This dissertation is an exploration of the ways in which contemporary practices of pluralism are challenging, and being shaped by, concepts of state sovereignty. I explore two very different contexts; the relationship between First Nations and Settlers on that part of Turtle Island sometimes called Canada, and the relationship between the European Union and its Member-States. In both contexts, I explore how political, legal, and economic practices are generating forms of social order that depart to varying degrees from the total, exclusive authority associated with sovereignty. In particular, I show that actors in both settings have actually developed two remarkably similar practices – interpenetrating institutions or co-decision mechanisms, and conditional authority claims. Together, these practices enable actors to contest and coordinate their respective authority claims in ways that do not rely on an overarching sovereign or even a shared understanding of their relationship. Instead, practices of interpenetration and conditional authority make all parties responsive to multiple standards of conduct, allowing diverse actors to seek justice over time in conditions of persistent difference and conflict. / Graduate

This thesis project explores the question of the death of architecture; the declaration of the lost abilities of architecture to achieve political influence and the architect as a social actor. As I have found myself in agreement with this Tafurian perspective on the subject, I wanted to use this thesis project to explore the question of architecture and its political potential, as well as breaking from the paralyzing condition of the incentives of architecture's incapabilities. This, in suggesting that architecture can act as a catalyst for doing things differently. The project investigates, on the one hand,  how a building can encourage political action and engagement, and, on the other, how ideological ideas and intentions can concretize spatially, materially and aesthetically, The project is an design exploration concretized in a specific architectural proposal – a building for a political organization operating in the city of Stockholm.

No description available.

Sempre s’havia pensat que el concepte religiós i el concepte esportiu pertanyien a dues esferes excloents de la vida de l’ésser humà, dos conceptes vitals contraposats: la vida de l’espiritualitat i la de l`ànima, en contraposició amb una concepció més corpòria de la vida. Per tant, l’atleta de l’esperit i l’atleta del cos no podien conviure plegats en el recorregut vital de les persones. L’aparició del cristianisme, com una escissió del judaisme, es va trobar fortament impregnada d’elements de la cultura clàssica helenística. Com a fil conductor de la tesi doctoral ens centrarem en el pensament de Pau de Tars, cap visible de la comunitat cristiana d’Antioquia. A les seves cartes pastorals va emprar un estil metafòric impregnat d’elements que provenien de la concepció esportivo-afonística que va caracteritzar la “paideia” grega, un mètode pedagògic que unia el desenvolupament de l’intel.lecte amb les pràctiques físico-esportives com a únic camí per a aconseguir la virtut. Creiem que l’herència clàssica al pensament de l’Apòstol quant a la seva concepció agonística de la vida pot incidir de manera positiva en el món del futbol formatiu. Aspectes com l’ascetisme, la negació dels ídols, la professió de fe paulina centrada en l’existència d’un únic Déu han estat alguns dels elements que hem pogut comparar amb el món del futbol contemporani. Les anomenades metàfores esportives paulines centraven un discurs on es feia una crida a la lluita, a l’esforç i a la cooperació que serien presents a la difícil vida dels primers cristians. Atenent a aquests supòsits, en el treball doctoral s’estableixen un seguit de principis axiològics derivats de l’essència del missatge epistolar de Pau i que poden ser utilitzats en la millora de la pedagogia esportiva del futbol fins al punt de poder establir un codi ètic, que pugui ser útil en el terreny de les escoles formatives i també com a eina vàlida per als educadors d’aquest esport. Els elements que van caracteritzar el “corpus paulinum” han estat comparats, en aquest treball, amb trets que es produeixen en el futbol actual. D’igual manera que l’Apòstol aconsellava les comunitats cristianes, podem extrapolar aquest missatge per tal d’aconseguir un esport més pur, on el “fair play” esdevingui un dels elements que el defineixin. En els darrers anys, el futbol ha assolit una dimensió extraordinària, fins al punt que podem afirmar que ha esdevingut un substitut de la religió. El naixement