ERC FUNDED PROJECTS

Our field is cryptology. Our overarching objective is to advance significantly the frontiers in design and analysis of high-security cryptography for the future generation. Particularly, we wish to enhance the efficiency, functionality, and, last-but-not-least, fundamental understanding of cryptographic security against very powerful adversaries. Our approach here is to develop completely novel methods by deepening, strengthening and broadening the algebraic foundations of the field. Concretely, our lens builds on the arithmetic codex. This is a general, abstract cryptographic primitive whose basic theory we recently developed and whose asymptotic part, which relies on algebraic geometry, enjoys crucial applications in surprising foundational results on constant communication-rate two-party cryptography. A codex is a linear (error correcting) code that, when endowing its ambient vector space just with coordinate-wise multiplication, can be viewed as simulating, up to some degree, richer arithmetical structures such as finite fields (or products thereof), or generally, finite-dimensional algebras over finite fields. Besides this degree, coordinate-localities for which simulation holds and for which it does not at all are also captured. Our method is based on novel perspectives on codices which significantly widen their scope and strengthen their utility. Particularly, we bring symmetries, computational- and complexity theoretic aspects, and connections with algebraic number theory, -geometry, and -combinatorics into play in novel ways. Our applications range from public-key cryptography to secure multi-party computation. Our proposal is subdivided into 3 interconnected modules: (1) Algebraic- and Number Theoretical Cryptanalysis (2) Construction of Algebraic Crypto Primitives (3) Advanced Theory of Arithmetic Codices

2 447 439 €

Start date: 2017-10-01, End date: 2022-09-30

Asthma exacerbations represent a high unmet medical need in particular in young children. Human Rhinoviruses (HRV) are the main triggers of these exacerbations. Till now Th2 cells were considered the main initiating effector cell type in asthma in general and asthma exacerbations in particular. However, exaggerated Th2 cell activities alone do not explain all aspects of asthma and exacerbations. Building on our recent discovery of type 2 human innate lymphoid cells (ILC2) capable of promptly producing high amounts of IL-5, IL-9 and IL-13 upon activation and on mouse data pointing to an essential role of these cells in asthma and asthma exacerbations, ILC2 may be the main initiating cells in asthma exacerbations in humans. Thus we hypothesize that HRV directly or indirectly stimulate ILC2s to produce cytokines driving the effector functions leading to the end organ effects that characterize this debilitating disease. Targeting ILC2 and HRV in parallel will provide a highly attractive therapeutic option for the treatment of asthma exacerbations. In depth study of the mechanisms of ILC2 differentiation and function will lead to the design effective drugs targeting these cells; thus the first two objectives of this project are: 1) To unravel the lineage relationship of ILC populations and to decipher the signal transduction pathways that regulate the function of ILCs, 2) to test the functions of lung-residing human ILCs and the effects of compounds that affect these functions in mice which harbour a human immune system and human lung epithelium under homeostatic conditions and after infections with respiratory viruses. The third objective of this project is developing reagents that target HRV; to this end we will develop broadly reacting highly neutralizing human monoclonal antibodies that can be used for prophylaxis and therapy of patients at high risk for developing severe asthma exacerbations.

2 499 593 €

Start date: 2014-03-01, End date: 2019-02-28

My objective is to understand the physiologic and medical importance of the posttranslational processing of CAAX proteins (e.g., K-RAS and prelamin A) and to define the suitability of the CAAX protein processing enzymes as therapeutic targets for the treatment of cancer and progeria. CAAX proteins undergo three posttranslational processing steps at a carboxyl-terminal CAAX motif. These processing steps, which are mediated by four different enzymes (FTase, GGTase-I, RCE1, and ICMT), increase the hydrophobicity of the carboxyl terminus of the protein and thereby facilitate interactions with membrane surfaces. Somatic mutations in K-RAS deregulate cell growth and are etiologically involved in the pathogenesis of many forms of cancer. A mutation in prelamin A causes Hutchinson-Gilford progeria syndrome—a pediatric progeroid syndrome associated with misshaped cell nuclei and a host of aging-like disease phenotypes. One strategy to render the mutant K-RAS and prelamin A less harmful is to interfere with their ability to bind to membrane surfaces (e.g., the plasma membrane and the nuclear envelope). This could be accomplished by inhibiting the enzymes that modify the CAAX motif. My Specific Aims are: (1) To define the suitability of the CAAX processing enzymes as therapeutic targets in the treatment of K-RAS-induced lung cancer and leukemia; and (2) To test the hypothesis that inactivation of FTase or ICMT will ameliorate disease phenotypes of progeria. I have developed genetic strategies to produce lung cancer or leukemia in mice by activating an oncogenic K-RAS and simultaneously inactivating different CAAX processing enzymes. I will also inactivate several CAAX processing enzymes in mice with progeria—both before the emergence of phenotypes and after the development of advanced disease phenotypes. These experiments should reveal whether the absence of the different CAAX processing enzymes affects the onset, progression, or regression of cancer and progeria.

1 689 600 €

Start date: 2008-06-01, End date: 2013-05-31

Computer systems today are power limited. As a result, efficiency gains can be translated into performance. Over the past decade we have been so effective at making computation more efficient that we are now at the point where we spend as much energy moving data (from memory to cache to processor) as we do computing the results. And this trend is only becoming worse as we demand more bandwidth for more powerful processors. To improve performance we need to revisit the way we design memory systems from an energy-first perspective, both at the hardware level and by coordinating data movement between hardware and software. CC-MEM will address memory system efficiency by redesigning low-level hardware and high-level hardware/software integration for energy efficiency. The key novelty is in developing a framework for creating efficient memory systems. This framework will enable researchers and designers to compose solutions to different memory system problems (through a shared exchange of metadata) and coordinate them towards high-level system efficiency goals (through a shared policy framework). Central to this framework is a bilateral exchange of metadata and policy between hardware and software components. This novel communication will open new challenges and opportunities for fine-grained optimizations, system-level efficiency metrics, and more effective divisions of responsibility between hardware and software components. CC-MEM will change how researchers and designers approach memory system design from today’s ad hoc development of local solutions to one wherein disparate components can be integrated (composed) and driven (coordinated) by system-level metrics. As a result, we will be able to more intelligently manage data, leading to dramatically lower memory system energy and increased performance, and open new possibilities for hardware and software optimizations.

1 610 000 €

Start date: 2017-03-01, End date: 2022-02-28