GUPEA

Gothenburg University Publications Electronic Archive

GUPEA is a platform for e-publishing of theses, student essays and other research publications.

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  • Bröderna Grimms sagor /
    (1897) Grimm, Jacob,
  • Harnessing Covalent Chemistry for Targeted Protein Labelling: A BTK Story
    (2026-01-16) Anna Valaka
    Labelling of proteins in live cells is of great importance to study protein function, dynamics, and interactions in complex biological systems. Ligand-directed chemistry techniques enable the chemical modification of proteins in live cells without compromising enzymatic activity. Bruton’s tyrosine kinase (BTK) is a validated oncology target that plays a central role in B-cell proliferation and activation. Many existing covalent probes irreversibly inhibit BTK, limiting their utility for functional studies in living cells. This thesis aimed to develop activity-preserving covalent probes for BTK and to investigate covalent chemistry more broadly in the context of warhead reactivity and assay development. Ligand-directed covalent probes were designed and assessed using BTK as a model system. Fluorescent probes incorporating a methacrylamide warhead enabled labelling of BTK in cells without impairing the enzymatic activity and were applied to study BTK’s dynamic signalling pathway with confocal microscopy. To facilitate tuning of covalent warhead reactivity, an investigation of aromatic sulfoxide and sulfone warheads capable of undergoing nucleophilic aromatic substitution (SNAr) with nucleophiles was conducted. This included variation of aromatic scaffolds, leaving-groupelectronics and sulfur oxidation state. Kinetic assays showed pronounced chemoselectivity towards N-acetyl cysteine, spanning a range of reactivity profiles. Selected warheads were incorporated into BTK-probes, validating predictable labelling behaviour from reactivity in solution to protein assays. Computational studies aided with the design of a selective probe for endogenous BTK labelling which preserved enzymatic activity in cells, while binding assays validated the ligand-release mechanism. This thesis also explores how warhead orientation can influence labelling efficiency by incorporating chirality in the design of an enantiomeric pair of BTK-probes. The otherwise physicochemically equivalent probe pair displayed pronounced differences in activity and their capacity to form a covalent bond with recombinant BTK. The results highlighted the importance of stereoselective protein-ligand interactions, while also underscoring the complexity of translating these effects to cellular systems. To address limitations associated with conventional reactivity profiling methods, a fluorescence based assay was developed to assess intrinsic warhead reactivity. A FRET-based sensor incorporating an SNAr electrophile enabled quantitative kinetic analysis towards different nucleophiles in a high-throughput manner, providing a complementary and scalable approach to traditional analytical techniques. Overall, these findings address key opportunities and challenges in protein labelling and provide useful chemical tools for the design of covalent modalities. Beyond BTK, these tools may be applicable to other protein targets, making an important addition in the chemical biology toolbox.
  • Constructing the Threat, Reconstructing the Self: Russia and Swedish Security Discourse in the NATO Accession Process
    (2026-01-16) Axelsson, Fanny Jane; University of Gothenburg/School of Global Studies; Göteborgs universitet/Institutionen för globala studier
    Sweden’s defence policy has long been defined by a self-image of non-alignment, a tradition spanning over two centuries that emphasises neutrality and avoidance of military alliances. This self-perception is deeply embedded in Swedish national identity. However, rising military tensions in Europe, particularly following Russia’s annexation of Crimea in 2014 and its full-scale invasion of Ukraine in 2022, have challenged this longstanding posture. Sweden’s security environment has shifted, prompting a gradual move toward closer military cooperation, culminating in the decision to join NATO between 2022 and 2024. This thesis explores how Swedish identity as a neutral, non-aligned state is reconstructed within official security discourse during this period of change. Drawing on poststructuralist International Relations theory, the study emphasises the co constitutive relationship between identity and (in)security, analysing how language and discourse shape political subjects and possibilities. It employs Carol Bacchi’s ‘What’s the Problem Represented to be?’ framework to conduct a discourse analysis of Allvarstid (2023), an official security policy report by the Swedish Defence Commission. The findings demonstrate that Russia is discursively constructed as an authoritarian, revisionist and enduring threat, juxtaposed with a Sweden portrayed as democratic, peaceful and rules-based. This binary