The emergence and evolution of optimistic expectations in schoolchildren

When we study optimism in children, we note the temporary emergence of a bias that leads them to make optimistic predictions. In this study we intend to learn more about changes that can be observed in the optimistic bias of 6- to 12-year old schoolchildren when they predict future events, and in the way they justify those predictions. A total of 77 pupils participated in this study; we evaluated each one of them individually with a Piagetian interview, asking them to formulate predictions about a series of hypothetical situations. After analyzing whether a child's prediction implied that the situation would maintain itself or would change for better or for worse, we classified the justifications they provided for their predictions. Results show that these subjects regarded positive change as more likely in the case of psychological or hybrid events than for purely biological ones, and that younger children tended to display a greater bias in favor of the likelihood of positive change. These younger children justified their predictions stating that nature or the passing of time could be responsible for the changes, without needing further intervention on the part of other agents. Older children, on the other hand, tended to provide similar kinds of explanations to justify their expectation of stasis.

A study of ignorance: suffering and freedom in early Buddhist teachings and parallels in modern neuroscience

What might early Buddhist teachings offer neuroscience and how might neuroscience inform contemporary Buddhism? Both early Buddhist teachings and cognitive neuroscience suggest that the conditioning of our cognitive apparatus and brain plays a role in agency that may be either efficacious or non-efficacious. Both consider internal time to play a central role in the efficacy of agency. Buddhism offers an approach that promises to increase the efficacy of agency. This approach is found in five early Buddhist teachings that are re-interpreted here with a view to explaining how they might be understood as a dynamic basis for ‘participatory will’ in the context of existing free will debates and the neuroscientific work of Patrick Haggard (et al.). These perspectives offer Buddhism and neuroscience a basis for informing each other as the shared themes of: (1) cognition is dynamic and complex/aggregate based, (2) being dynamic, cognition lacks a fixed basis of efficacy, and (3) efficacy of cognition may be achieved by an understanding of the concept of dynamic: as harmony and efficiency and by means of Buddha-warranted processes that involve internal time.

Seasonal variation of acetylcholinesterase, catalase, glutathione s transferase in different size of Pinctada radiata and metal pollution (Pb, Cd, Ni) in Persian Gulf

There are various tools for monitoring the concentration of pollutants on aquatic ecosystems. Today these studies are based on biological monitoring and biomarkers. The aim of this study was to measure the concentration of the acetylcholinesterase (AChE), glutathione S-transferase and catalase as biomarkers of heavy metal contamination in pearl oyster Pinctada radiata and their mechanism in aquatic ecosystems. Heavy metals lead, cadmium and nickel were measured in soft tissue and studied stations in four seasons. Samples were collected seasonally in Lavan stations, Hendurabi and Nakhilo (in the northern Persian Gulf) from spring 2013 to winter of that year by scuba diving. Pearl oysters are divided according to their shells size; shells separated from soft tissues and were transferred to the laboratory for analysis of heavy metals and enzymes. Moopam standard method for were used for measuring the concentration of heavy metals and for analyzing tissue concentrations of glutathione S-transferase in Clam the method recommended by Habig et al in 1974 were used. For measuring acetylcholinesterase Ellman method were used. Catalase contamination in pearl oyster in the supernatant obtained from the study based on the method homogeate soft tissue of mussels (Abei, 1974) was evaluated. The results showed that the concentration of lead has significant difference in sediments station, the concentration of lead in Lavan is significantly higher than the other two stations, This could be due to the movement of tanker, boats and floating refueling and with a considerable amount of wastewater containing oil and Petroleum into the water, and also due to precipitation and industrial discharges the lead in the region is increasing, land-disposed sewage sludge, has large concentrations of lead. Compare the results of this study with standards related and other similar studies at the regional and international level showed that pollutant concentration of heavy metals in all cases significantly less than all the standards and guide values associated. And also compared to other world research results have been far less than others, Being Less of the conclusion given in this research according that nickel is one of the indicators of oil pollution in the study area and emissions have been relatively low of oil. The concentration of acetylcholinesterase at several stations, in large and small sizes and in the seasons had no significant difference. Variations of catalase, and glutathione S-transferase were almost similar to each other and parameters, station and seasons were significantly different in the concentrations of these enzymes. The effects and interaction between various parameters indicate that following parameters has impact on the concentration of catalase and glutathione S-transferase. Stations; Seasonal changes in antioxidant enzymes related to (assuming a constant in salinity and oxygen) to age, reproductive cycle, availability of food and water temperature. With increasing temperature at warm season, antioxidant enzymes were increase, with increasing temperature and abundance of food in the environment the amount of antioxidant enzymes may increase. The presence of the enzyme concentration may indicate that the higher levels of the enzyme to eliminate ROS activities to be any healthier situation. At the time of gonads maturation and spawning season catalase activity increases. This study also indicates that catalase was significantly higher in the warm season. Due to low pollutants of heavy metals in the study area, a lower level of contaminants were observed in shellfish tissue incidents of international standards and strong correlation between the amount of heavy metal contamination in pearl oyster tissue and enzymes was not observed. Therefore, we can say that the pearl oyster remains in a healthy condition and the amount of enzyme is normal.