mateix del futbol ens traslladaria a l’àmbit d’allò religiós, perquè quan va aparèixer, durant l’època victoriana anglesa, pedagogs com ara Thomas Arnold van proposar un nou sistema educatiu recuperant aspectes de l’antic mètode clàssic d’educació. Així doncs, les pràctiques esportives (com a element complementari i necessari al curriculum escolar) van tornar a prendre volada després de romandre durant segles a l’oblit. En l’aparició del futbol, remarquem el paper de l’Església anglicana, que (de la mà del cardenal Newton) va potenciar el futbol com a element terapèutic per a la classe obrera industrial i també com a mecanisme d’evangelització. El discurs que abans era propi d’allò sagrat s’ha instal.lat actualment en el món profà, i més concretament en el món del futbol; d’aquesta manera, aspectes com ara la salvació, la resurrecció, els miracles i els precs han entrat a formar part del context esportiu. Considerant tots aquests supòsits, a la present tesi doctoral es realitza un acurat estudi comparatiu dels ritus i dels símbols característics del context religiós cristià i la seva relació amb el món del futbol contemporani. La religió com a fet cultural fa referència a un fet humà complex i específic, un conjunt de sistemes de creences, de pràctiques, de símbols i d’estructures socials, a través de les quals l’ésser humà viu la seva relació amb el món d’allò sagrat. En reemplaçar el fet religiós, el futbol contemporani ha assumit bona part d’aquestes pràctiques en un context profà. / El concepto religioso y el concepto deportivo siempre se había pensado que pertenecían a dos esferas excluyentes de la vida del ser humano, dos conceptos vitales contrapuestos. La vida de la espiritualidad y del alma en contraposición a la concepción más corpórea de la vida. Así pues, el atleta del espíritu y el atleta del cuerpo no podían convivir juntos en el recorrido vital de las personas. La aparición del cristianismo, como una escisión del judaísmo, estuvo fuertemente impregnada de elementos de la cultura clásica helena. Como hilo conductor de la tesis doctoral nos centraremos en el pensamiento de Pablo de Tarso. Cabeza visible de la comunidad cristiana de Antioquia. En sus cartas pastorales utilizó un estilo metafórico impregnado de elementos que provenían de la concepción deportivo-agonística que caracterizó la paideia griega. Un método pedagógico que unía el desarrollo del intelecto con las prácticas físico-deportivas como único camino para alcanzar la virtud. La herencia clásica en el pensamiento del Apóstol en cuanto a su concepción agonística de la vida creemos que puede incidir de manera positiva en el mundo del fútbol formativo. Aspectos como el ascetismo, la negación de los ídolos, la profesión de fe paulina centrada en la existencia de un sólo dios han sido algunos de los elementos que hemos podido comparar con el mundo del fútbol contemporáneo. Las llamadas metáforas deportivas paulinas centraban un discurso donde se apelaba a la lucha, al esfuerzo y a la cooperación que debían de estar presentes en la difícil vida de los primeros cristianos. Atendiendo a estos supuestos en el trabajo doctoral se establecen una serie de principios axiológicos derivados de la esencia del mensaje epistolar de Pablo y que pueden ser utilizados en la mejora de la pedagogía deportiva del fútbol hasta el punto de poder establecer un código ético, que pueda ser útil en el terreno de las escuelas formativas y también como herramienta válida para los educadores de este deporte.Los elementos que caracterizaron el corpus paulinum han sido comparados en el trabajo con rasgos que se producen en el fútbol actual. De la misma manera como el Apóstol aconsejaba a las comunidades cristianas podemos extrapolar dicho mensaje en aras a conseguir un deporte más puro donde el fair play se convierta en uno de los elementos que lo definan. El fútbol, ha alcanzado en los últimos tiempos una dimensión extraordinaria, hasta tal punto, que podemos afirmar que se ha convertido en un sustituto de la religión. El mismo nacimiento de este deporte nos trasladará al ámbito de lo religioso, pues su aparición durante la época victoriana inglesa, donde pedagogos como Thomas Arnold propusieron un nuevo sistema educativo retomando aspectos del antiguo método clásico de educación. Así pues, las prácticas deportivas como un elemento complementario y necesario en el currículo escolar volvieron a alcanzar una gran dimensión después de siglos en el olvido. En este nacimiento del fútbol destacamos el papel relevante de la iglesia anglicana, que de la mano del cardenal Newton potenciaron el fútbol como elemento terapéutico para la deprimida clase obrera