Studies on the Hippo Pathway: new insights about a multifaceted signalling

The Hippo pathway is a well-known master regulator of cell growth and proliferation. Many studies have shed light on the centrality of Hippo functions, as this signalling is able to respond to different stimuli and translate them into distinct transcriptional outputs. Therefore, it is clearly implicated in a number of important processes, which alteration has consequences on the correct specification of the single cell, as well as the whole tissue. Even if the core of the signalling has been extensively characterized, it remains unclear which are the “co-workers” that permit the Hippo pathway to answer to so many different stimuli and act as a coordinator of the growth/differentiation balance. Taking advantage of the Drosophila model, which has witnessed most of the discoveries on this signalling pathway, this thesis aims to add some new knowledge about the Hippo pathway molecular mechanisms in different contexts, from development to disease. In the first part I studied the dynamics of the Hippo core kinase protein Warts in the development of the pupal eye. I have found out a critical time point in which the expression and the localization of Warts change suddenly, suggesting the intervention of upstream regulators modulating its activity in an extremely narrow time window. The second goal was investigating the role of the Hippo pathway in the neurodegenerative Gaucher disease. Indeed, I have produced some preliminary results which demonstrate a growth deficit associated with a massive reduction of some Yki targets, supporting a Hyper-Hippo condition underlying this neuropathic syndrome. Finally, I have evaluated the transcription factor Orthodenticle as a co-factor of Yorkie in driving tissue overgrowth, and my findings support a model of interaction of these two molecules based on Yki conformational changes. Altogether, my results lay the foundation for new important studies on the molecular mechanisms ruling Hippo pathway activity.

The right to explanation

This research investigates the use of Artificial Intelligence (AI) systems for profiling and decision-making, and the consequences that it poses to rights and freedoms of individuals. In particular, the research considers that automated decision-making systems (ADMs) are opaque, can be biased, and their logic is correlation-based. For these reasons, ADMs do not take decisions as human beings do. Against this background, the risks for the rights of individuals combined with the demand for transparency of algorithms have created a debate on the need for a new 'right to explanation'. Assuming that, except in cases provided for by law, a decision made by a human does not entitle to a right to explanation, the question has been raised as to whether – if the decision is made by an algorithm – it is necessary to configure a right to explanation for the decision-subject. Therefore, the research addresses a right to explanation of automated decision-making, examining the relation between today’s technology and legal concepts of explanation, reasoning, and transparency. In particular, it focuses on the existence and scope of the right to explanation, considering legal and technical issues surrounding the use of ADMs. The research analyses the use of AI and the problems arising from it from a legal perspective, studying the EU legal framework – especially in the data protection field. In this context, a part of the research is focused on transparency requirements under the GDPR (namely, Articles 13–15, 22, as well as Recital 71). The research aims to outline an interpretative framework of such a right and make recommendations about its development, aiming to provide guidelines for an adequate explanation of automated decisions. Hence, the thesis analyses what an explanation might consist of, and the benefits of explainable AI – examined from legal and technical perspectives.