Toxicity and Contamination in Bear Creek Sediment: Spatial Analysis and Implications for Risk Assessment

The sediments of Bear Creek near Baltimore, Maryland demonstrate substantial toxicity to benthic organisms, and contain a complex mixture of organic and inorganic contaminants. The present study maps the spatial extent and depth profile of toxicity and contamination in Bear Creek, and explores correlations between heavy metals, organic contaminants, and toxic responses. Two novel analytical techniques – handheld XRF and an antibody-based PAH biosensor – were applied to samples from the site to quantify total metals and total PAHs in sediments. By comprehensively assessing toxicity in Bear Creek, the present study provides data to inform future risk assessments and management decisions relating for the site, while demonstrating the benefits of applying joint biological assays and chemical assessment methods to sediments with complex contaminant mixtures.

Effects of gamma and electron-beam irradiation on the individual phenolics of Viola tricolor L. edible flowers.

Edible flowers are being used in culinary preparations to improve the sensorial and nutritional qualities of food, besides improving human health due to the profusion in bioactive compounds [1]. Nevertheless, edible flowers are highly perishable and must be free of insects, which is difficult because they are usually cultivated without using pesticides [2]. Food irradiation is an economically viable technology to extend shelf life of foods, improving their hygiene and quality, while disinfesting insects [3]. The efficiency and safety of radiation processing (using Co-60 or electronaccelerators) have been approved by legal authorities (FDA, USDA, WHO, FAO), as also by the scientific community, based on extensive research [4]. Viola tricolor L. (heartseases), from Violaceae family, is one of the most popular edible flowers. Apart from being used as food, it has also been applied for its medicinal properties, mainly due to their biological activity and phenolic composition [5]. Herein, the phenolic compounds were analyzed by HPLC-DAD-ESI/MS and linear discriminant analysis (LDA) was performed to compare the results from flowers submitted to different irradiation doses and technologies (Co-60 and electron-beam). Quercetin-3-O-(6-O-rhamnosylglucoside)-7-O-rhamnoside (Figure 1) was the most abundant compound, followed by quercetin-3-O-rutinoside and acetyl-quercetin-3-O (6-O-rhamnosylglucoside)-7-O-rhamnoside. In general, irradiated samples (mostly with 1 kGy) showed the highest phenolic compounds content. The LDA outcomes indicated that differences among phenolic compounds effectively discriminate the assayed doses and technologies, defining which variables contributed mostly to that separation. This information might be useful to define which dose and/or technology optimizes the content in a specific phenolic compound. Overall, irradiation did not negatively affect the levels of phenolic compounds, providing the possibility of its application to expand the shelf life of V. tricolor and highlighting new commercial solutions for this functional food.