industrial y también como un mecanismo de evangelización de la misma. El discurso propio de lo sagrado actualmente se ha instalado en el mundo profano, concretamente en el mundo del futbol, de esta manera aspectos como la salvación, la resurrección, los milagros y los rezos han entrado a formar parte del contexto deportivo. Atendiendo a estos supuestos en la tesis doctoral se hace un minucioso estudio comparativo de los ritos y símbolos característicos del contexto religioso cristiano y su relación con el mundo del fútbol contemporáneo. La religión como hecho cultural se caracteriza por partir del supuesto que el término designa un hecho humano complejo y específico, un conjunto de sistemas de creencias, de prácticas de símbolos y de estructuras sociales a través de las cuales el ser humano vive su relación con el mundo de lo sagrado. El fútbol contemporáneo ha sustituido al hecho religioso. Las prácticas del ser humano actual van dirigidas hacia el mundo de lo profano, hacia el mundo del fútbol. / The religious concept and sporty concept had always thought they belonged to two areas exclusive of human life, two conflicting vital concepts. The life of spirituality and the soul as opposed to the bodily conception of life. Thus the spirit of the athlete and the athlete's body could not live together in the life journey of the people. The emergence of Christianity as a splinter group of Judaism, was strongly imbued with elements of classical Hellenic culture. As the central theme of the doctoral thesis will focus on the thought of Paul of Tarsus. Visible head of the Christian community of Antioch. In his pastoral letters used a metaphorical style imbued with elements coming from the sports-agonistic conception that characterized the Greek paideia. A teaching method that linked the development of the intellect with physical and sports practices as the only way to attain virtue. The classical heritage in the Apostle's thought in terms of agonistic conception of life we can have a positive impact on the world of football training. Aspects such as asceticism, denial of idols, Paul's profession of faith centered on the existence of a single god have been some of the elements we have been able to compare with the world of modern football. Pauline calls focused sports metaphors a speech which appealed to the struggle, effort and cooperation that should be present in the hard life of early Christians. Based on these assumptions in the dissertation establishes a series of axiological principles derived from the essence of the message of Paul and letters that can be used in improving the teaching soccer sports so much to establish an ethical code that can be useful in the field of training schools and also as a valid tool for educators of this sport. The elements that characterized the Pauline corpus have been compared in working with features occurring in football today. In the same way as the Apostle advised the Christian community we can extrapolate the message in order to get a pure sport where fair play to become one of the elements that define it. Football has recently reached an extraordinary dimension to such an extent, we can say that it has become a substitute religion. The very birth of this sport will take us to the realm of religion, since its emergence in Victorian England, where teachers like Thomas Arnold proposed a new education system aspects of the former returning to the classical method of education. So, sports practices as complementary and necessary in the school curriculum again reached a large size after centuries of oblivion. In this birth of football highlight the important role of the Anglican Church, which the hand of Newton boosted Cardinal football as a therapy for the depressed industrial working class and also as a means of evangelization itself. The discourse of the sacred itself has now been installed in the secular world, particularly in the world of football, so things like salvation, resurrection, miracles and prayers have become part of the sporting context. Based on these assumptions in the doctoral thesis is a thorough comparative study of the rites and symbols of Christian religious context and its relationship to the world of contemporary football. Religion as a cultural phenomenon is characterized by the assumption that the term designates a specific complex human fact, a set of belief systems, symbols, practices and social structures through which human beings live their relationship with the sacred world. The contemporary football has replaced the religious fact. The current human practices are directed towards the world of the profane, to the world of football.