serves to legitimise Sweden’s strategic departure from non-alignment and entry into NATO, not only as necessary for security but also as morally justified. The report redefines Swedish identity from a neutral outsider to an active, responsible stakeholder in the Euro-Atlantic security order, embedding the alliance within a narrative of shared values and collective responsibility. This thesis shows how security discourse functions as a powerful mechanism for identity rearticulation, illustrating that moments of perceived crisis enable fundamental shifts in national identity construction. By producing new security ‘common sense,’ the discourse foreclosed alternative security arrangements, ultimately reshaping Sweden’s political subjectivity and its place in international security politics.
  • Health Economic Aspects of Cancer Care: Evaluating Evidence for Drug Reimbursement and Screening Programs
    (2026-01-15) Chauca Strand, Gabriella
    To improve population health and ensure value for money, decision-making in health care must rely on transparent and well-informed evaluations of the expected costs and effects of new health interventions. The purpose of this thesis was to generate and evaluate evidence on the clinical effectiveness and cost-effectiveness of interventions introduced within the cancer care pathway to inform future policy discussions and decision-making. The thesis focuses on two areas: reimbursement decisions for cancer drugs and colorectal cancer (CRC) screening in Sweden, using descriptive analysis, econometrics, and health economic modeling. Papers I–II assessed the evidence on clinical effectiveness and cost-effectiveness underlying reimbursement decisions for new prescription cancer drugs, using public decision dossiers and published literature. The findings show that a considerable proportion of reimbursement decisions rely on inconclusive evidence regarding improvements in overall survival (OS) and quality of life (QoL). Paper III–IV evaluated the effectiveness, cost-effectiveness, and inequality impact of organized CRC screening programs in reducing incidence and improving quality-adjusted life years, using secondary literature and registry data. The results indicate that CRC screening effectively improves health outcomes and is cost-effective; however, the benefits are unevenly distributed across socioeconomic groups. In conclusion, the thesis findings imply uncertainty regarding cancer drugs’ value for money and the benefits ultimately realized by patients and society. Furthermore, organized CRC screening reduces disease burden and improves population health; yet it may exacerbate existing socioeconomic inequalities in health.
  • En legitim tronarvinge? Kvinnlig tronföljd, möderne och äkta börd i Norge, 1161–1302
    (2026-01-15) Husvik, Benjamin
    This doctoral thesis concerns the development of female succession in Norway from 1161–1302 in relation to the broader European context. The rationale behind this thesis is twofold. First, structural factors have, in general, been neglected in previous research on the implementation of female succession in Norway in 1302. Second, the development of female succession in Norway has not been examined in relation to the broader European setting. Situating the Norwegian development in a wider European context can help illuminate the role of structural factors in the implementation of female succession in Norway. The investigation of the Norwegian case can also highlight similarities and differences between Norway and Europe with regards to the development of female succession and queenship. The bulk of the thesis focuses on how and why structural factors, particularly legitimate birth and maternal descent, changed in Norway and made the ratification of female succession possible. Focus is specifically put on what value legitimate birth and maternal descent was ascribed as symbolic capital for making claims to the Norwegian throne and how political actors (il)legitimation activities, for example in their power struggles for the throne, altered this value. The consequences of the implementation of female succession for the power of royal women are also examined, particularly whether any potential heiresses could become recognized as a queen regnant. One of the main conclusions reached in the thesis is that changes to structural factors, such as maternal descent, played a crucial role in the implementation of female succession in Norway. This finding is in sharp contrast to previous research, which was mainly concerned with the explanatory power of situational factors in the development, especially that the reigning king Haakon Magnusson lacked male children. Also, this thesis demonstrates that under normal circumstances, Norwegian heiresses would not be recognized as a queen regnant, with the caveat that some potential existed for widows to become female monarchs. This result corresponds with international research about queenship but contrasts with previous research about Norway.