1,801 research outputs found
Using synthetic biology to make cells tomorrow's test tubes
The main tenet of physical biology is that biological phenomena can be subject to the same quantitative and predictive understanding that physics has afforded in the context of inanimate matter. However, the inherent complexity of many of these biological processes often leads to the derivation of complex theoretical descriptions containing a plethora of unknown parameters. Such complex descriptions pose a conceptual challenge to the establishment of a solid basis for predictive biology. In this article, we present various exciting examples of how synthetic biology can be used to simplify biological systems and distill these phenomena down to their essential features as a means to enable their theoretical description. Here, synthetic biology goes beyond previous efforts to engineer nature and becomes a tool to bend nature to understand it. We discuss various recent and classic experiments featuring applications of this synthetic approach to the elucidation of problems ranging from bacteriophage infection, to transcriptional regulation in bacteria and in developing embryos, to evolution. In all of these examples, synthetic biology provides the opportunity to turn cells into the equivalent of a test tube, where biological phenomena can be reconstituted and our theoretical understanding put to test with the same ease that these same phenomena can be studied in the in vitro setting
Multiscale Modelling of Malaria-Infected Red Blood Cells
Red blood cells (RBCs) are the type of human cells that are most accessible to biophysical multiscale modelling because they feature a regular molecular cell envelope organization and lack internal organelles. Extensive previous research on how their physical properties are shaped by the actin-spectrin network and other molecular constituents provides a good basis to understand the physical consequences of becoming infected by malaria parasites, which use RBCs to hide from the immune system. After invasion, the malaria parasite rebuilds the RBC-envelope, relying on the self-assembly of parasite proteins released into the cytoplasm. Optical tweezer experiments have shown that infected RBCs (iRBCs) become stiffer. Here, the underlying mechanisms are investigated by quantitative analysis of the flickering spectrum of iRBCs. Extending the membrane Hamiltonian by anchoring points, we find that the parasite stiffens the membrane mostly by introducing more connections between the lipid bilayer and the underlying cytoskeleton. To identify the exact points of attack in the RBC-cytoskeleton,
a reaction-diffusion model is developed to investigate the dynamical equilibrium of the RBC-cytoskeleton, allowing us to simulate different scenarios of parasite protein
self-assembly and to compare these results with experimental data. The parasite induces protrusions to make the iRBC adhesive, thus increasing residence time in the vasculature and avoiding clearance by the spleen. The number of new transmembrane receptors incorporated into the cell membrane is estimated by quantitative analysis of fluorescence and electron microscopy data. We develop a finite element model aiming to predict the effect of these changes on the movement of iRBCs in hydrodynamic flow. Finally, as an instructive contrast to RBC-mechanics, we
investigate the spreading of tissue cells onto micropatterned substrates leading to a complete change in their actin cytoskeleton. A Cellular Potts Model is used to describe this highly dynamic situation. We find that due to its focus on geometrical aspects, it predicts reliably how a family of actin stress fibres is formed, which serves as memory of the spreading process
Composition models for augmented instruments: HASGS as case study
This paper presents the concept of HASGS regarding the
augmentation procedures applied to an acoustic instrument, at the
same time that it is analyzed how composers applied technology
prototyped to the composition of works. The development of
HASGS has been driven by the compositional aspects of the original
music created for this specific electronic augmented instrumental
system. Instruments are characterized not only by their sound
and acoustical properties but also by their performative
interface and evolutionary repertoire. This last aspect has the
potential to establish a practice among performers at the same
time as creating the ideal of community contributing to the past,
present and future of that instrument. Augmenting an acoustic
instrument places some limitations on the designer ́s palette of
feasible gestures because of those intrinsic performance
gestures, and the existing mechanical interface, which have
been developed over years, sometimes, centuries of acoustic
practice. We conclude that acoustic instruments and digital
technology, are able to influence and interact mutually creating
Augmented Musical Performance environments based on the
