: um estudo da traduÃÃo da era vitoriana e do nonsense literÃrio de Lewis Carroll para o cinematogrÃfico no estilo burtoniano. / Alice in Wonderland from literature to cinema: a study of Lewis CarrollÂs Victorian era translation and literary nonsense to film language in BurtonÂs style

NatÃlia Sampaio Alencar Lima 30 August 2016 (has links)
nÃo hà / Esta pesquisa busca analisar os elementos utilizados por Tim Burton para representar a Era Vitoriana atravÃs do figurino, meio de transporte e decoraÃÃo. Trabalharemos tambÃm com a traduÃÃo em imagens do nonsense em sua adaptaÃÃo fÃlmica Alice in Wonderland (2010). Nessa perspectiva, o presente trabalho resulta de um estudo comparativo entre o filme e a obra na qual se baseia, o cÃnone da literatura infantil Aliceâs Adventures in Wonderland de Lewis Carroll (1865). Para tanto, faremos um cotejo entre as duas obras à luz das teorias de Elizabeth Sewell (2015), Wim Tigges, (1988) e Susan Stewart (1980) que alicerÃam o gÃnero literÃrio nonsense. LanÃaremos mÃo da versÃo literÃria Lewis Carroll: The Complete Fully Illustrated Works de 1995 da editora Gramercy, contendo toda a obra de Lewis Carroll com ilustraÃÃes originais. Isso, a fim de viabilizar e facilitar a comparaÃÃo com as figuras presentes no texto literÃrio, quando necessÃrio, para investigar se houve aproximaÃÃo na representaÃÃo visual feita pelo diretor.
48

"Programas Educativos de Televisão para Crianças Brasileiras: Critérios de Planejamento Proposto a partir das Análises de Vila Sésamo e Rá Tim Bum" / Educational television programs for Brazilian children: proposed planning criteria based on the analysis of Vila Sésamo and Rá Tim Bum

Adriana Maricato de Souza 12 December 2001 (has links)
A história de dois programas infantis de grande repercussão no Brasil, Vila Sésamo (TV Cultura-TV Globo/1972) e Rá Tim Bum (TV Cultura/1990), indica quais são as características da produção educativa brasileira. Eles apresentam um conflito estrutural entre o método de planejamento educacional, de origem norte-americana, e o repertório cultural dos produtores e do público-alvo. A representação deslocada de infância, relações sociais e Educação dos programas educativos comprometeriam seu impacto sobre o público-alvo. Buscando estabelecer quais os critérios mais adequados para programas educativos nacionais, sugere-se a incorporação da perspectiva de Paulo Freire sobre Comunicação e Educação pelas produções brasileiras. Para Freire, o processo educativo se desenvolve a partir do repertório cultural do educando e o estimula a transformar seu ambiente. Num momento de consolidação da democracia na América Latina, entende-se educar através da televisão como construção simbólica e prática da cidadania, onde produtores e receptores dialogam e se reconhecem como sujeitos do mesmo processo social. Planejar programas com estes propósitos requer a criação de parâmetros a partir da prática da produção cultural no país e da realidade objetiva do público-alvo. Este trabalho sugere critérios básicos para futuras produções de produtos educativos dirigidos às crianças brasileiras, em contraposição ao condicionamento para o consumo proposto pelos programas importados, tidos equivocadamente como educativos. / The history of two children programs of strong impact in Brazil, Vila Sésamo (TV Cultura-TV Globo/1972) and Rá Tim Bum (TV Cultura/1990), points out what the Brazilian educational production characteristics are. They show a structural conflict between the educational planning method of Northern American origin and the producers’ and target audience’s cultural background. Aimed at establishing the most adequate criteria for national educational programs, it is suggested that Paulo Freire’s perspective on Communication and Education by the Brazilian productions be incorporated. To Freire, the educational process starts from the learner’s cultural background and it stimulates him/her to transform his/her environment. At a democracy consolidation moment in Latin America, education through television is understood as symbolic and practical construction of citizenship, where producers and viewers dialogue and recognize themselves as agents in the same social process. Planning programs for educational purposes requires the creation of parameters departing from the country’s cultural production practice and from the target audience’s objective reality. This dissertation suggests basic criteria for making future educational products aimed at Brazilian children, which are opposed to the consumerism conditioned by imported programs mistaken as educational.
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49

