Circadian oscillation of biological processes has been described in light-sensitive organisms from bacteria to human beings, reflecting the existence of underlying intrinsic clocks. Our recent work suggests that α- and β-cellular clocks are oscillating with distinct phases in vivo and in vitro. These cellular oscillators impact critically on the temporal profiles of insulin and glucagon secretion, and on the transcriptional patterns of key functional genes in the islet cells. Parallel analysis of the molecular properties of α- and β-cell oscillators was conducted by establishing a mouse model expressing three reporters: one diagnostic for α-cells, one specific for β-cells, and third monitoring circadian gene expression. Rodent β-cells have a significant potential for regeneration, suggesting that regenerative therapy for diabetes is feasible. A model for studying β-cell regeneration following 70-80% ablation, proposed and characterized by the Dor’s lab, in combination with the triple reporter mouse strain developed by the Dibner’s lab, represents a unique and powerful tool for characterizing circadian oscillator upon hyperglycemic conditions, and during β-cell regeneration. Crossing these mice to genetic clock-deficient mouse strain will allow unraveling the impact of functional circadian clock on the regenerative capacity of β-cells. In vivo studies in genetic rodent models will be translated to the human model, employing human islet isolated from type 2 diabetic donors, synchronized in vitro. Molecular and functional analysis of the islet cellular clockwork upon type 2 diabetes conditions and during β-cell regeneration will be of high scientific importance and clinical relevance.

Stromatolites represent the oldest forms of life and are commonly defined as laminated organo-sedimentary structures built by the trapping, binding and/or precipitation of minerals via microbial processes. Dead-Sea stromatolites have attracted considerable attention and recently have been used to constrain the late Quaternary lake level curve. This closed-basin contains living and fossil stromatolites at a wide range of water salinity, temperature, oxidation state, and lighting. The basin thus offers a unique opportunity to understand the environmental factors controlling their formation as well as to develop a better chronology for the last glaciation, respectively. We propose to study recent microbial mats (stromatolites) around the Dead-Sea and identify relationships between the environment and observable characteristics that might be recorded in rocks. Based on stromatolites we have mapped around the Dead-Sea, we will combine a geomorphological and geomicrobiological approach to: - Better resolve lake level changes by quantifying the variation of water volumes in the Dead-Sea from the Late Pleistocene to the Holocene - Determine the natural environmental conditions where modern stromatolite types are growing around the Dead-Sea. - Carry out experimental investigations in the laboratory under controlled conditions, from a nanometric- to a mm-scale. By dating these microbialites we will provide a more robust chronology of lake level changes as well as their tempo and magnitude. This is critical for developing predictive patterns of the present day Dead-Sea level changes that are of major societal interest. This is also crucial for unraveling conditions at the "agricultural revolution" incurring around the lake during its last recess.