Seaweed Aquaculture and Marine Biotechnology

Macroscopic marine algae, typically known as macroalgae or seaweeds, form an important living resource of the oceans, as primary producers. People have collected seaweeds for food, both for humans and animals for millennia. They also have been a source of nutrient rich fertilizers, as well as a source of gelling agents known as phycocolloids. More recently macroalgae are playing significant roles in medicine and biotechnology. Although Biotechnology and in particular marine biotechnology may have different meanings for different people, under the present context we will consider a broader definition. Marine biotechnology consists on the use of biological knowledge and/or the application of biological techniques on marine organisms, for the development of products in some way beneficial for humans. Seaweed aquaculture is, therefore a biotechnology activity. It is also one that can allow for further development of the industry. Today, seaweed cultivation techniques are standardized, routine and economical. Several factors, including understanding the environmental regulation of life histories and asexual propagation of thalli, are responsible for the success of large-scale seaweed cultivation. Presently, seaweed aquaculture represents approximately 23% of the world’s aquaculture production, including fish, crustaceans and other animals. A promising approach for the development of seaweed aquaculture, and aquaculture in general, is the integrated multi-trophic aquaculture (IMTA). In these systems, fed-aquaculture is combined with extractive organisms like bivalves and/or algae. The constraints and advantages of IMTA will be discussed. In particular, land based IMTA systems allow for much greater environmental and input controls. Traceability, security of supply, high-quality standards and safety should be the future of seaweed aquaculture and contribute for the development of marine biotechnology.

Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

The interaction of 4-nerolidylcatechol (4-NRC), a potent antioxidant agent, and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated by the solubility method using Fourier transform infrared (FTIR) methods in addition to UV-Vis, (1)H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The inclusion complexes were prepared using grinding, kneading and freeze-drying methods. According to phase solubility studies in water a B(S)-type diagram was found, displaying a stoichiometry complexation of 2:1 (drug:host) and stability constant of 6494 +/- A 837 M(-1). Stoichiometry was established by the UV spectrophotometer using Job's plot method and, also confirmed by molecular modeling. Data from (1)H-NMR, and FTIR, experiments also provided formation evidence of an inclusion complex between 4-NRC and HP-beta-CD. 4-NRC complexation indeed led to higher drug solubility and stability which could probably be useful to improve its biological properties and make it available to oral administration and topical formulations.

PHYSICAL FACTORS IN B CELL ACTIN DYNAMICS AND ACTIVATION

Cells adapt to their changing world by sensing environmental cues and responding appropriately. This is made possible by complex cascades of biochemical signals that originate at the cell membrane. In the last decade it has become apparent that the origin of these signals can also arise from physical cues in the environment. Our motivation is to investigate the role of physical factors in the cellular response of the B lymphocyte. B cells patrol the body for signs of invading pathogens in the form of antigen on the surface of antigen presenting cells. Binding of antigen with surface proteins initiates biochemical signaling essential to the immune response. Once contact is made, the B cell spreads on the surface of the antigen presenting cell in order to gather as much antigen as possible. The physical mechanisms that govern this process are unexplored. In this research, we examine the role of the physical parameters of antigen mobility and cell surface topography on B cell spreading and activation. Both physical parameters are biologically relevant as immunogens for vaccine design, which can provide laterally mobile and immobile antigens and topographical surfaces. Another physical parameter that influences B cell response and the formation of the cell-cell junction is surface topography. This is biologically relevant as antigen presenting cells have highly convoluted membranes, resulting in variable topography. We found that B cell activation required the formation of antigen-receptor clusters and their translocation within the attachment plane. We showed that cells which failed to achieve these mobile clusters due to prohibited ligand mobility were much less activation competent. To investigate the effect of topography, we use nano- and micro-patterned substrates, on which B cells were allowed to spread and become activated. We found that B cell spreading, actin dynamics, B cell receptor distribution and calcium signaling are dependent on the topographical patterning of the substrate. A quantitative understanding of cellular response to physical parameters is essential to uncover the fundamental mechanisms that drive B cell activation. The results of this research are highly applicable to the field of vaccine development and therapies for autoimmune diseases. Our studies of the physical aspects of lymphocyte activation will reveal the role these factors play in immunity, thus enabling their optimization for biological function and potentially enabling the production of more effective vaccines.

