The greatest challenge facing our global future today is ‘Health’. To have a better living standard, a growing world population will need easily available and cheaper medicament, especially in metabolic disorder diseases (Cancer, Type-2 diabetes & etc.) and infectious diseases. To combat this impending situation, discovering of novel molecules with unmet physiochemical properties are needed especially in the area of endemic metabolic disorder and infectious diseases. Novel bioactive molecules can be developed by combining basic research with applied science keeping in mind that chemistry is central to everything. This talk will place the scale of the global medical issue in perspective and then discuss some of the issues related to basic science that is needed to emulate drug discovery. With this basic science in place, the design and synthesis of desired compounds and their application to cure diseases through controlling the cell fate in vitro and in vivo will be presented.

Genome interspecific introgressions drive evolution across the animal, plant and fungal kingdoms. We use the model system S. cerevisiae to investigate the birth, evolution and function of interspecies introgressions. Sequencing 1011 S. cerevisiae genomes revealed a ubiquitous gene flow with S. paradoxus. Intorgressions are rare in the highly diverged Asian lineages, consistent with secondary contacts with S. paradoxus occurring mainly after the out-of-China dispersal and promoted by human driven environments.Introgressions initiate from archaic interspecific admixtures, but near-universal hybrid sterility has made their evolution a mystery. We recently discovered a “living fossil” S. cerevisae / S. pardoxus hybrid that reveals a new role for genomic instability at the onset of introgressions. Finally, we use quantitative genetics to measure the fitness landscape of interspecies introgressions across multiple environments

Genomic diversity and composition evolve under diverse and complex constraints such as demography, selection, mutations, or genomic rearrangements. However, the influence of these evolutionary forces and their interactions remain to be fully understood. In that prospect, I will present two projects based on the human genome. First, I will use a population genomics approach and show that purifying selection at linked sites (i.e. background selection) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. Their magnitude are largely determined by variation in recombination rate and base composition and previous reconstruction of human demography based on synonymous sites for instance are thus likely biased by these two mechanisms. However, when focusing on genomic regions with recombination rates above 1.5 cM/Mb and mutation types (C↔G, A↔T), the effects of background selection and gBGC are minimal. I will advocate to use these neutral regions to reconstruct demographies.…

Temporal control over protein phosphorylation and dephosphorylation is crucial for accurate chromosome segregation and forcompletion of the cell division cycle during exit from mitosis.Degradation of mitotic cyclins and activation of Cdk‐counteracting phosphatases lead to protein dephosphorylation. In budding yeast, theCdc14 phosphatase is thought to be a major regulator at this time, while in higher eukaryotes PP2A phosphatases take a dominant role. We usetime-resolved phosphoproteome analysis in budding yeast to evaluate the respective contributions of the kinases and phosphatase input. Thisreveals that successive inactivation of Cdks and of the mitotic kinase Polo contributes to order mitotic exit dephosphorylation events. Cdc14instructs the sequential pattern of phosphorylation changes, in part through its preferential recognition of serine-based cyclin-dependentkinase (Cdk) substrates. PP2ACdc55  in turn exhibit a broad substrate spectrum with some selectivity for phospho-threonines. Our resultsillustrate synergy and coordination between kinases and phosphatases to orchestrate the phosphoproteome by recognising some specific dockingmotifs, phosphoresidus and amino acid regions surrounding the phosphosite.

Endothermic animals (i.e., birds and mammals) produce metabolic heat in their bodies in a way that allows them to maintain a near constant body temperature at values that are typically well above ambient temperature. This is an extravagant economy that requires these animals to maintain elevated energy budgets and spend a large part of their resources on basic maintenance. Several endotherms, however, become ectothermic (torpid) as an adaptive strategy to save energy during periods cold periods. However, the fitness-costs of this strategy could be important, as it entails important threats to organs and tissues due to the toxic effects of ROS production during hypoxia and reperfusion. The small South American marsupial, “monito del monte”  "Dromiciops gliroides", known as the missing link between the American and the Australian marsupials, is one of the few South American mammals known to hibernate. Expressing daily torpor and seasonal hibernation (=”opportunistic hibernation”), this species may provide crucial…

What explains the presence of a gene only in the genome of one species and not in any other? Species-specific protein-coding genes, also known as orphans, can arise "from scratch" from previously non-genic loci, through a process known as de novo gene emergence. How exactly the evolutionary transition from non-gene to functional gene unfolds is unclear. Can such de novo emerging genes increase an organism's fitness, and if so how? Orphan genes can also result from extensive sequence divergence of ancestral genes, which can eventually erase all similarity of a gene to its homologues in other species, a process even less well understood than de novo emergence. I will present novel findings which advance our understanding of both these evolutionary mechanisms and bring us a small step closer to a complete picture of the origins of genetic novelty.