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- Feizi, Amir, 1980, et al.
(författare)
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HCSD: The human cancer secretome database
- 2015
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Ingår i: Database : the journal of biological databases and curation. - : Oxford University Press (OUP). - 1758-0463. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- The human cancer secretome database (HCSD) is a comprehensive database for human cancer secretome data. The cancer secretome describes proteins secreted by cancer cells and structuring information about the cancer secretome will enable further analysis of how this is related with tumor biology. The secreted proteins from cancer cells are believed to play a deterministic role in cancer progression and therefore may be the key to find novel therapeutic targets and biomarkers for many cancers. Consequently, huge data on cancer secretome have been generated in recent years and the lack of a coherent database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer secretome data and secretory features for each identified protein.
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| 2. |
- Feizi, Amir, 1980
(författare)
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Systems Analysis of the Protein Secretory Pathway in Yeast and Human Cells
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cell was discovered by Robert Hooke in 1665, later in nineteen century the cell theory was developed as all organisms are composed of one or more cells. Since then, many tools and experimental methods have been developed to dissect and characterize the cell components which resulted in established solid scientific fields such as biochemistry, molecular cell biology and genetics. These fields provided us with accumulated reductionist knowledge of components and processes in different cells originated from organisms belonging to various kingdoms of life, as simple as prokaryotes to the higher eukaryals. By the advent of biotechnology these knowledge is used to change many aspect of our life. One of the most important cell processes that has been core to this revolution is secretory pathway which is responsible to put proteins in the cell surface or extracellular space. These protein which are called secretory proteins, encompass diverse range of proteins in each cell with critical roles in digestion, cell-cell communication, signaling, physiology, connectivity etc. Recombinant gene expression was the fruit of the revolution in molecular biology techniques such as PCR in 1970s and using of host cells secretory capacity. A decade after, expressing a heterologous (foreign) proteins in host cells have revolutionized healthcare, agricultural, fuel, food and waste industries. These cells include a wide range from bacteria, fungi, to insect cells and mammalian cells. Nowadays, there are hundreds of biopharmaceutical proteins in the market with many more under clinical trials. Sequencing of complete genomes and the availability of genome-scale reagents has changed the experimental strategies for determining gene function. Besides genome sequencing other high-throughput methods have been developed to measure transcription, translation and metabolites and therefore we are now facing a lot of data on different cellular processes that are collectively referred to as omics data. Analyzing this kind of data is inevitable demanding the use of computers integrated with statistical and mathematical algorithms. However, this is only the starting point, as all these entities in reality work together in a complex networks of interaction resulting in important biological systems which is called emergent properties. Analyzing omics data without integrating them in the context of network give us very little and unrealistic view of the cell. Here systems biology, which studies biological processes as complex systems in the context of their interaction, comes to play. Based on reductionist knowledge we have been somewhat successful in using secretory machinery to produce many different proteins. Also we know a lot how the malfunction of this pathway can results in serious diseases. As we are now able to measure the activity of secretory pathway as a whole system and connecting it with the activity of rest of the cell, we may be able to use systems biology to elevate our understanding of the protein secretory pathway to the systemic level which is todays bottle neck in both protein production and human diseases related to this pathway.
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| 3. |
- Fletcher, Eugene, 1986, et al.
(författare)
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RNA-seq analysis of Pichia anomala reveals important mechanisms required for survival at low pH
- 2015
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The product yield and titers of biological processes involving the conversion of biomass to desirable chemicals can be limited by environmental stresses encountered by the microbial hosts used for the bioconversion. One of these main stresses is growth inhibition due to exposure to low pH conditions. In order to circumvent this problem, understanding the biological mechanisms involved in acid stress response and tolerance is essential. Characterisation of wild yeasts that have a natural ability to resist such harsh conditions will pave the way to understand the biological basis underlying acid stress resistance. Pichia anomala possesses a unique ability to adapt to and tolerate a number of environmental stresses particularly low pH stress giving it the advantage to outcompete other microorganisms under such conditions. However, the genetic basis of this resistance has not been previously studied. Results: To this end, we isolated an acid resistant strain of P. anomala, performed a gross phenotypic characterisation at low pH and also performed a whole genome and total RNA sequencing. By integrating the RNA-seq data with the genome sequencing data, we found that several genes associated with different biological processes including proton efflux, the electron transfer chain and oxidative phosphorylation were highly expressed in P. anomala cells grown in low pH media. We therefore present data supporting the notion that a high expression of proton pumps in the plasma membrane coupled with an increase in mitochondrial ATP production enables the high level of acid stress tolerance of P. anomala. Conclusions: Our findings provide insight into the molecular and genetic basis of low pH tolerance in P. anomala which was previously unknown. Ultimately, this is a step towards developing non-conventional yeasts such as P. anomala for the production of industrially relevant chemicals under low pH conditions.
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