Organismal development depends on the linear genome sequence and its thousands of genes controlled by millions of regulatory sequences. The three-dimensional (3D) chromatin architecture that orchestrates the interplay between these regulatory elements and their target genes also plays an essential role in correct expression of developmental genes. However, compared to our knowledge of the regulatory sequences, the understanding of the 3D genome organization in human and other eukaryotes is still limited. Recent advances in technologies to map the 3D genome architecture have accelerated the pace of discovery. We also know that there are several classes of architectural proteins involved in the 3D organization of chromatin, including proteins such as cohesins, insulators and chromatin remodelers. These synergize to ensure correct 3D genome organization and consequently, efficient co-expression or co-repression of developmental genes required to reprogram cells during differentiation and induction of pluripotent stem cells.
The Percipalle lab in the Science Division, New York University Abu Dhabi, has a vacancy for a highly motivated researcher with expertise in biochemistry, cell and molecular biology and a keen interest to work on the 3D organization of the mammalian genome during the process of differentiation. Our main goal is to understand how the dynamic architecture of the genome prompts activation or repression of entire gene programs that ultimately lead cells to acquire specific identities. Recently, our lab discovered that cytoskeletal proteins such as actin and myosin are important regulators of 3D genome organization. In the cell nucleus, actin is required for correct expression of genes involved in neurogenesis through a mechanism that regulates the spatial distribution of chromatin (Xie et al., 2018, FASEB J; Xie et al., 2018, PLOS Genetics). Following up on these observations, to get further insights into these mechanisms we have developed three cellular differentiation models to study neurogenesis, adipogenesis and osteogenesis based on direct reprograming of embryonic fibroblasts to neurons, fat cells and osteocytes, respectively. To investigate the precise role of actin and myosin in genome regulation in differentiation we utilize embryonic fibroblasts isolated from knockout mouse models for actin and a form of myosin 1c that localizes to the cell nucleus. To address their role in genome organization during differentiation, we routinely apply direct reprograming and study how gene expression is affected using a combination of cell and molecular biology approaches, advanced imaging and genome-wide analyses such as RNA-seq, ChIP-seq and ATAC-seq.
In the proposed project we are particularly interested in applying protocols to produce induced pluripotent stem cells (iPSCs) and study how actin and myosin contribute to changes in 3D genome organization by conformation capture technology combined with deep sequencing (Hi-C-seq). Results from these studies have potential for the identification of novel elements that control genome organization during formation of iPSCs. Integration of these technologies also opens unprecedented potential for understanding the mechanisms that control the mammalian genome, how these mechanisms may also impact on genome stability and integrity and how this knowledge may be applied to personalized medicine.
Faculty name and title: Piergiorgio Percipalle, Associate Professor of Biology
Responsibilities of the position:
development of a protocol to generate induced pluripotent stem cells from mouse embryonic fibroblasts
test the protocol by advanced imaging and genome wide analyses
BSc/MSc in biological sciences or related disciplines
Some experience in mammalian cell culture
mammalian cell culture proficiency
DNA and protein gel electrophoresis
molecular biology techniques such as RNA extraction
understanding of genomics and bioinformatics
Applicants to provide:
statement of research interest
Reprints of transcripts
Names and contact information of two academic referees
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