the Reinius lab
OUR RESEARCH is focused on revealing key features of gene regulation, and in particular the regulation of active and inactive chromatin states. A main topic in the lab is X-chromosome inactivation and Dosage Compensation. The X chromosome is a unique genetic environment. Female cells contain two X chromosomes while male cells contain only one. To balance the X-gene dose in female cells one X copy is kept transcriptionally silenced by the process of X-chromosome inactivation. This is achieved by remarkable remodeling of the inactive X chromosome, which drastically changes its chromatin structure, methylation patterns, and three-dimensional conformation – ultimately suppressing the expression of most of its genes. By characterizing the epigenetic framework of X-chromosome inactivation, we may reveal fundamental features of gene regulation and systems biology. During the last years Reinius and colleagues pioneered the use of single-cell RNA-seq in the study of X-inactivation (Science 2014, Nature Reviews Genetics 2015, Cell 2016, Nature Genetics 2016 etc., see Publications ). Currently the Reinius lab is working to determine the X-inactive landscape across a wide range of in vivo tissues and cell types. This is accomplished by a comprehensive synthesis of newly developed concepts and techniques, including single-cell RNA-sequencing, chromatin accessibility and modification assays, mouse genetics and transgenics, and recently advanced computational methods for the analysis of allele-specific gene expression. The expected outcome of the research is of broad biological significance, and may reveal gene-regulatory features underlying variable expressivity and incomplete penetrance of X-linked genetic disorders.
- A MECHANISTIC BREAKTHROUGH: Recently, we have been studying X-chromosome upregulation. The single active X-chromosome in cells is hyper activated to balance the gene dose with the diploid autosomal part of the genome. We discovered that this hyper activation is achieved by increase burst frequencies for X-linked genes (Preprint: Transcriptional kinetics of X-chromosome upregulation). This represents a Major Breakthrough to the Mechanism of Dosage Compensation!
Advancing RNA/DNA sequencing technology: High-throughput sequencing is key in our work, and is increasingly utilized in Medicine. We are working to invent and improve methods for RNA and DNA sequencing – tailoring the methods to maximize the information yield in the context of specific assays.
OPEN POSITIONS: >>>One PhD position open!<<<
LOCATION: The Reinius lab is placed at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet; an international and vibrant research environment. Our Division, is located at Biomedicum, KI Solna Campus, a purpose-built facility for experimental medical research. It hosts research groups with diverse backgrounds, forming a unique cluster of expertise in Molecular Biology and Biomedicine.
Karolinska Institutet, Solna, Stockholm