aesthetics of the repertoire being developed. This work is, as
well, a resource of compositional methods to composers and
programmers.publishe
Identification of Virulence Factors in Nematode-Trapping Fungi - Insights from Genomics, Transcriptomics and Proteomics
Nematode-trapping fungi are soil-living organisms with the unique ability to capture and infect free-living nematodes. The interest in studying these fungi arises from their potential use as biological control agents for plant- and animal-parasitic nematodes. To enter the parasitic stage, nematode-trapping fungi develop different kinds of trapping structures. In order to understand more about the evolution of parasitism in the nematode-trapping fungi and to identify virulence factors in these fungi genomic, transcriptomic and proteomic studies were conducted. First, the genome of Monacrosporium haptotylum was sequenced and compared to the genome of the closely related Arthrobotrys oligospora and also to genomes of other ascomycetes. Two genomic mechanisms were identified that likely have been important for the adaptation to parasitism in these two nematode-trapping fungi. Firstly, the expansion of certain protein-domain families and a large number of species-specific genes indicated that gene duplications followed by functional diversification have played a major role in the evolution of the nematode-trapping fungi. Gene expression analyses indicated that many of these genes are important for pathogenicity. Secondly, comparisons of gene expression of orthologs between the two fungi during infection indicated that differential regulation was an important mechanism for the evolution of parasitism in nematode-trapping fungi. Second, the proteome of the trapping structure in M. haptotylum was characterized using mass spectrometry. The trapping structure in this fungus is called knob and is a single cell that can be separated from the vegetative mycelia. The results showed that there was a large difference in the protein content of the knob and that of the mycelium. The knob proteome was overrepresented in secreted proteins, including small secreted proteins, peptidases and proteins containing the carbohydrate-binding domain WSC. Transcripts encoding such proteins were also highly upregulated in M. haptotylum during infection. We suggest that the knob contains many of the proteins needed in the early stages of infection. Finally, to gain further insight about what genes that are generally regulated during infection we conducted a comparative transcriptome analysis of three nematode-trapping fungi infecting two nematode species. The analysis showed that the divergence in fungal interspecific gene expression was significantly larger than that related to the nematode host. We identified a core set of genes being expressed by all three fungi, and a more variable set being regulated depending on the fungal species or nematode host, respectively. The core set included several peptidases such as subtilisins and aspartic proteases but also ribosome-inactivating Ricin-B lectins. The variable set depending on the fungal species included fungal fruit-body lectins and D-mannose binding lectins. The host specific genes included glucosidases and genes encoding small secreted proteins
Internship at Worten Digitópia
This internship report for my master’s degree in Sound and Image at Universidade Católica Portuguesa is presented as a curricular internship report and describes all work developed at Worten Digitópia, who has provided me with the opportunity to learn and work in the area of electronic sound production at Casa da Música. The work portrayed in this report comprehend different projects ranging from pre-production and production for live orchestral concerts to sampling and programming for audio. This internship also allowed me to apply and explore skills I acquired during my years as a student at the School of Arts of Universidade Católica Portuguesa, as well as giving me the opportunity to explore other areas and acquiring new skills, to shape my vision as a professional and as an artist.Este relatório de estágio para o meu mestrado de Som e Imagem da Universidade Católica Portuguesa é apresentado como um relatório de estágio curricular e descreve todo o trabalho desenvolvido na Worten Digitópia, que me providenciou a oportunidade para aprender e trabalhar na área de produção eletrónica de som na Casa da Música. O trabalho apresentado neste relatório engloba diferente projetos indo desde pré-produção e produção para concertos orquestrais ao vivo até ao sampling e programação para áudio. Este estágio também me permitiu aplicar e explorar habilidades que adquiri durante os meus anos como estudante na Escola das Artes da Universidade Católica Portuguesa, assim como me dar a oportunidade de explorar outras áreas e adquirir novas aptidões, para moldar a minha visão como profissional e artista
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