The scientific rationale, design and implementation plan for a Biogeochemical-Argo float array

Biogeochemical-Argo is the extension of the Argo array of profiling floats to include floats that are equipped with biogeochemical sensors for pH, oxygen, nitrate, chlorophyll, suspended particles, and downwelling irradiance. Argo is a highly regarded, international program that measures the changing ocean temperature (heat content) and salinity with profiling floats distributed throughout the ocean. Newly developed sensors now allow profiling floats to also observe biogeochemical properties with sufficient accuracy for climate studies. This extension of Argo will enable an observing system that can determine the seasonal to decadal-scale variability in biological productivity, the supply of essential plant nutrients from deep-waters to the sunlit surface layer, ocean acidification, hypoxia, and ocean uptake of CO2. Biogeochemical-Argo will drive a transformative shift in our ability to observe and predict the effects of climate change on ocean metabolism, carbon uptake, and living marine resource management. Presently, vast areas of the open ocean are sampled only once per decade or less, with sampling occurring mainly in summer. Our ability to detect changes in biogeochemical processes that may occur due to the warming and acidification driven by increasing atmospheric CO2, as well as by natural climate variability, is greatly hindered by this undersampling. In close synergy with satellite systems (which are effective at detecting global patterns for a few biogeochemical parameters, but only very close to the sea surface and in the absence of clouds), a global array of biogeochemical sensors would revolutionize our understanding of ocean carbon uptake, productivity, and deoxygenation. The array would reveal the biological, chemical, and physical events that control these processes. Such a system would enable a new generation of global ocean prediction systems in support of carbon cycling, acidification, hypoxia and harmful algal blooms studies, as well as the management of living marine resources. In order to prepare for a global Biogeochemical-Argo array, several prototype profiling float arrays have been developed at the regional scale by various countries and are now operating. Examples include regional arrays in the Southern Ocean (SOCCOM ), the North Atlantic Sub-polar Gyre (remOcean ), the Mediterranean Sea (NAOS ), the Kuroshio region of the North Pacific (INBOX ), and the Indian Ocean (IOBioArgo ). For example, the SOCCOM program is deploying 200 profiling floats with biogeochemical sensors throughout the Southern Ocean, including areas covered seasonally with ice. The resulting data, which are publically available in real time, are being linked with computer models to better understand the role of the Southern Ocean in influencing CO2 uptake, biological productivity, and nutrient supply to distant regions of the world ocean. The success of these regional projects has motivated a planning meeting to discuss the requirements for and applications of a global-scale Biogeochemical-Argo program. The meeting was held 11-13 January 2016 in Villefranche-sur-Mer, France with attendees from eight nations now deploying Argo floats with biogeochemical sensors present to discuss this topic. In preparation, computer simulations and a variety of analyses were conducted to assess the resources required for the transition to a global-scale array. Based on these analyses and simulations, it was concluded that an array of about 1000 biogeochemical profiling floats would provide the needed resolution to greatly improve our understanding of biogeochemical processes and to enable significant improvement in ecosystem models. With an endurance of four years for a Biogeochemical-Argo float, this system would require the procurement and deployment of 250 new floats per year to maintain a 1000 float array. The lifetime cost for a Biogeochemical-Argo float, including capital expense, calibration, data management, and data transmission, is about $100,000. A global Biogeochemical-Argo system would thus cost about $25,000,000 annually. In the present Argo paradigm, the US provides half of the profiling floats in the array, while the EU, Austral/Asia, and Canada share most the remaining half. If this approach is adopted, the US cost for the Biogeochemical-Argo system would be ~$12,500,000 annually and ~$6,250,000 each for the EU, and Austral/Asia and Canada. This includes no direct costs for ship time and presumes that float deployments can be carried out from future research cruises of opportunity, including, for example, the international GO-SHIP program (http://www.go-ship.org). The full-scale implementation of a global Biogeochemical-Argo system with 1000 floats is feasible within a decade. The successful, ongoing pilot projects have provided the foundation and start for such a system.

