Asymmetry is a universal principle in nature and all sciences. It plays essential roles in living organisms at all biological scales, from homochirality of biomolecules, to cell, tissue, organ, and whole organism development and physiology. Using the Drosophila model, we study the importance of Left-Right (LR) asymmetry at both organismal (brain and visceral laterality) and molecular (homochirality) levels, allowing to develop a ‘holistic’ approach to the question of LR asymmetry generation in a single organism. Brain laterality is a widespread trait in animals, from drosophila to humans, which is manifest at molecular, circuitry and functional level. Despite evidence showing that brain asymmetry is associated to cognitive performance and neurological disorders (e.g., schizophrenia, autism), the contribution of brain asymmetry to the function of the nervous system remains surprisingly overlooked. Particularly, molecular, and genetic determinants of laterality, which are independent from those governing visceral LR asymmetry, remain poorly characterized. In this proposal, we aim at deciphering brain laterality through development of an advanced, novel genetic paradigm using Drosophila as a model system. Building on our recent published and unpublished results, we will develop integrated approaches to study laterality across biological scales. Particularly, using the asymmetric H-neuron model we will perform genome-wide molecular and genetic screens to identify novel factors important for neuronal laterality. Among these, we will study a novel laterality factor leading to a randomization phenotype with situs inversus. Using computational approaches and expression databases, we will expand the repertoire of known asymmetric neuronal circuits and study specific and common mechanisms of laterality establishment. Finally, our recent identification of asymmetric glia paves the way for the study of glia laterality and its interaction with neurons for proper brain function.

In this project we consider the mathematical modeling of a system of many particles interacting with a complex environment. The main difficulty in this situation is that, while the whole system is energy-conservative, the interactions between the particles and the environment through exchanges of energy are expected to give rise to dissipation effects on the particles. Moreover, the presence of many particles causes the medium to react on a given particle depending on how it has been activated by the other particles: this creates a strong coupling between all the particles. The goal of this project is to develop new models and tools for the mathematical modeling of this kind of systems. This project fits in the framework of open systems theory and addresses several challenges in modeling, mathematical analysis and numerical simulation.

Whether public debt can be sustained is a crucial consideration in any macroeconomic analysis of fiscal policy. However, currently, there is no satisfactory criterion for assessing the sustainability of public debt. Existing macroeconomic models on debt sustainability suffer from (a) internal inconsistency because they require nonmodeled social factors to account for the government’s ability to generate a primary fiscal surplus and (b) external inconsistency because they overlook the effects of debt-servicing costs and low-interest rate environments. The SustainDebt project addresses these two inconsistencies in the design of debt sustainability criteria. The first line of research aims to propose more realistic criteria through theoretical modeling based on endogenous growth models. I aim to challenge the prevailing paradigm suggesting that a positive response of the primary fiscal surplus to debt/GDP ratios is sufficient to ensure sustainability. I will explore how governments can secure sustainability when the adjustment of the primary surplus hinges on debt-servicing costs and default risk. I will also develop a micro-foundation that accounts for societal resistance to tax hikes and spending cuts by relying on rent-seeking mechanisms. This model will suggest innovative variables for evaluating debt sustainability, including securing property rights. The second line of research focuses on empirical analyses to reassess knowledge regarding the long-term fiscal policy behavior in Western countries and test theoretical predictions. I will investigate the dynamics of the primary fiscal surplus, considering debt-servicing costs and social/political variables, including political polarization. With insight gained from the designed debt sustainability criteria, I will propose new fiscal rules that can be implemented in the European Union.