Tim O'Brien : l'écriture de la hantise / Tim O’Brien : Writing on What Haunts

Kowalczuk, Barbara 25 November 2016 (has links)
Cette hantologie de l’œuvre o’brienesque dépasse le postulat selon lequel Tim O’Brien est un écrivain de la guerre du Vietnam. S’il est indéniable que l’expérience personnelle du combat a influé sur la fiction et la non-fiction de l’auteur, les récits sont avant tout marqués par la hantise, au sens géographique, spatial et psychique du terme. La psychologie des lieux investis ou remémorés par l’auteur, les narrateurs et les protagonistes, est associée à des événements marquants dont on retrouve la trace dans le corps, la mémoire individuelle et collective, ainsi qu’au niveau formel. De fait, les êtres sont habités par la hantise timérique, le poids de la perte ou les séquelles de la traumatisation. O’Brien souligne l’appréhension, l’obsession, la mélancolie et les revenances traumatiques dans des thanatographies pénétrées de spectres et de fantômes, tout autant de manifestations de restances qui ne cessent de faire retour. La fréquentation des mêmes lieux, leur pouvoir hantologique, ainsi que la symbolisation du hantement psychique constituent une habitation thématique dont l’ascendance est perceptible d’un point de vue structurel et stylistique. Par conséquent, le texte o’brienesque se fait à son tour hantise : un lieu scriptural où l’auteur se spectralise, (re)visite d’autres écrivains et sa propre discursivité. L’ambiguïté née de l’autofictionnalisation et de l’énigmatisation, la configuration métafictionnelle ou métanarrative, enfin la tension narrative, ont pour effet de générer des textes intrigants et autoréflexifs. Au terme de l’analyse, il apparaît qu’O’Brien compose une spectropoétique ancrée dans un hantissage empreint d’une sensibilité baroque et d’une quintessence thanatologique qui assurent à l’auteur l’immortalité symbolique. / While critics tend to consider Tim O’Brien as a writer of the Vietnam War, this hauntology of the author’s works goes beyond such postulate. Though it is indisputable that the personal experience of combat has influenced O’Brien’s fictional and non-fictional writing, the latter primarily deals with haunting, in the geographical, spatial and psychological sense of the term. The places visited or remembered by the author, the narrators and the protagonists, are associated with unforgettable events, lingering memories and reviviscences that can be traced in the body, in individual and collective memory, as well as in the form of the texts. Thus, individuals are haunted by disquietude, loss or the side effects of traumatization. O’Brien stresses apprehension, obsession, melancholy and traumatic revivification in thanatographies penetrated by specters and ghosts that keep returning. The hauntological power of geographical, spatial and psychological haunts establishes a recurring theme that impacts structure and style. Therefore, the o’brienesque text becomes a haunted and a haunting space, marked by the spectrality of the author. O’Brien (re)visits other writers and his previous writings. Ambiguous and enigmatic utterances, metafictional or metanarrative configurations and narrative tension generate intriguing and self-reflexive texts. In the end, it appears that O’Brien’s spectropoetics reads like a hantissage imbued with baroque traits and thanatological quintessence that provide the author with symbolic immortality.
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50

Protein crystallographic studies of A-TIM—structure based development of new enzymes