Environmental and grazing influence on spatial variability of intertidal biofilm on subtropical rocky shores

Epilithic biofilm on rocky shores is regulated by physico-chemical and biological factors and is important as a source of food for benthic organisms. The influences of environmental and grazing pressure on spatial variability of biomass of biofilm were evaluated on shores on the north coast of São Paulo State (SE Brazil). A general trend of greater abundance of microalgae was observed lower on the shore, but neither of the environmental factors evaluated (wave exposure and shore level) showed consistent effects, and differences were found among specific shores or times (September 2007 and March 2008). The abundance of slow-moving grazers (limpets and littorinids) showed a negative correlation with chlorophyll a concentration on shores. However, experimental exclusion of these grazers failed to show consistent results at small spatial scales. Observations of divergent abundances of the isopod Ligia exotica and biomass of biofilm on isolated boulders on shores led to a short exclusion experiment, where the grazing pressure by L. exotica significantly decreased microalgal biomass. The result suggests that grazing activities of this fast-moving consumer probably mask the influence of slow-moving grazers at small spatial scales, while both have an additive effect at larger scales that masks environmental influences. This is the first evaluation of the impact of the fast-moving herbivore L. exotica on microalgal biomass on rocky shores and opens an interesting discussion about the role of these organisms in subtropical coastal environments.

Metastability and dynamics of stem cells: from direct observations to inference at the single cell level

Organismal development, homeostasis, and pathology are rooted in inherently probabilistic events. From gene expression to cellular differentiation, rates and likelihoods shape the form and function of biology. Processes ranging from growth to cancer homeostasis to reprogramming of stem cells all require transitions between distinct phenotypic states, and these occur at defined rates. Therefore, measuring the fidelity and dynamics with which such transitions occur is central to understanding natural biological phenomena and is critical for therapeutic interventions.

While these processes may produce robust population-level behaviors, decisions are made by individual cells. In certain circumstances, these minuscule computing units effectively roll dice to determine their fate. And while the 'omics' era has provided vast amounts of data on what these populations are doing en masse, the behaviors of the underlying units of these processes get washed out in averages.

Therefore, in order to understand the behavior of a sample of cells, it is critical to reveal how its underlying components, or mixture of cells in distinct states, each contribute to the overall phenotype. As such, we must first define what states exist in the population, determine what controls the stability of these states, and measure in high dimensionality the dynamics with which these cells transition between states.

To address a specific example of this general problem, we investigate the heterogeneity and dynamics of mouse embryonic stem cells (mESCs). While a number of reports have identified particular genes in ES cells that switch between 'high' and 'low' metastable expression states in culture, it remains unclear how levels of many of these regulators combine to form states in transcriptional space. Using a method called single molecule mRNA fluorescent in situ hybridization (smFISH), we quantitatively measure and fit distributions of core pluripotency regulators in single cells, identifying a wide range of variabilities between genes, but each explained by a simple model of bursty transcription. From this data, we also observed that strongly bimodal genes appear to be co-expressed, effectively limiting the occupancy of transcriptional space to two primary states across genes studied here. However, these states also appear punctuated by the conditional expression of the most highly variable genes, potentially defining smaller substates of pluripotency.

Having defined the transcriptional states, we next asked what might control their stability or persistence. Surprisingly, we found that DNA methylation, a mark normally associated with irreversible developmental progression, was itself differentially regulated between these two primary states. Furthermore, both acute or chronic inhibition of DNA methyltransferase activity led to reduced heterogeneity among the population, suggesting that metastability can be modulated by this strong epigenetic mark.