Exploring both political aesthetics and the politics of aesthetics to outline an environmental ruralism for art in public spaces, this practice lead research project postulates a “complemental practice”, outlining its methodology and contexts for operation, the rural, spaces of leisure and the public realm. It is a response to threats to spatial and environmental commons from heritage, place-making and nostalgia, psychological inhibition such as a sense of global contingency and widespread economic exploitation. Responses by artists to this situation can be characterised as a binary of dialogism (Kester, 2004) and relational antagonism (Bishop, 2004), i.e. consensual/collaborative or antagonistic/autonomous practices. Informing both is the work of Jacques Rancière who theorises an ethical and social turn in the arts. Through both commissioned and self-initiated projects this thesis offers an interpretation of Jacques Rancière’s conception of dissensus (Rancière, 2010) modulated through an application of the work of philosopher Slajov Žižek on environmental politics and complementarity - the inscription of the universal within the particular (Žižek, 2011). The thesis’ originality lies in this theoretical synthesis which sets out a complemental practice based on dissensus and the undecidability of subject and context, but which dismisses any inflexible schema of either aesthetic autonomy or ethico-political egalitarianism. In addition it suggests an approach to practice in this field and a situation for this - a dissensual infrastructure for the common public realm which is socially relational and evolutionary over time.

<p>The following thesis will focus on understanding the downstream behavioral effects of δORmediated β-arrestinsignaling. δORagonists have been implicated as effective targets for a variety of diseases, however detrimental side effects of opioid-targeting agonists limit their clinical use. δORagonists specifically can induce seizures, however the underlying mechanism contributing to this  behavior  is  unknown.  We  review  this  phenomenon  in  more  detail,  highlighting  current agonists known to induce seizures and potential circuits and pathways involved. Our work suggests β-arrestinsignaling  is  involved,  specifically β-arrestin2  mediated  signaling  may  be  largely contributing  to δORagonist-induced  seizure  behavior.  As  it  is  possible  the β-arrestinisoforms have unique roles in seizure behavior, we also analyzed methods in which to provoke β-arrestinisoform bias of δORtargeting compounds. Though the full mechanism relating δORagonists with seizures remains unknown, our work provides foundational detail of this behavior, implicating the importance of β-arrestinisoform signaling through δOR; allowing for future studies to full define this seizure pathway and develop δORsafer agonists.  </p>

Les opioïdes restent encore à l’heure actuelle les composés pharmacologiques les plus efficaces pour traiter les différentes formes de douleurs, et donc fournir une analgésie thérapeutique. Cependant, l’administration répétée de ces composés entraîne des effets secondaires majeurs comme la dépression respiratoire, la tolérance, mais également, il a été montré que certains de ces opioïdes pouvaient engendrer des états proépileptiques. D’un point de vue thérapeutique, il existe donc un réel besoin pour de nouveaux et meilleurs traitements analgésiques, n’élicitant pas ces effets secondaires. Notre laboratoire étudie la signalétique des récepteurs couplés aux protéines G comme les récepteurs opioïdes et leur capacité de sélectivité fonctionnelle depuis des années, et en particulier celle du récepteur delta opioïde (DOP). En effet, celui-ci présenterait moins d’effets indésirables que le récepteur mu opioïde (MOP) qui est la cible principale des opioïdes classiques comme la morphine. Cependant, il semblerait que le DOP justement soit à l’origine des états proépileptiques précédemment décrits. Ainsi malgré la promesse initiale des agonistes delta par rapport à la diminution des effets secondaires, les effets proépileptiques de certains ont notamment contribué à une baisse d’intérêt vers le DOP et aucun de ses agonistes n’a pu passer les phases de tests cliniques. Cependant, il a été démontré que certains agonistes delta n’entraînaient pas d’effet