More than 27 million people have been forced to leave their homes and have sought refuge in another part of their home country. Since they have not crossed an internationally recognized state border, they do not enjoy the same protection as refugees. The Westphalian principle of state sovereignty does not allow the international community to get involved and protect IDPs, as long as this intervention is not explicitly requested by the government. This paper defines internal displacement, shows its causes, and explores mechanisms to cope with the difficult situation of the internally displaced. A case study on the conflict in Darfur puts these issues into the real context of a complex humanitarian situation. The conflict in Darfur is an ethnic clash between the Arab supremacists in the Sudanese capital Khartoum and the African population in Darfur, which has existed since the 1980s and reached its climax in the past decade. The conflict has been the cause of one of the severest displacement tragedies considering the fact that the largest part of Sudan's more than five million IDPs are displaced in Darfur. The government has shown little interest in cooperating with the international community to assist civilians in Darfur, but is, on the contrary, generally suspected to be involved in the...

This research explores the process of integration of IDPs into the host communities in Ukraine from Communication for Development perspective. It aims to examine integration process in the context of representation and participatory communication theories. The objectives of this research are threefold. Firstly, it explores the concept of “successful” or finalized integration. Secondly, it investigates existing stereotypes and myths about IDPs in Ukrainian society through the lens of representation theory. Thirdly, it examines promising participatory communication projects in Ukraine aimed at countering these stereotypes. The research is based on semi-structured interviews with IDPs, representatives of host communities, employees of international development organizations and NGO, producer of TV-show and the author of the performance about IDPs. The research finds that establishment of social contacts and engagement into the life of the new community is key to successful integration and that stereotyped perception of IDPs in Ukrainian society comes not from interpersonal experience, but from media and political context and more participatory communication projects are needed for countering it.

Il a récemment été rapporté que l'interaction physiologique entre la protéine nucléaire SMRT et le facteur de transcription cellulaire STAT3 pouvait être rompue par la protéine EBNA2 du virus Epstein-Barr (EBV). La liaison de SMRT à STAT3 diminue son activité de transcription. EBNA2 libère SMRT de ce complexe augmentant ainsi la transcription des gènes régulés par STAT3. STAT3 régule de nombreux effets immunodépresseurs mais aussi anti-prolifératifs et anti-apoptotiques dans l'organisme hôte, et pourrait jouer un rôle important dans la stratégie de survie du virus Epstein-Barr. EBNA2 et STAT3 sont tous deux intrinsèquement désordonnés (IDPs) comme un tiers de toutes les protéines eucaryotes et 70% des protéines associées aux cancers. Toutefois, malgré leur abondance, notre compréhension de leurs fonctions reste limitée notamment à cause de la difficulté à les produire en quantités suffisantes pour réaliser des études structurales et biophysiques. Afin de surmonter cette difficulté, la technologie ESPRIT a été utilisée pour générer des fragments de SMRT et EBNA2 solubles et stables. Ces fragments se répartissaient sur une grande partie des gènes d'EBNA2 et SMRT pour lesquels les protéines exprimées étaient de tailles compatibles avec des expériences de RMN. Ceci a permis de réaliser des études d'interaction avec STAT3. Les deux protéines étant majoritairement intrinsèquement désordonnées, toutes les données d'interaction ont été analysées pour EBNA2 et SMRT avec une attention particulière sur les propriétés de protéines désordonnées. Des fragments des deux protéines, EBNA2 et SMRT, ont été soumis à des tests d'interaction avec le dimère de STAT3 en utilisant des méthodes biophysiques variées. Ainsi la cinétique de liaison et la séquence d'acides aminés impliqués dans l'interaction ont pu être déterminées. Etant donné son importance biologique et son interaction de haute affinité, l'accent a été porté sur l'interaction EBNA2-SMRT. Ainsi des résultats préliminaires provenant d'investigations en cellules de mammifères ont pu être obtenus. En outre l'interaction entre EBNA2 et d'autres protéines cellulaires a été brièvement étudiée. Les résultats obtenus ont pour objectif d'améliorer notre compréhension de la stratégie avec laquelle EBV parvient, avec succès, à persister toute une vie dans l'organisme hôte. / It was recently reported that the physiological interaction between the nuclear protein SMRT and the cellular transcription factor STAT3 could be disrupted by the Epstein-Barr-virus protein EBNA2. Binding of SMRT to STAT3 decreases its transcriptional activity. EBNA2 releases SMRT from this complex and therefore enhances the transcription of both host and viral STAT3 regulated genes. STAT3 regulates several immunosuppressive as well as pro-proliferative and anti-apoptotic effects in the host organism and so may have importance for the viral survival strategy of Epstein-Barr-virus. Both EBNA2 and SMRT are intrinsically disordered proteins (IDPs) in common with about one third of all eukaryotic proteins and 70% of cancer-related. Despite their abundance, our understanding of how they function is limited, in part due to difficulties in production of stable samples in the large quantities necessary for structural and biophysical studies. The EPRIT technology was used to overcome these problems and generate well-behaving and -expressing EBNA2 and SMRT fragments. These fragments covered large parts of the EBNA2 and SMRT genes and were in a suitable size for NMR experiments. This enabled interaction studies of these proteins with STAT3. As both proteins are mainly intrinsically disordered all interaction data were analysed with attention to the disordered properties of both proteins. In order to complement the interaction data all fragments used for the interaction studies were as well characterized as IDPs using biochemical and biophysical methods. Fragments of both proteins, EBNA2 and SMRT together with the STAT3 dimer were subjected to binding analysis using various biophysical methods. The kinetics of the binding could be determined and the binding regions could be narrowed down to the amino acid level. Because of its biological significance and higher affinity interaction the EBNA2-STAT3 part was prioritized and first preliminary results investigating the interaction in mammalian cells could be obtained. Also, the interaction between EBNA2 and other cellular proteins was studied briefly. The obtained results aim to improve our understanding of how EBV succeeds to persist lifelong in the host organism.

