ERC FUNDED PROJECTS

Obesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes.

1 497 008 €

Start date: 2015-05-01, End date: 2020-04-30

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

As a result of their unplanned, license-free nature, WiFi networks have grown quickly in recent years, giving users unprecedented improvements in wireless access to the Internet. But being “chaotic,” i.e. unplanned, they have grown to be victims of their own success: when eager users set up too many wireless access points in a densely-populated area, the resulting noise and interference hurt everyones throughput and connectivity. Cellular mobile telephone networks are planned carefully, but in order to expand coverage indoors, providers are turning to customer-deployed femtocells, thus incuring the drawbacks of chaotic WiFi networks. We propose a ground-up redesign of chaotic wireless networks, with new architectural contributions focusing on what information the physical layer should pass up to higher layers. We propose a new physical layer interface called SoftAoA that passes angle-of-arrival (AoA) information from the physical layer up to higher layers. Using this expanded physical layer interface, we will first investigate fountain coding and receiver-based rate adaptation methods to improve wireless capacity in the vagaries of the “grey zone” of marginal coverage. Second, we will investigate improvements to security and localization that can be made based on the profiling of incoming packets’ AoA at an access point. Finally, we will investigate how a chaotically-deployed network can mitigate the interference it experiences from networks not under the same administrative control, and manage the interference it causes to those networks. The result will be more scalable, secure, and reliable chaotic wireless networks that play an even more prominent role in our lives.

1 457 675 €

Start date: 2011-11-01, End date: 2016-10-31

COLDNANO (UltraCOLD ion and electron beams for NANOscience), aspires to build novel ion and electron sources with superior performance in terms of brightness, energy spread and minimum achievable spot size. Such monochromatic, spatially focused and well controlled electron and ion beams are expected to open many research possibilities in material sciences, in surface investigations (imaging, lithography) and in semiconductor diagnostics. The proposed project intends to develop sources with the best beam quality ever produced and to assess them in some advanced surface science research domains. Laterally, I will develop expertise exchange with one Small and Medium Enterprise who will exploit industrial prototypes. The novel concept is to create ion and electron sources using advanced laser cooling techniques combined with the particular ionization properties of cold atoms. It would then be first time that “laser cooling” would lead to a real industrial development. A cesium magneto-optical trap will first be used. The atoms will then be excited by lasers and ionized in order to provide the electron source. The specific extraction optics for the electrons will be developed. This source will be compact and portable to be used for several applications such as Low Energy Electron Microscopy, functionalization of semi-conducting surfaces or high resolution Electron Energy Loss Spectrometry by coupling to a Scanning Transmission Electron Microscope. Based on the knowledge developed with the first experiment, a second ambitious xenon dual ion and electron beam machine will then be realized and used to study the scattering of ion and electron at low energy. Finally, I present a very innovative scheme to control the time, position and velocity of individual particles in the beams. Such a machine providing ions or electrons on demand would open the way for the “ultimate” resolution in time and space for surface analysis, lithography, microscopy or implantation.

1 944 000 €

Start date: 2012-02-01, End date: 2017-01-31