proépileptique; tandis que d’autres oui. Comment expliquer un tel phénomène ? Ceci est la question que pose la présente recherche. Ainsi notre objectif sera d’obtenir et de comparer les signatures pharmacologiques des agonistes connus pour être proépileptiques versus ceux qui ne le sont pas ; par rapport à la transduction de signal via le récepteur delta opioïde et sa protéine G hétérotrimérique ; et par rapport à un de ses effecteurs principaux pour l’analgésie, un canal potassique rectifiant entrant. Cette comparaison se fera selon les paramètres du modèle classique de la pharmacologie, comme l’efficacité et la puissance ; mais également avec un outil plus récent appelé modèle opérationnel, utilisant des paramètres comme l’affinité et le coefficient de transduction. Pour se faire, le transfert d'énergie par résonance de bioluminescence ou BRET sera utilisé afin de caractériser les différentes voies signalétiques impliquées. Cette recherche s’inscrit dans un vaste contexte de collaboration entre différents laboratoires, et au sein de chacun d’entre eux, dans l’espoir de pouvoir synthétiser un jour, de meilleurs composés pharmacologiques, capables de cibler uniquement les voies médiatrices des effets thérapeutiques voulus, ici l’analgésie ; sans éliciter celles entraînant les effets secondaires associés, ici, les états proconvulsifs. L’aboutissement de cette recherche permettrait donc d’impacter la vie de millions de gens en souffrance, et c’est pourquoi il nous semble plus qu’important de continuer à l’entreprendre. / Opioids are still nowadays the most efficacious pharmacological compounds available to treat the different types of pain, and therefore provide a therapeutic analgesia. However, repeated administration of those compounds lead to major secondary effects like respiratory depression, tolerance, but also it was shown that some opioid compounds could induce seizures. From a therapeutical point of view, there is a serious need for new and better analgesic treatments that do not elicit such adverse effects. Our lab has been studying for years the signaletics of G-protein coupled receptors like the opioid receptors, and their capacity for functional selectivity, especially more recently the one of the delta opioid receptor (DOP). Indeed, this receptor elicits fewer adverse effects compared to the mu opioid receptor (MOP) that is the main target of all clinically used opioids such as morphine. However, it seems like the DOP itself would be responsible for the pro-epileptic states previously described. Thus, despite initial promises of the delta agonists towards reducing adverse effects whilst providing analgesia, the pro-convulsive effects that some seem to elicit have induced a loss of interest towards the DOP, and so far none of its agonists have gone further than pre-clinical trials. However, it has been shown that not all of those DOP agonists had those pro-convulsive adverse effects. How to explain such a phenomenon? This is the question which the present research will be asking. Thus our goal is to obtain and compare pharmacological signatures of the agonists known for being pro-convulsive versus those that are not ; regarding the transduction of signals through the delta opioid receptor and its heterotrimeric G-Protein ; and also regarding one of its main effectors to induce analgesia, an inwardly rectifying potassium channel. This comparison will be done according to the classical parameters of pharmacology, such as efficacy and potency ; but also according to the newest operational model, with parameters such as affinity and transduction coefficients. In order to do so, bioluminescence resonance energy transfer or BRET, will be used in order to characterize and quantify the signalling pathways there implicated. This research is embedded in a vast collaboration context, in between laboratories around the world, and within those laboratories as well, in hope to be able to one day synthesize, better pharmacological compounds, capable of targeting only the pathways responsible for the desired effects, here analgesia ; without triggering the associated adverse effects, here pro-convulsive states. The culmination of this research could allow to impact the lives of millions of people throughout the world, and this is why it is more than important for us to keep on pursuing it.