Finally, because understanding the dynamics of state transitions is fundamental to a variety of biological problems, we sought to develop a high-throughput method for the identification of cellular trajectories without the need for cell-line engineering. We achieved this by combining cell-lineage information gathered from time-lapse microscopy with endpoint smFISH for measurements of final expression states. Applying a simple mathematical framework to these lineage-tree associated expression states enables the inference of dynamic transitions. We apply our novel approach in order to infer temporal sequences of events, quantitative switching rates, and network topology among a set of ESC states.

Taken together, we identify distinct expression states in ES cells, gain fundamental insight into how a strong epigenetic modifier enforces the stability of these states, and develop and apply a new method for the identification of cellular trajectories using scalable in situ readouts of cellular state.

Harmonised framework for ecological risk assessment of sediments from ports and estuarine zones of North and South Atlantic

This paper presents a harmonised framework of sediment quality assessment and dredging material characterisation for estuaries and port zones of North and South Atlantic. This framework, based on the weight-of-evidence approach, provides a structure and a process for conducting sediment/dredging material assessment that leads to a decision. The main structure consists of step 1 (examination of available data); step 2 (chemical characterisation and toxicity assessment); decision 1 (any chemical level higher than reference values? are sediments toxic?); step 3 (assessment of benthic community structure); step 4 (integration of the results); decision 2 (are sediments toxic or benthic community impaired?); step 5 (construction of the decision matrix) and decision 3 (is there environmental risk?). The sequence of assessments may be interrupted when the information obtained is judged to be sufficient for a correct characterisation of the risk posed by the sediments/dredging material. This framework brought novel features compared to other sediment/dredging material risk assessment frameworks: data integration through multivariate analysis allows the identification of which samples are toxic and/or related to impaired benthic communities; it also discriminates the chemicals responsible for negative biological effects; and the framework dispenses the use of a reference area. We demonstrated the successful application of this framework in different port and estuarine zones of the North (Gulf of Cadiz) and South Atlantic (Santos and Paranagua Estuarine Systems).

Cortisol Reactivity and Observed Parenting among Mothers of Children with and without ADHD

Parenting is a robust predictor of developmental outcomes among children with ADHD. Early parenting predicts the persistence and course of ADHD and comorbid problems above and beyond risk associated with shared genetic effects. Yet, on average, mothers of children with ADHD are less positive and more negative in their parent-child interactions compared to mothers of non-disordered children. Little is known about psychobiological markers which may be associated with individual variations in maternal parenting in families of children with ADHD. Neurobiological models of parenting suggest that maternal cortisol levels following a stressor may be positively associated with hostile and intrusive parenting; however, to date no studies have examined maternal cortisol reactivity and parenting in school-age, or clinical samples of, children. Mothers’ regulation of physiological stress responses may be particularly important for families of children with ADHD, as parenting a child with chronically challenging behaviors represents a persistent environmental stressor. The current study sought to extend the existing literature by providing an empirical examination of the relationship between maternal cortisol reactivity following two laboratory stressors and parenting among mothers of children with and without ADHD. It was hypothesized that child ADHD group would moderate the relationship between cortisol reactivity and self-reported and observed parenting. Greater total cortisol output and greater increase in cortisol during the TSST were associated with decreased positive parenting and increased negative and directive parenting, with the exception of parental involvement, which was associated with increased cortisol output during the TSST. Conversely, cortisol output during the PCI was associated with increased positive parenting, increased parental involvement, and decreased negative parenting. In contrast to the TSST, a greater decrease in cortisol during the PCI indicated more positive parenting and parental involvement. These associations were specific to mothers of children with ADHD, with the exception of maternal directiveness, which was specific to comparison mothers. Findings add to our understanding of physiological processes associated with maternal parenting and contribute to an integrative biological, psychological, and cognitive process model of parenting in families of children with ADHD.

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.