Armed hostilities and conflicts have not only killed hundreds of thousands, but have alsodisplaced millions of families and communities around the world, forcing them to move out oftheir homes and seek shelter somewhere else. Some have crossed borders and sought refuge inother countries (refugees). Internally displaced peoples (IDPs) are those victims of conflict whohave remained within their own countries, suffering from constant displacements and numerousviolations to their human rights. However, they are not mere helpless victims of conflict anddisplacement, but instead some of them are also heralded as heroes because of their activeparticipation in and contributions to the peace process. Already viewed both as victims andheroes, this qualitative desk study looks at a third perspective to the IDP community: can theyalso be seen as potential spoilers to peace processes? An analytical framework outlining some conditions to spoiling activities and behaviour has beendeveloped in this study as a basis to facilitate research into this topic. The framework is thenapplied to a case study, chosen because of its community’s heterogeneity: the IDPs of Mindanao,also known as the Bakwit. Through consulting previous research and current relevant newsreports on the Bakwit, their opinions and attitudes toward the conflict, their proposed solutions toending the conflict, as well as, their role in the peace process in Mindanao are discussed in thisstudy. With the application of the analytical framework on the case of the IDPs in Mindanao, thisresearch has found out that because of their direct involvement in conflict, limited politicalparticipation, and limited socioeconomic inclusion, the Bakwit has the potential to spoilingactivities and behaviour. Their exposure to majority of the conditions and characteristics thattrigger spoiling behaviour could hinder them in participating in the peace building process. Thus,the analytical framework has also been used to conclude what governments and the internationalcustodians can do to prevent IDPs from engaging in spoiling activities and to ensure that conflictresolution, negotiations, and peace building activities are more sustainable.

