Perspective taking, the ability to take another person's perspective, is instrumental in building successful and harmonious partnerships, from romantic relationships to international cooperation. Yet, failure to achieve perspective taking, or egocentrism, is increasingly observed in clinical and healthy populations. Fortunately, perspective taking is a skill that can be acquired through training, but, to date, existing training has only yielded limited results. This project aims to conduct the first epidemiological study of egocentrism (i.e. to assess its prevalence in Europe, its severity, its psycho-sociological determinants, and its consequences on mental health and well-being) and the first large-scale perspective-taking training intervention for both healthy and clinical populations. By distinguishing the profiles of egocentrism and identifying their key determinants, Work Package (WP) 1 will assess perspective-taking performance (and associated psycho-sociological factors) in Alzheimer, addictive disorder, anorexic, and forensic patients and in matched healthy control participantss. Building on the Supervisor’s team expertise in devising and conducting training interventions, WP2 will devise and conduct intervention programs tailored to the distinct egocentrism profiles in the same populations as WP1. WP3 will export the WP1-WP2 methodology into a free web-based assessment and training tool to conduct the epidemiological study and the large-scale training intervention in the general population, from adolescents to seniors. The assessment and training tool will be made available to all clinicians, researchers and all other actors to foster further uses such as for youth education programs, support programs for caregivers, or mental health promotion programs targeting vulnerable populations.

## Project outline: Ground-breaking rethinking of the user-computer relationship We aim to develop an ERC Synergy Grant project that will redefine the relation between the user and computer program, grounding it in a historically-anchored broad notion of literacy. Leveraging this foundational rethinking of computer literacy, we develop a new framework centered on the novel concept of Literate User Interface (LUI). The integration of historical and epistemological research methods into fields that are usually future-oriented is a basic methodological innovation of our proposal. It enables us to provide a realistic vision for the future which (i) is based on a deeper understanding of the current situation and the social and technical forces shaping it, (ii) makes it possible to uncover original conceptualizations and techniques from past movements which have been forgotten or which have been reshaped historically to become unrecognizable and (iii) provides an understanding of why visions on the future from the past failed to materialize. ## Research objective I: The concept of a Literate User Interface (LUI) We will (i) develop the concept of Literate User Interface (LUI) as a basic new approach for building systems that can be understood and controlled by their users, focusing on the level of the (socio-technical) system rather than on a particular programming language; (ii) implement concrete materializations of the concept showing its viability and (iii) use human-centric research methods to build systems that enable the user to steadily reconceptualize their relation to programs. ## Research objective II: New approach to computer education We use a transdisciplinary research method to establish a broad notion of computer literacy. We will (i) integrate historical perspective into education in order to provide accessible broad perspective, (ii) precisely characterize a broad notion of literacy, shifting from small-scale coding towards broad-scale understanding of systems and their consequences and (iii) develop specific educational materials based on systems that implement our notion of Literate User Interface to show that such broad notion can lead to a deep understanding of realistic complex computer systems. ## Transdisciplinary collaborative methodology The only feasible approach for realizing these objectives is through a transdisicplinary method bringing together four main areas of research: (i) computer science education, (ii) history and philosophy of computing, (iii) foundations of computer programming, and (iv) human-centric interface design. Our current proposal goes beyond narrow disciplinary approaches within history, philosophy, education and computer science. It brings those fields together and places them on equal footing to work on one and the same problem: how to solve the literacy crisis? Due to its transdisciplinary nature, a ground-breaking ERC Synergy Grant project proposal can only be developed in a close collaboration with academic and industry experts across multiple disciplines. The requested funding will make it possible to organize the necessary series of workshops and research meetings, leading to an ERC Synergy Grant proposal submitted in autumn 2025.

The role of chronic inflammation in obesity, metabolic and cardiovascular diseases is increasingly recognized. Bile acids (BA), synthesized in the liver and modified by the gut flora, facilitate lipid absorption in the intestine. BA modulate lipid and glucose homeostasis by activating the nuclear receptor FXR and the GPCR TGR5. Intriguingly, peripheral BA concentrations are elevated in type 2 diabetes (T2D) and FXR mediates the beneficial metabolic response to gastric bypass in mice. The immune system plays an important role in the cross-talk with metabolic tissues, such as liver, intestine and adipose tissues. However, whether BA modulate immune cell function is unknown. Our unpublished results identifying FXR and TGR5 expression in lymphoid cells, prompt us to study their role in the regulation of glucose and lipid metabolism through immune cell modulation. Using reporter mice and specific ligands, we will characterize the immune cells expressing active FXR and TGR5. We will determine their role in metabolism and inflammation by immune cell-specific gene inactivation in models of obesity, T2D and elevated peripheral blood BA concentrations. Mass cytometry, cell sorting and single cell transcriptomic analysis will allow the identification of gene networks regulated by BA and their receptors. As microbiota generate biologically active secondary BA, we will assess the impact of microbiota depletion and subsequent BA acid pool modifications on immune cell populations. Translational studies in humans with altered BA metabolism and pharmacological treatment with anti-diabetic BA sequestrants will allow assessment of alterations in immune functions. This project aims to identify an hitherto unexplored role of BA through modulation of the immune system on T2D, NAFLD and dyslipidemia. Success of the project critically depends on an integrative approach uniquely undertaken in my laboratory through its unique multidisciplinary expertise in basic and translational biology.

The escalating epidemic of obesity, type-2 diabetes and metabolic syndrome represents one of the most pressing and costly biomedical challenges confronting modern society. The impaired action of peripheral hormones on brain circuits controlling feeding and energy homeostasis, also known as "central hormone resistance", is increasingly recognized as playing a role in the pathophysiology of these disorders. The host laboratory has raised the groundbreaking notion that tanycytes, a specific type of hypothalamic glial cells, act as "gatekeepers" that regulate the access of blood-borne signals to the hypothalamus, and in particular, their vesicular transport into the cerebrospinal fluid, from where they enters other metabolic-hormone-sensitive regions. The overall objective of this proposal is to further develop this highly original angle by using state-of-the-art approaches to i) gain new insights into the molecular mechanisms underlying structural changes in the tanycytic barrier in response to fluctuating concentrations of circulating glucose, and determine how these processes are altered in animal models with acquired type-2 diabetes, and ii) explore the possibility that tanycytes are involved in the shuttling of circulating glucose into the cerebrospinal fluid (CSF) and that the tanycytic expression of the NMDA receptor plays a role in this process. This research promises to shed new light on the molecular mechanisms used by the hypothalamus to integrate key peripheral signals and coordinate energy homeostasis. The results will pave the way for the development of new treatment strategies to overcome hormone resistance in human obesity and associated metabolic syndromes.