ABSTRACT Social relationships, habitat utilisation and life history characteristics provide a framework which enables the survival of populations in fluctuating ecological conditions. An understanding of behavioural ecology is critical to the implementation of Natural Resource Management strategies if they are to succeed in their conservation efforts during the emergence of climate change. Egernia whitii from Wedge Island in the Spencer Gulf of South Australia were used as a model system to investigate the interaction of life history traits, scat piling behaviour and chemosensory communication in social lizards. Juveniles typically took ¡Ý 3 years to reach sexual maturity and the results of skeletochronological studies suggested longevity of ¡Ý 13 years. Combined with a mean litter size of 2.2, a pregnancy rate estimated at 75% of eligible females during short-term studies, and highly stable groups, this information suggests several life history features. Prolonged juvenile development and adult longevity may be prerequisite to the development of parental care. Parental care may, in turn, be the determining factor that facilitates the formation of small family groups. In E. whitii parental care takes the form of foetal and neonatal provisioning and tolerance of juveniles by small family or social groups within established resource areas. Presumably, resident juveniles also benefit from adult territorialism. Research on birds suggests that low adult mortality predisposes cooperative breeding or social grouping in birds, and life history traits and ecological factors appear to act together to facilitate cooperative systems. E. whitii practice scat piling both individually and in small groups. Social benefits arising from signalling could confer both cooperative and competitive benefits. Permanent territorial markers have the potential to benefit conspecifics, congenerics and other species. The high incidence of a skink species (E. whitii) refuging with a gecko species (N. milii) on Wedge Island provides an example of interspecific cooperation. The diurnal refuge of the nocturnal gecko is a useful transient shelter for the diurnal skink. Scat piling may release a species ¡®signature¡¯ for each group that allows mutual recognition. Scat piling also facilitates intraspecific scent marking by individual members, which has the potential to indicate relatedness, or social or sexual status within the group. The discovery of cloacal scent marking activity is new to the Egernia genus. E. Whitii differentiate between their own scats, and conspecific and congeneric scats. They scent mark at the site of conspecific scats, and males and females differ in their response to scent cues over time. Scat piling has the potential to make information concerning the social environment available to dispersing transient and potential immigrant conspecifics, enabling settlement choices to be made. This thesis explores some of the behavioural strategies employed by E. whitii to reduce risks to individuals within groups and between groups. Scents eliciting a range of behavioural responses relevant to the formation of adaptive social groupings, reproductive activity, and juvenile protection until maturity and dispersal are likely to be present in this species. Tests confirming chemosensory cues that differentiate sex, kin and age would be an interesting addition to current knowledge. The interaction of delayed maturity, parental care, sociality, chemosensory communication and scat piling highlights the sophistication of this species¡¯ behaviour. An alternative method for permanently marking lizards was developed. Persistence, reliability and individual discrimination were demonstrated using photographic identification and the method was shown to be reliable for broad-scale application by researchers. Naturally occurring toe loss in the field provided a context against which to examine this alternative identification method and revealed the need to further investigate the consequences of routine toe clipping, as this practice appears to diminish survivorship.

This research examines how the practice of curating has been used to further counter-hegemonic agendas in public art institutions since 1989. The central aim is to provide a fuller, contextualised, and medium specific understanding of the how the institutional exhibition might be used to challenge the hegemony of neoliberalism and the post-political consensus politics that sustains its dominance. It provides insights, through both historic case studies and reflective practice, that problematise the idea that the institutional art exhibition is a viable medium for counter-hegemonic critique, or represents the ideal space for the development of an agonistic public discourse. This thesis presents collaborative research undertaken with Tate Liverpool and Liverpool John Moores University. The research presented both extrapolated from, and contributed to, the development of an exhibition, co-curated with Tate Liverpool, entitled Art Turning Left (8 November 2013 – 2 February 2014) and a supplementary publication of the same name. The first section investigates how the idea that curators can counter neoliberal dominance, through institutional exhibition-making, developed. It draws from analyses of previous exhibitions, and the theory of Chantal Mouffe, in order to critically evaluate the curatorial application of counter-hegemonic critique and agonistic practice. It also provides a review of how exhibitions (held in major art institutions since 1989) have articulated politics, in order to determine their relationship to neoliberal dominance, and to identify significant gaps in the dialogue facilitated by these institutions. These analyses provides the theoretical and contextual grounding for the final two chapters, which provide a rationale and critical evaluation of my own attempt to develop an alternative counter-hegemonic curatorial strategy for the exhibition at Tate Liverpool. They document, and analyse, the areas of dissensus, and the ideological and pragmatic limitations that emerged, in trying to realise these theoretical propositions (in practice) in a public art museum. The thesis therefore provides a critical framework for the development of an alternative practice that positions the exhibition as a form of post-political critique and specifically targets the hegemonic role that institutional exhibitions play in reinforcing class distinctions and devaluing nonprofessional creativity.