The RecQ family of helicases has been termed the “Caretakers of the Genome,” and rightfully so. These proteins are highly conserved from bacteria to humans and have been implicated in functions from homologous recombinatorial repair to damage checkpoint response to telomere maintenance and more. Mutant genes of three of the human RecQ helicases lead to syndromes characterized by a high incidence of cancer, premature aging and early death. Despite their implications in several biological functions and importance to the integrity of the human genome and suppression of cancer, many aspects of the RecQ family structure and function remain unknown. To date, much is known about the catalytic function of the helicase domain and accompanying domains, but considerably less is known about the non-catalytic N-terminus in these proteins, which, in many cases, including those human orthologs involved in disease, can make up about half of the total protein length. While experiments have been able to identify protein partners that interact with the N-terminal region, few are able to narrow the binding sites to minimally functional parts and fewer still describe any detail regarding the structural features of these binding areas. In fact, some reviews have generally described the N-terminus as “featureless,” a concept we challenge in our studies. Many of the N-termini of these RecQs have long been known to contain large stretches of acidic residues, a feature of intrinsically disordered regions. These regions/proteins are rich in charged and polar residues, lack compactness that makes crystallography possible, and have flexible and dynamic conformations that are prevalent in “high specificity, low affinity” interactions. Disordered proteins are well-known to be hot spots for protein/protein interactions and post-translational modifications, amongst other functions. Considering these facts, and recognizing the ties between these and what we know about the N-termini of the RecQs, we hypothesized that these proteins likely have long disordered termini. In Chapter 3, we confirm the presence of disorder at the Top3/Rmi1 binding site on Sgs1, the Saccharomyces cerevisiae RecQ helicase. We show that even in a disordered state, this binding region is not “featureless,” but in fact contains a transient alpha-helical molecular recognition element that is necessary to facilitate complex formation between Sgs1, Top3 and Rmi1. Loss of helical structure at this site leads to increased genomic instability and sensitivity to DNA damaging agents. Based on these results, we suggest that there are likely many more such elements in the N-terminus that that are important for other Sgs1 protein/protein interactions and provide an estimate for the number of interactions in this region. In Chapter 4, we evaluate the prevalence of disorder in a set of Chromatin Processes proteins in an effort to establish a role for disorder with regards to maintaining chromatin integrity. In our bioinformatics study, we found that disorder is overrepresented in the Chromatin Processes proteins, and that a major driving force for disorder in these proteins is protein/protein interaction and post-translational modification. We also show a biological connection to disorder and increased protein/protein interaction by investigating these parameters in the context of the DNA damage checkpoint response and in complex formations. Mediators between highly structured kinases in the checkpoint were the most interactive proteins and over half of all predicted interaction sites occurred in disordered areas. Complexed proteins often contained one protein with a high number of disordered sites and a high number of predicted interactions, while the rest were considerably more ordered. Chapter 5 explores a Sgs1 interaction partner, Rmi1 and uses bioinformatics to design structurally-based point mutations in an effort to further elucidate Rmi1 function in yeast, which remains largely unknown outside of its enhancement of Top3/Sgs1 catalytic function. Using AGADIR, which predicts alpha-helical structure and is particularly useful in our hands for guided-mutagenesis in disordered regions, we identified several point mutations that lead to Δrmi1 phenotypes or intermediate growth on hydroxyurea. We hypothesize that these mutants are important in maintaining Rmi1 stability. Together, these studies suggest an important change in how the field approaches further studies into the RecQ helicases; traditional methods of primary sequence comparisons and crystal structures limit the study of disordered regions that are still functionally important. Future care should be given to consider the conservation of structure or structural elements in the RecQs over strict alignments when comparing functional regions between orthologs. Our studies also suggest that it is highly likely that structural motifs for important protein interactions in RecQs are being overlooked because they are not readily obvious using traditional methods. By understanding these motifs and the interactions they facilitate, we may be able to more easily identify polymorphisms in patients with genomically unstable conditions like cancer and, having better understood the biological process these structures facilitate, design drugs to counteract detrimental effects.

The increasing impacts of climate change bear new challenges for the international community. The exacerbation of natural disasters in frequency and scope also confronts the national governments with newly arising problems. Disaster-induced displacement isan increasing phenomenon occurring the last years, which particularly vulnerable regions with a high exposure to national hazards are affected by. The present study addresses the inclusion of disaster IDPs in Disaster Risk Reduction frameworks on international and national level and argues that there is a need to recognize disaster-induced displacement as an increasing issue that should explicitly be addressed and included in policy frameworks on both levels. This was addressed through analyzing international and national key strategies in Disaster-Risk-Reduction. A case comparison of the earthquake in Haiti in 2010 and the yearly recurring floods in Mozambique since 2000 illustrates the implementation of these frameworks in regard to the issue of displacement. Although efforts have been made on both levels to improve the situation of IDPs in the response and recovery phase, it is argued that an inclusion through a community-based approach is needed in all the phases of disaster management to appropriately address the needs of disaster IDPs in the pre-and post-disaster phases.

This study explores how Donbass IDPs in Kyiv view the role of the state in relation to ‘durable solutions’ to their displacement. Specifically, it examines the expectations on the state as a provider of rights and entitlements vis-à- vis IDPs. Drawing on semi-structured interviews with Donbas IDPs, experiences of displacement and perceptions of durable solutions and citizen-state relations are exemplified. The data collection and analysis methodologies applied allow for the elicitation of the views and opinions of IDPs, in an attempt to mitigate vertical policy-making. The concepts of citizenship, state and sovereignty are applied to analyze the relationship between IDPs and the state. Further, the IASC framework for durable solutions to internal displacement is used to as a structure to outline the views of the IDPs. The results show a large discrepancy between the expectations of the respondents on the states’ role in durable solutions to displacement, and the experience of this in reality. Furthermore, the results reveal high levels of discontent, resignation and apathy towards the state as a provider of durable solutions, especially in terms of returning to Donbass.

