ERC FUNDED PROJECTS

In the road towards quantum technologies capable of exploiting the revolutionary potential of quantum theory for information technology, a major bottleneck is the large overhead needed to correct errors caused by unwanted noise. Despite important research activity and great progress in designing better error correcting codes and fault-tolerant schemes, the fundamental limits of communication/computation over a quantum noisy medium are far from being understood. In fact, no satisfactory quantum analogue of Shannon’s celebrated noisy coding theorem is known. The objective of this project is to leverage tools from mathematical optimization in order to build an algorithmic theory of optimal information processing that would go beyond the statistical approach pioneered by Shannon. Our goal will be to establish efficient algorithms that determine optimal methods for achieving a given task, rather than only characterizing the best achievable rates in the asymptotic limit in terms of entropic expressions. This approach will address three limitations — that are particularly severe in the quantum context — faced by the statistical approach: the non-additivity of entropic expressions, the asymptotic nature of the theory and the independence assumption. Our aim is to develop efficient algorithms that take as input a description of a noise model and output a near-optimal method for reliable communication under this model. For example, our algorithms will answer: how many logical qubits can be reliably stored using 100 physical qubits that undergo depolarizing noise with parameter 5%? We will also develop generic and efficient decoding algorithms for quantum error correcting codes. These algorithms will have direct applications to the development of quantum technologies. Moreover, we will establish methods to compute the relevant uncertainty of large structured systems and apply them to obtain tight and non-asymptotic security bounds for (quantum) cryptographic protocols.

1 492 733 €

Start date: 2021-01-01, End date: 2025-12-31

"In plants, receptor kinases form the largest family of plasma membrane (PM) receptors and they are involved in virtually all aspects of the plant life, including development, immunity and reproduction. In animals, key molecules that orchestrate the recruitment of signaling proteins to membranes are anionic phospholipids (e.g. phosphatidylinositol phosphate or PIPs). Besides, recent reports in animal and yeast cells suggest the existence of PM nanodomains that are independent of cholesterol and lipid phase and rely on anionic phospholipids as well as electrostatic protein/lipid interactions. Strikingly, we know very little on the role of anionic phospholipids in plant signaling. However, our preliminary data suggest that BKI1, an inhibitory protein of the steroid receptor kinase BRI1, interacts with various PIPs in vitro and is likely targeted to the PM by electrostatic interactions with these anionic lipids. These results open the possibility that BRI1, but also other receptor kinases, might be regulated by anionic phospholipids in plants. Here, we propose to analyze the function of anionic phospholipids in BRI1 signaling, using the root epidermis as a model system. First, we will ask what are the lipids that control membrane surface charge in this tissue and recruit BR-signaling component to the PM. Second, we will probe the presence of PIP-enriched nanodomains at the plant PM using super-resolution microscopy techniques and investigate the roles of these domains in BRI1 signaling. Finally, we will analyze the function of the BKI1-related plant-specific family of anionic phospholipid effectors in plant development. In summary, using a transversal approach ranging from in vitro studies to in vivo validation and whole organism physiology, this work will unravel the interplay between anionic phospholipids and receptor signaling in plants."

1 797 840 €

Start date: 2014-02-01, End date: 2019-01-31

Autophagy is a catabolic pathway that delivers cytoplasmic material to lysosomes for degradation. Under vegetative conditions, the pathway serves as quality control system, specifically targeting damaged or superfluous organelles and protein-aggregates. Cytotoxic stresses and starvation, however, induces the formation of larger autophagosomes that capture cargo unselectively. Autophagosomes are being generated from a cup-shaped precursor membrane, the isolation membrane, which expands to engulf cytoplasmic components. Sealing of this structure gives rise to the double-membrane surrounded autophagosomes. Two interconnected ubiquitin (Ub)-like conjugation systems coordinate the expansion of autophagosomes by conjugating the autophagy related (Atg)-protein Atg8 to the isolation membrane. In an effort to unravel the function of Atg8, we reconstituted the system on model membranes in vitro and found that Atg8 forms together with the Atg12–Atg5-Atg16 complex a membrane scaffold which is required for productive autophagy in yeast. Humans possess seven Atg8-homologs and two mutually exclusive Atg16-variants. Here, we propose to investigate the function of the human Ub-like conjugation system using a fully reconstituted in vitro system. The spatiotemporal organization of recombinant fluorescent-labeled proteins with synthetic model membranes will be investigated using confocal and TIRF-microscopy. Structural information will be obtained by atomic force and electron microscopy. Mechanistic insights, obtained from the in vitro work, will be tested in vivo in cultured human cells. We belief that revealing 1) the function of the human Ub-like conjugation system in autophagy, 2) the functional differences of Atg8-homologs and the two Atg16-variants Atg16L1 and TECPR1 and 3) how Atg16L1 coordinates non-canonical autophagy will provide essential insights into the pathophysiology of cancer, neurodegenerative, and autoimmune diseases.

1 499 726 €

Start date: 2015-04-01, End date: 2021-01-31

Diabetes has become one of the most widespread metabolic disorders with epidemic dimensions affecting almost 6% of the world’s population. Despite modern treatments, the life expectancy of patients with Type 1 diabetes remains reduced as compared to healthy subjects. There is therefore a need for alternative therapies. Towards this aim, using the mouse, we recently demonstrated that the in vivo forced expression of a single factor in pancreatic alpha-cells is sufficient to induce a continuous regeneration of alpha-cells and their subsequent conversion into beta-like cells, such converted cells being capable of reversing the consequences of chemically-induced diabetes in vivo (Collombat et al. Cell, 2009). The PI and his team therefore propose to further decipher the mechanisms involved in this alpha-cell-mediated beta-cell regeneration process and determine whether this approach may be applied to adult animals and whether it would efficiently reverse Type 1 diabetes. Furthermore, a major effort will be made to verify whether our findings could be translated to human. Specifically, we will use a tri-partite approach to address the following issues: (1) Can the in vivo alpha-cell-mediated beta-cell regeneration be induced in adults mice? What would be the genetic determinants involved? (2) Can alpha-cell-mediated beta-cell regeneration reverse diabetes in the NOD Type 1 diabetes mouse model? (3) Can adult human alpha-cells be converted into beta-like cells? Together, these ambitious objectives will most certainly allow us to gain new insight into the mechanisms defining the identity and the reprogramming capabilities of mouse and human endocrine cells and may thereby open new avenues for the treatment of diabetes. Similarly, the determination of the molecular triggers implicated in the beta-cell regeneration observed in our diabetic mice may lead to exciting new findings, including the identification of “drugable” targets of importance for human diabetic patients.

1 500 000 €

Start date: 2012-01-01, End date: 2016-12-31