Class IA PI3Kinase Regulatory Subunit, p85α, Mediates Mast Cell Development through Regulation of Growth and Survival Related Genes

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1A PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes

Reflections on integrating bioinformatics into the undergraduate curriculum:The Lancaster experience

Bioinformatics is an essential discipline for biologists. It also has a reputation of being difficult for those without a strong quantitative and computer science background. At Lancaster University, we have developed modules for the integration of bioinformatics skills training into our undergraduate biology degree portfolio. This article describes those modules, situating them in the context of the accumulated quarter century of literature on bioinformatics education. The constant evolution of bioinformatics as a discipline is emphasized, drawing attention to the continual necessity to revise and upgrade those skills being taught, even at undergraduate level. Our overarching aim is to equip students both with a portfolio of skills in the currently most essential bioinformatics tools and with the confidence to continue their own bioinformatics skills development at postgraduate or professional level

Erratum : Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

This corrects the article DOI: 10.1038/nm.4484