Project description:To understand the gain-of-toxicity of unprocessed prelamin A, we sought to identify the specific binding proteins of prelamin A that do not interact with mature lamin A. Because prelamin A is specifically localized to the nuclear envelope, we used ascorbate peroxidase 2 (APEX2)-based proximity labelling combined with mass spectrometry, which allows for temporally and spatially resolved proteomic mapping, to isolate the specific binding proteins of prelamin A.
Project description:To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.
Project description:Intrahepatic biliary and arterial development proceed with complex orchestrations involving Notch, TgfB, Wnt and Vegf signaling within the portal tracts of the liver. These pathways coordinate morphogenesis and remodeling temporally and spatially from mid-gestation through early postnatal life. We used microarrays to examine changes in remodeling/differentiation programs in portal tracts at 1 week postanally, comparing Jag1+/-Rfng+/- and controls.
Project description:Grain filling and proper grain development are essential biological processes in the plant’s life cycle, which majorly contributes to the final seed yield and quality in all cereal crop. However, very scarcely this knowledge is available in the literature regarding how the different wheat grain components contribute to the overall development of the seed. We performed a proteomics and metabolomics analysis in four different developing components of the wheat grain (seed coat, embryo, endosperm and cavity fluid) to characterize molecular processes during early and late grain development. In-gel shotgun proteomics analysis in 12, 15, 20 and 25 days after anthesis (DAA) lead us to identify and quantify 15,484 proteins out of which 410 differentially expressed proteins (DEPs) were identified in the seed coat, 815 in embryo, 372 in endosperm and 492 in cavity fluid. The abundance of selected protein candidates revealed spatially and temporally resolved protein functions associated with development and grain filling. Multiple proteins such as pyruvate phosphate dikinase (PPDK) and 14 -3- 3 undergo a major change in abundance during wheat grain development. Proteins binned into the functional category of cell growth /division were highly expressed during early stages (12 and 15 DAA) whereas those of starch biosynthesis in the middle or late stages. At the metabolome level all tissues and especially the cavity fluid showed highly distinct metabolite profiles. The tissue specific data are integrated with biochemical networks to explore a comprehensive map of molecular processes during grain filling and developmental processes.
Project description:Intrahepatic biliary and arterial development proceed with complex orchestrations involving Notch, TgfB, Wnt and Vegf signaling within the portal tracts of the liver. These pathways coordinate morphogenesis and remodeling temporally and spatially from mid-gestation through early postnatal life.
Project description:In this study, through coupling of our ISDoT tissue decellularisation technology with quantitative mass spectrometry, we explored the changing tumour matrisome during mammary tumourigenesis in the PyMT breast cancer model compared to age-matched healthy control mammary gland