La leucémie myéloïde aiguë (LMA) est causée par une prolifération anormale de cellules souches sanguines immatures. Notre laboratoire se concentre sur un sous-groupe de la LMA représentant près de 30% de la LAM pédiatrique et caractérisé par la translocation chromosomique KMT2A-MLLT3. L'analyse par séquençage de l’ARN (RNA-seq) dans notre modèle de LMA médiée par la fusion KMT2A-MLLT3 et des échantillons de patients leucémiques a révélé que les gènes codant la chimiokine CCL23 et son récepteur correspondant CCR1 sont surexprimés dans cette maladie. Bien qu'il ait été rapporté que CCL23 et CCR1 sont impliqués dans le trafic de leucocytes et le développement de l'inflammation, les rôles exacts de ces deux protéines dans la leucémogenèse sont inconnus. Pour illustrer les effets de la signalisation CCL23/CCR1 dans la leucémie causée par la fusion KMT2A-MLLT3, nous avons utilisé la technique de transfert d'énergie de résonance de bioluminescence 2 améliorée (ebBRET2) avec des tests d'immuno-empreintes. Nos résultats ont révélé que la signalisation de l'axe CCL23/CCR1 active plusieurs effecteurs de signalisation intermoléculaire, y compris Gi2, G12/13 et β-arrestine 1/2, mais avec un biais vers le recrutement de la β-arrestine. Nous avons également montré que le récepteur CCR1 présente une activité constitutive qui peut se coupler à une voie médiée par la protéine G et activer la voie impliquant les MAP kinases. Enfin, nous avons montré que la signalisation de l'axe CCL23/CCR1 provoque une activation de ERK1/2 dans les lignées cellulaires LMA potentiellement par une voie médiée par la β-arrestine. Ces résultats indiquent que la signalisation de l'axe CCL23/CCR1 active plusieurs voies biologiques pouvant fournir des avantages majeurs pour le développement et la progression de la LMA et présentent ainsi CCL23 et CCR1 comme deux candidats intéressants pour une thérapie ciblée contre la LMA de type KMT2A-MLLT3. / Acute Myeloid Leukemia (AML) is caused by abnormal proliferation of immature blood stem cells. Our lab focuses on an AML subgroup accounting for almost 20% of pediatric AML and characterized by a chromosomal translocation that generates the gene fusion: KMT2A-MLLT3 (KM3). Interestingly, RNA-seq analysis of our KM3 AML model and AML patient samples has revealed that the chemokine CCL23 and its corresponding receptor CCR1 are highly upregulated in this disease. Although it has been reported that CCL23 and CCR1 are implicated in leukocyte trafficking and development of inflammation, the exact roles of these two proteins in leukemia are unknown. To illustrate the effects of CCL23/CCR1 signaling in the KMT2A-MLLT3 rearranged leukemia we employed the enhanced bystander bioluminescence resonance energy transfer 2 (ebBRET2) technique along with phospho-immunoblots assays. Our results revealed that CCL23/CCR1 axis signaling activates multiple intermolecular signaling effectors, including Gi2, G12/13, and β-arrestin1/2 albeit with a bias towards β-arrestin recruitment. We also showed that the CCR1 receptor exhibits a constitutive activity which can couple to a G-protein mediated pathway to activate the MAPK cascade. Finally, we showed that CCL23/CCR1 axis signaling causes an activation of ERK1/2 in AML cell lines potentially through a β-arrestin-mediated pathway. These results indicate that the CCL23/CCR1 axis signaling activates several biological pathways than can provide major advantages for the AML disease development and progression thus presenting both CCL23 and CCR1 as interesting candidates for targeted therapy against KMT2A-MLLT3 AML.