Biology subjects

Ibrahim, S.

Publications and source records attributed to Ibrahim, S..

4 recordsLinked to original sources

bioRxiv2018

Pathway maps enable straightforward yet customized and semi-automated yet insightful analyses of omics data

To explore the molecular processes underlying some biological theme of interest based on public data, gene lists are used herein as input for the construction of annotated pathway maps, employing Cytoscape apps, and then high-throughput (\"omics\") gene expression data are overlaid onto these maps. Seeded with a published set of marker genes of the senescence-associated secretory phenotype and the genes of the cellular senescence KEGG pathway, a gene/protein interaction network and annotated clusters (a \"pathway map\") of cellular senescence are derived. The map can be amended, by adding some application-specific genes, and overlaid with gene expression data describing cellular senescence of fibroblasts and with disease-related gene expression data associated with prostate and pancreatic cancer, and with ischemic stroke, allowing insights into the role of cellular senescence in disease. Some gene expression data are derived from the \"Biomarker Benchmark repository\". The pathway map approach can be followed in principle for any biological theme of interest, fostering much-needed independence from the investigator-biased expert networks usually used for overlaying gene expression data.

genomics↗

bioRxiv2018

Astroplastic: A start-to-finish process for polyhydroxybutyrate production from solid human waste using genetically engineered bacteria to address the challenges for future manned Mars missions

Space exploration has long been a source of inspiration, challenging scientists and engineers to find innovative solutions to various problems. One of the current focuses in space exploration is to send humans to Mars. However, the challenge of transporting materials to Mars and the need for waste management processes are two major obstacles for these long-duration missions.\n\nTo address these two challenges a process called Astroplastic was developed that produces polyhydroxybutyrate (PHB) from solid human waste, which can be used to 3D print useful items for astronauts. PHB granules are naturally produced by bacteria such as Ralstonia eutropha and Pseudomonas aeruginosa for carbon and energy storage. The phaJ, phaC, and phaCBA genes were cloned from these native PHB-producing bacteria into Escherichia coli. These genes code for enzymes that aid in PHB production by converting products of glycolysis and {beta}-oxidation pathways, such as acetyl-CoA and enoyl-CoA, into PHB. To ensure a continuous PHB production system and to eliminate the need for cell lysis to extract PHB, recombinant E. coli was engineered to use the genes in its natural type I secretion system to secrete PHB. The C-terminal of the HlyA secretion tag was fused to phasin (PhaP), a protein originally from R. eutropha. Phasin-HlyA electrostatically binds PHB granules and transports them outside of the cell.\n\nIn addition to genetically engineering bacteria, a concept for start-to-finish PHB production process was designed. Integrating expert feedback and experimental results, conditions for each step of the process including the collection and storage of waste, volatile fatty acid (VFA) fermentation, VFA extraction, PHB fermentation, and PHB extraction were optimized. The optimized system will provide a sustainable and continuous PHB production system, which will address the problems of transportation costs and waste management for future space missions.\n\nFinancial DisclosureMindfuel Science Alberta Foundation Genome Alberta GenScript Polyferm Canada GeekStarter Alberta Integrated DNA Technologies University of Calgary University of Calgary Cumming School of Medicine University of Calgary Bachelor of Sciences University of Calgary Schulich School of Engineering University of Calgary OBrien Centre for the Bachelor of Health Sciences City of Calgary Alberta Innovates The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\nCompeting InterestsThe authors have declared that no competing interests exist.\n\nEthics StatementN/A\n\nData AvailabilityAll data are freely available without restriction.

synthetic biology↗

bioRxiv2018

The role of AP-1 in self-sufficient proliferation and migration of cancer cells and its potential impact on an autocrine/paracrine loop.

The activating protein-1 (AP-1) family members are highly expressed in invasive cancers, but the consequences of this are not completely understood. The aim of this study was to explore the significance of elevated levels of AP-1 family members under conditions that restrict growth. We observed that invasive MDA-MB-231 cells express high levels of Fra-1, c-Jun and, Jun-D during serum starvation and throughout the cell cycle compared to non-tumorigenic and non-invasive cell lines. We then analyzed Fra-1 levels in additional breast and other cancer cell lines. We found a correlation between the high levels of Fra-1 during serum starvation and the ability of the cells to proliferate and migrate under these conditions. Utilizing a dominant negative construct of AP-1, we demonstrated that proliferation and migration of MDA-MB-231 in the absence of serum requires AP-1 activity. Finally, we observed that MDA-MB-231 cells secrete factors(s) that induce Fra-1 expression and migration in non-tumorigenic and non-metastatic cells and that both the expression of and response to these factors require AP-1 activity. These results suggest the presence of an autocrine/paracrine loop that maintains high Fra-1 levels in aggressive cancer cells, enhancing their proliferative and metastatic ability and affecting neighbors to alter the tumor environment.

cancer biology↗

bioRxiv2017

Combination of mitochondrial tRNA and OXPHOS mutation reduces lifespan and physical condition in aged mice

Mutations in the mitochondrial DNA (mtDNA) are widely known to impact on lifespan and tissue integrity. For example, more than 250 pathogenic mtDNA mutations are known, many of which lead to neurological symptoms. In addition, major neurodegenerative diseases share key components of their etiopathogenesis with regard to mtDNA mutations, mitochondrial dysfunction and oxidative stress. In our study we used a set of conplastic mouse models carrying stable point mutations in mitochondrial genes of transfer RNA (tRNA) and oxidative phosphorylation (OXPHOS)-proteins. We analyzed the impact of these mutations on complex traits like lifespan, learning and memory in the ageing process. The combination of both point mutations in the OXPHOS complex IV gene and adenine insertions in the mitochondrially encoded tRNA arginine (tRNA-Arg) gene (mt-Tr) leads to an age-dependent phenotype with elevated mitochondrial superoxide production in the neocortex. Mice with this combination of tRNA and OXPHOS mutations show significantly reduced lifespan and poor physical constitution at the age of 24 months, whereas single point mutations in OXPHOS or mt-tRNA(Arg) do not have this impact. Therefore, we suggest a synergistic effect of these mutations.

developmental biology↗