RESEARCH BACKGOUND:

Female cells contain two X chromosomes while male cells contain only one, and to balance the X-gene dose in female cells one X-chromosome copy is kept transcriptionally silenced by the process of X-inactivation. At the same time, the remaining active X chromosome is hyper activated to balance the gene dose with the diploid autosomal part of the genome. Because of these chromosome-wide features, the X-chromosome is a truly remarkable system for dissecting major mechanisms of transcriptional regulation.

By characterizing the states and epigenetic framework of X-chromosome inactivation, we may reveal fundamental features of transcriptional regulation and systems biology. To expose the mechanisms of dosage compensation, we employ 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. Reinius and colleagues recently 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, bioRxiv 2019 etc., see www.reiniuslab.com/Publications). The expected outcome of the research is of broad biological significance, and has the potential to reveal molecular mechanisms underlying variable expressivity and incomplete penetrance of X-linked genetic disorders.



YOUR ROLE:

We are seeking a highly motivated MSc student to join our research team. The aim of your project is to investigate the regulation and dynamics of the major gene regulation processes X-chromosome inactivation and Hyper activation, in human and mouse cells. Cells and tissues are collected for massively parallel sequencing during various developmental processes and stages in which major transitions in X-chromosome expression occurs. You will get first-hand access to these immense datasets, including data from single-cell RNA-seq and chromatin assays, generated in our lab. Your task is to identify regulatory patterns and transcriptional switches during the establishment of X-inactivation as well as hyper activation. The project has the potential to reveal fundamental features of mammalian gene regulation.



REQUIREMENTS:

This task requires adequate scripting skills in Python and/or R, and basic bioinformatics skills. Experience of bash/shell is a plus. A strong interest and fascination in molecular biology is necessary.



LEARNING OUTCOMES:

You will gain deep knowledge in how RNA/DNA-sequencing datasets (including single-cell RNA-seq) are generated – from biological cells to sequence reads in silico. You will further learn how to handle and analyze large transcriptional datasets, how to perform downstream bioinformatics analyses, and finally how to visualize and present data to a high scientific standard. Our lab runs an in-house computational Linux server that you will have direct access to and experience how to use.



OUR LAB:

Please visit our homepage www.reiniuslab.com to see what’s going on in the lab.



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.