26 research outputs found

    A comparison between analytical and numerical solution of the Krogh's tissue cylinder model for human bone marrow

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    The Danish physiologist, August Krogh is the founder of the theory of oxygen transport to tissues. It was his famous tissue cylinder model developed for skeletal muscle, together with his colleague mathematician Erlang that laid down the foundation of the mathematical modeling of oxygen transport to tissues. Here an analytical solution of the Krogh’s model has been presented based on justifiable assumptions in order to validate the numerical approach used to solve more realistic oxygen transport models. The numerical solution of Krogh’s model is performed using computational fluid dynamics (CFD) software CFX 4.4. From the analytical solution, it is demonstrated that variation from the numerical result is less than 0.2% which in turn justifies the use of computer software in developing mathematical model for such physiological systems like BM

    Computational design of a biosensor

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    Research poster presented at AACME Summer Bursary Student Poster Competition

    Characterizing the metabolism of Dehalococcoides with a constraint-based model

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    Dehalococcoides strains respire a wide variety of chloro-organic compounds and are important for the bioremediation of toxic, persistent, carcinogenic, and ubiquitous ground water pollutants. In order to better understand metabolism and optimize their application, we have developed a pan-genome-scale metabolic network and constraint-based metabolic model of Dehalococcoides. The pan-genome was constructed from publicly available complete genome sequences of Dehalococcoides sp. strain CBDB1, strain 195, strain BAV1, and strain VS. We found that Dehalococcoides pan-genome consisted of 1118 core genes (shared by all), 457 dispensable genes (shared by some), and 486 unique genes (found in only one genome). The model included 549 metabolic genes that encoded 356 proteins catalyzing 497 gene-associated model reactions. Of these 497 reactions, 477 were associated with core metabolic genes, 18 with dispensable genes, and 2 with unique genes. This study, in addition to analyzing the metabolism of an environmentally important phylogenetic group on a pan-genome scale, provides valuable insights into Dehalococcoides metabolic limitations, low growth yields, and energy conservation. The model also provides a framework to anchor and compare disparate experimental data, as well as to give insights on the physiological impact of "incomplete" pathways, such as the TCA-cycle, CO 2 fixation, and cobalamin biosynthesis pathways. The model, referred to as iAI549, highlights the specialized and highly conserved nature of Dehalococcoides metabolism, and suggests that evolution of Dehalococcoides species is driven by the electron acceptor availability

    Synthetic biology strategies for improving microbial synthesis of "green" biopolymers

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    Polysaccharide-based biopolymers have many material properties relevant to industrial and medical uses, including as drug delivery agents, wound-healing adhesives, and food additives and stabilizers. Traditionally, polysaccharides are obtained from natural sources. Microbial synthesis offers an attractive alternative for sustainable production of tailored biopolymers. Here, we review synthetic biology strategies for select “green” biopolymers: cellulose, alginate, chitin, chitosan, and hyaluronan. Microbial production pathways, opportunities for pathway yield improvements, and advances in microbial engineering of biopolymers in various hosts are discussed. Taken together, microbial engineering has expanded the repertoire of green biological chemistry by increasing the diversity of biobased materials

    Commodity chemicals production in Moorella thermoacetica

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    The thermophilic acetogen Moorella thermoacetica produces acetate from C1 gases during gas fermentation, making it an interesting chassis organism for bio-based chemical production

    Synergistic substrate cofeeding stimulates reductive metabolism

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    Advanced bioproduct synthesis via reductive metabolism requires coordinating carbons, ATP and reducing agents, which are generated with varying efficiencies depending on metabolic pathways. Substrate mixtures with direct access to multiple pathways may optimally satisfy these biosynthetic requirements. However, native regulation favouring preferential use precludes cells from co-metabolizing multiple substrates. Here we explore mixed substrate metabolism and tailor pathway usage to synergistically stimulate carbon reduction. By controlled cofeeding of superior ATP and NADPH generators as ‘dopant’ substrates to cells primarily using inferior substrates, we circumvent catabolite repression and drive synergy in two divergent organisms. Glucose doping in Moorella thermoacetica stimulates CO2 reduction (2.3 g gCDW−1 h−1) into acetate by augmenting ATP synthesis via pyruvate kinase. Gluconate doping in Yarrowia lipolytica accelerates acetate-driven lipogenesis (0.046 g gCDW−1 h−1) by obligatory NADPH synthesis through the pentose cycle. Together, synergistic cofeeding produces CO2-derived lipids with 38% energy yield and demonstrates the potential to convert CO2 into advanced bioproducts. This work advances the systems-level control of metabolic networks and CO2 use, the most pressing and difficult reduction challenge
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