Kaiser V.B.,University of Edinburgh |
Svinti V.,University of Edinburgh |
Prendergast J.G.,Roslin Institute |
Chau Y.-Y.,University of Edinburgh |
And 28 more authors.
Human Molecular Genetics | Year: 2015
Homozygous loss of function (HLOF) variants provide a valuable windowon gene function in humans, aswell as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown-as are the phenotypic effects of losing function for most human genes. Here, we make use of 1432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, whichwe showare enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to showthat most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation. The Author 2015.
Iglesias J.M.,Regulation of Cell Growth Laboratory |
Iglesias J.M.,Synpromics Ltd |
Leis O.,Regulation of Cell Growth Laboratory |
Ruiz E.P.,Regulation of Cell Growth Laboratory |
And 14 more authors.
Frontiers in Oncology | Year: 2014
The striking similarity displayed at the mechanistic level between tumorigenesis and the generation of induced pluripotent stem cells and the fact that genes and pathways relevant for embryonic development are reactivated during tumor progression highlights the link between pluripotency and cancer. Based on these observations, we tested whether it is possible to use a pluripotency-associated transcriptional reporter, whose activation is driven by the SRR2 enhancer from the Sox2 gene promoter (named S4+ reporter), to isolate cancer stem cells (CSCs) from breast cancer cell lines. The S4+ pluripotency transcriptional reporter allows the isolation of cells with enhanced tumorigenic potential and its activation was switched on and offin the cell lines studied, reflecting a plastic cellular process. Microarray analysis comparing the populations in which the reporter construct is active versus inactive showed that positive cells expressed higher mRNA levels of cytokines (IL-8, IL-6, TNF) and genes (such as ATF3, SNAI2, and KLF6) previously related with the CSC phenotype in breast cancer. © 2014 Iglesias, Leis, Pérez Ruiz, Gumuzio Barrie, Garcia-Garcia, Aduriz, Beloqui, Hernandez-Garcia, Lopez-Mato, Dopazo, Pandiella, Menendez and Martin.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 1.58M | Year: 2016
Evolving therapeutic approaches of cell and gene therapy are harnessing the power of viruses in order to modify genomes of cells to produce a therapeutic effect. Such therapies are starting to show efficacy in the clinic, but one of the key challenges to their widespread use is the ability to make large quantities of virus at a low cost. This project seeks to address this challenge by creating new methods of producing large quantities of virus at a low cost. It brings together Synpromics, a synthetic biology company based in Edinburgh, and the Cell Therapy Catapult, one of the UK’s network of Catapult centres focused on developing and growing a cell and gene therapy industry in the UK.
Synpromics Ltd | Date: 2015-10-23
Biological materials including genetic constructs, especially synthetic promoters and vectors; nucleic acids; materials for the construction of genetic constructs, especially synthetic promoters and vectors; cells, viruses and other carriers including such genetic constructs. Biological preparations for medical purposes; biological preparations for veterinary purposes. Agricultural, aquacultural, horticultural and forestry products; seeds; natural plants and flowers; propagation material. Biotechnological research and development services, including: design and provision of biological materials including genetic constructs, especially synthetic promoters and vectors, cells, viruses and other carriers including such genetic constructs; analysis and profiling of gene expression; technical information services in relation to the aforesaid and in respect of the construction of genetic constructs, especially synthetic promoters and vectors, cells, viruses and other carriers including such genetic constructs. Medical services; veterinary services.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 241.60K | Year: 2013
Enhancing methods of protein expression is fundamentally important to new drug development and the efficient production of biopharmaceuticals. The consortium aims to develop a novel means of designing and constructing synthetic promoters that can be employed on an industrial scale to drive the expression of proteins for commercial applications. This will be achieved by combining the synthetic promoter design capabilities of Synpromics with improved DNA assemble methodology from Genabler and systems biology expertise from the SynthSYS institute of the University of Edinburgh. The project will yield a novel platform technology that can be used to create synthetic promoters with multiple applications across the biotech sector. This initial feasibility study will incorporate disparate expertise from the three partners to construct synthetic promoters that can enhance the production of proteins in mammalian cell culture systems, with a view to improve upon protein yield and quality.