After the WWII, there was much concern to protect human rights situation all over the world. During the cold wars, huge displacement took place within different countries due to internal arms/ethnic conflicts. Millions of IDPs, who were uprooted by armed conflict or ethnic strife faced human rights violence. In 2002, there were estimated between 20-25 millions IDPs in the world (Phuong, p.1). Internally displacement is a worldwide problem and millions of the people displaced in Africa and Asia. These all Internal displacements of the people are only the result of the conflicts or the violations of the Human Rights but also sometimes it happened because of the natural disasters. “All human beings are born free and equal in dignity and rights..."(Streich, Article 1) This article works as the foundation of human rights which gives every human being an equal rights and opportunity to maintain his/her dignity. Human Rights issues related to human dignity must be taken very seriously and should not be ignored at any level; Many human rights issues are not always visible, issues such as: privacy, security, equality, protection of social and cultural values etc. In this paper I am going to apply theoretical approach of “all human being are equal in dignity and rights” to defend IDPs rights.

Les IDPs sont des protéines dépourvues de structure 3D unique en solution et en l'absence de leur(s) partenaire(s). Ces protéines possèdent des propriétés d'interactions avec leurs partenaires uniques.L'extrêmité C-terminale de la nucléoprotéine du virus de la rougeole, NTAIL, est une IDP. NTAIL interagit avec XD, le domaine C-terminal globulaire de la phosphoprotéine virale, via la box2 qui est un a-MoRE. Cette interaction permet le recrutement de la protéine L afin de former la polymérase virale.J'ai pu montrer que la contribution des différents résidus au sein de l'a-MoRE dépend de l'orientation de leur chaîne latérale, et que la substitution d'un seul acide aminé crucial a des effets dramatiques sur la réplication virale.Les IDPs conservent un désordre résiduel non négligeable au sein du complexe. Cela se manifeste par la présence des régions « fuzzy » de part et d'autres du MoRE. Nous avons montré que la région « fuzzy » en amont de la box2 inhibe l'établissement de l'interaction entre NTAIL et ses partenaires.Lors de l'interaction avec leurs partenaires les IDPs subissent en général un gain de structure. Le repliement associé à l'interaction peut avoir lieu avant ou après interaction. Des études précédentes ont montré l'existence d'une pré-structuration partielle de l'alpha-MoRE de NTAIL. L'interaction entre NTAIL et XD a été étudiée et a permis de conclure que NTAIL se replie selon un mécanisme de repliement induit.Dans leur ensemble, ces études contribuent à éclaircir les mécanismes moléculaires qui gouvernent la reconnaissance de partenaires par les IDPs. / IDPs are proteins devoided of a unique and stable 3D structure in solution and in the absence of their partners. Those proteins possess unique properties, as well as mechanisms of interaction with their partners.The C-terminal region of the nucleoprotein of measles virus, NTAIL, is an IDP and interacts with XD, the globular C-terminal domain of the viral phosphoprotein, via the box2 region that is an (alpha-MoRE). This interaction allows to recruit the L protein in order to form the viral polymerase.The aim of my work was to characterize the molecular basis of NTAIL-XD interaction. I was able to show that the contribution of the amino acids among box2 depends on the orientation of their lateral chain, and that the substitution of one single amino acid has drastic effect upon the viral replication.IDPs keep a non-negligible amount of residual disorder among the complex. This fuzziness can have multiple forms, like the presence of fuzzy regions from either side of the MoRE. The impact fuzzy regions have within the complex is not well known. We demonstrated that the fuzzy region upstream box2 inhibits the settlement of the interaction between NTAIL and its partners.When interacting with their partners, IDPs generally undergo a folding associated with binding that can take place either before or after the interaction. The interaction between NTAIL and XD was investigated and monitored by fluorescence kinetic measurements, using variants bearing a tryptophan substitution. We concluded without any doubt that NTAIL folds under an induced folding mechanism.Those studies together contribute to enlighten the molecular mechanisms that govern partner recognition by the IDPs.

COR15A is a cold regulated disordered protein from Arabidopsis thaliana that contributes to freezing tolerance in plants by protecting membranes. It belongs to the (LEA) Late Embryogenesis Abundant group of proteins that accumulate during the later stage of seed development and are expressed in various parts of the plant. During freezing-induced cellular dehydration, COR15A transitions from a disordered structure to a mostly α-helical structure that binds and stabilizes chloroplast membranes when cells dehydrate due to freezing. We hypothesize that increasing the transient α-helicity of COR15A under normal conditions will increase its ability to bind and protect chloroplast membranes when cells are frozen. To test this hypothesis, conserved glycine residues were mutated to alanine to increase α-helicity. NMR spectroscopy was used to examine structural changes of these mutants compared to wildtype in 0% and 20% TFE. The impact of these mutations on the stability of model membranes during a freeze-thaw cycle was investigated by fluorescence spectroscopy. The results of these experiments showed the mutants had a higher content of α-helical secondary structure than wildtype in 0% and 20% TFE. Increased α-helicity of the COR15A mutants improved membrane stabilization during freezing. Altogether, our results suggest the conserved glycine residues are important for maintaining the disordered structure of the protein.