Salin, M. (Mikko) 09 March 2010 (has links)
Abstract Enzymes are potentially superior as catalysts for many industrial chemical processes because of their high specificity, selectivity, minimum energy requirement and environmental friendliness. However, many challenges remain in order to exploit fully the potential of industrial enzymes. The qualities which are needed are catalytic proficiency, availability in high quantities, low price, low product inhibition, and high activity and stability under process conditions. Directed evolution and rational design are the most common strategies to produce enzymes with the desired properties. The TIM barrel is the most frequent and most versatile fold among naturally occurring enzymes. In all known TIM barrel enzymes, the catalytically active residues are located at one end of the barrel structure, while residues maintaining the stability of the fold are found on the opposite end of the barrel. This special architecture of the TIM barrel proteins makes it possible to change catalytic activity of the protein without compromising its stability, which is a perfect start for protein engineering studies. In this research project, a monomeric triosephosphate isomerase (TIM) variant with an engineered binding groove (A-TIM) was created by using a rational design approach. The major aims of this work were (i) to find novel binders and (ii) characterize the new, bigger binding groove using X-ray crystallographic methods. These studies have discovered that monomeric A-TIM can bind compounds completely different from the natural substrate. Studies on three different classes of binder molecules are reported: (i) true substrate analogues of wild type TIM, (ii) substrate analogues that have an extended hydrophobic tail, and (iii) more extended, phosphate containing substrate analogues. In addition to this, the A-TIM active site was shown to be competent. In general these studies illustrate the importance of protein crystallography for characterizing the binding properties of enzyme variants being studied in enzyme discovery projects. / Tiivistelmä Entsyymit voivat toimia ylivoimaisina katalyytteinä monissa kemianteollisuuden prosesseissa johtuen niiden hyvästä spesifisyydestä, valikoimiskyvystä, alhaisesta energiantarpeesta ja ympäristöystävällisyydestä. Näistä ominaisuuksista huolimatta entsyymien kaikkien mahdollisuuksien hyödyntämisen esteenä on monia haasteita. Tarvittavia ominaisuuksia ovat katalyyttinen tehokkuus, saatavuus suurina määrinä, alhainen hinta, alhainen tuoteinhibitio sekä korkea aktiivisuus ja stabiilisuus prosessiolosuhteissa. TIM-tynnyrirakenne on yleisin ja monipuolisin proteiinien laskostumisrakenne luonnossa esiintyvissä entsyymeissä. Tässä rakenteessa katalyyttisesti aktiiviset aminohappotähteet ovat sijoittuneet tynnyrirakenteen toiselle puolelle, kun taas stabiilisuuden kannalta tärkeät aminohappotähteet ovat sijoittuneet kokonaan toiselle puolelle. Tämä erityinen rakenne antaa mahdollisuuden muokata proteiinin katalyyttistä aktiivisuutta vaikuttamatta haitallisesti sen stabiilisuuteen. Tämä on täydellinen lähtökohta proteiininmuokkaukselle. Tässä tutkimusprojektissa käytettiin ns. järkiperäistä suunnittelua monomeerisen trioosifosfaatti-isomeraasivariantin (A-TIM) luomisessa. Tämän tutkimustyön pääasialliset tavoitteet olivat (i) uusien sitoutujien löytäminen ja (ii) uuden, suuremman sitoutumistaskun ominaisuuksien määrittäminen röntgenkristallografisilla menetelmillä. Tässä tutkimuksessa havaittiin, että A-TIM kykenee sitomaan yhdisteitä, jotka ovat täysin erilaisia luonnolliseen substraattiin verrattuna. Tässä tutkimuksessa kuvaillaan kolmenlaisia sitoutujia: (i) todelliset villityypin entsyymin substraattianalogit, (ii) substraattianalogit, joihin on liitetty hydrofobinen hiilivetyketju ja (iii) villityypin substraattia suuremmat sokerifosfaatit. Tämän lisäksi A-TIM:n aktiivisen keskuksen todistettiin olevan toimintakykyinen. Yleisellä tasolla tämä tutkimus osoittaa röntgenkristallografisten menetelmien tärkeyden entsyymienmuokkausprojekteissa, joissa entsyymivarianttien ominaisuuksien määritys on tärkeää.
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