
The main objective of this project is to study interactions among phenomena relating to memory and patrimony as they are connected to migrations –taken here in their general understanding of population displacements–, as well as foreign borders, inclusion and exclusion processes and representations on migrants. This work is based on cases of immigration and emigration societies, and integrates specific ones such as colonial and postcolonial societies as well as the ones classified as « collapsed ». Firstly, we aim at understanding, how, to what extent and under which conditions the processes of inclusion and discrimination do (or not) yield actions in the fields of memory and patrimony. Secondly, we intend to analyse repercussions of memory initiatives on the way migration and integration in societies. Working on European cases (FR, GER, SPA, ITL, SLOV, UK, GRE, NDL, POR, AUT) in a comparative perspective with other international cases (ISRL, USA, CA), the present project aims at unfolding complex relations among migration, practices and politics of individual and collective memory-making, national and global history, by using a local, national and transnational approach. The challenge here is to bring forth a cumulative and theoretical reflection on the basis of empirical materials, about how political, social and territorial exclusions related to migrations connect with socio-cultural mediations and appropriations of the past, along a double line: analyzing their potential impacts, and taking them as the consequences of discrimination, as well as the transfer on memory and cultural grounds, of struggles, among which some political ones, to gain recognition. Besides these rallying movements, we also intend to pay attention to memory silences and to absences of specific communities in their national histories which constitute, in addition to other marginalization factors – such as access to labor, living spaces, religious affiliation, etc. – indications of discrimination.
Ligand-induced signal propagation through specific receptors in the plasma membrane is a key process for the cell in order to fulfill its complex role within multicellular organisms. While principal paradigms of how this process is mediated by different receptor types have been established, the molecular and biophysical parameters, which control the specificity of signal activation by the ligand, are far from being clear. A key challenge is to understand the so-called paradox of signaling specificity where a limited set of intracellular signaling effectors can control myriads of signaling outputs. This paradox is particularly well illustrated by the type I interferon receptors (IFNRs) where as many as 13 different IFNs can bind and activate the same IFN? receptor. Complex lateral interactions between integral membrane proteins in the lipid bilayer are believed to play an important role for receptor activation by its ligands. In addition to these interactions at the plasma membrane, increasing evidence shows that the dynamics of endomembranes can play a key role in the selective activation of signaling receptors. The overall aim of this interdisciplinary and collaborative project is to uncover how the specificity of JAK/STAT signaling specificity is controlled by the nano-compartmentalization of the activated IFNR complex at the plasma membrane and in endosomes. IFNRs represent one of the best paradigms to investigate the complexity of these mechanisms since both type I IFNAR (IFN?lpha/?eta? and type II IFNGR (IFN?amma) activate a common STAT1 molecule but display a distinct transcriptional output. P1 has recently shown that IFNR endocytic trafficking and lipid-based nano-organization at the plasma membrane play a key role in the selectivity of JAK/STAT activation by type I and type II IFNs, respectively. P2 has established advanced imaging techniques for monitoring IFNR assembly and spatiotemporal dynamics using single molecule localization imaging techniques. The role of plasma membrane nano-compartmentalization into actin and lipid-based domains will be explored by using biochemical and genetic modifications. Specifically, we aim to identify how specific features of IFNGR localization into lipid rafts, are probably related to specific lipid and galectin interactions. We will identify new interaction partners by mass spectrometry (P1), which will be validated in living cells by functional surface micropatterning (P2). The role of these interaction partners will be further elucidated by biophysical (P2) and functional studies (P1). Based on the detailed mechanistic picture obtained from these studies, we will attempt to systematically swap functional modules between the type I and type II IFN receptors in order to validate their functional relevance in a specific cellular context (P1). The combination of cell biology assays (P1) with biophysics and advanced biophotonics approaches (P2) will give us the unprecedented opportunity to test the provocative hypothesis that the localization and clustering of the activated IFNR complex into distinct membrane nano-compartments (plasma membrane for IFNGR and the early endosome for IFNAR) together with the different spatiotemporal regulation of endosomal IFNR trafficking selectively condition the mechanistics of JAK/STAT activation. The philosophy of our project lies in the emergence of new concepts based on the quantification of biological observables at a single molecule level through the development of innovating experimental and analytical tools. Ultimately, we expect to unravel the molecular basis that conditions the reactivity and the dynamics of the biological macromolecules (IFNRs) and their complexes (JAK/STAT cytosolic partners) when cells are activated by IFNs. Thus, there is an intrinsic link that brings together three different research fields, namely cell biology, in vitro membrane model systems and photonics, at the conceptual and experimental levels.