Investigating the epigenetic control of female-biased autoimmune disorders

Garvan Institute of Medical Research, University of New South Wales Sydney, Australia

Brief overview:

Autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, present with a strong gender bias, with 80% of all patients being women. However, the molecular basis for such disparity remains elusive.

Autoimmunity is underpinned by the expansion of autoreactive B cells and production of autoantibodies, which attack the body’s own cells, resulting in chronic inflammation and tissue damage. Recent discoveries revealed that B cells in female patients with autoimmunity display aberrant re-activation of immune genes on the inactive X chromosome. It is well established that inactivation of the second X chromosome in female cells is controlled by a fundamental epigenetic process known as X chromosome inactivation. It is widely studied in the context of embryonic development; however, overwhelmingly little is known about (i) the epigenetic mechanisms that regulate X chromosome inactivation in healthy adult cells, including B cells, and (ii) how these mechanisms are mis-regulated in disease.

This project aims to (i) define the mechanisms and function of the dynamic epigenetic regulation of the inactive X chromosome in normal female B cells and (ii) interrogate the role of aberrant epigenetic changes underpinning X chromosome re-activation in female-biased autoimmunity.

Benefits:

–      NHMRC-funded and supported project placed in a stimulating, diverse and collaborative interdisciplinary research environment

–      Opportunities for on-going training and skill development in cutting-edge epigenomic technologies, genome editing and immunological techniques including:

• Single cell transcriptome and DNA methylome / hydroxymethylome profiling (e.g. smart-seq2, scM&T-seq)
• Long read allele-specific RNA sequencing (10x Genomics combined with Oxforrd Nanopore Technologies and Whole Genome Sequencing)
• Genome-wide profiling of histone post-translational modifications (e.g. ChIP-seq, CUT&RUN)
• CRISPR interference / activation screens in immune cell lines
• High-parameter flow cytometry of mouse and human immune cells

–      Opportunities to develop bioinformatics skills for next generation sequencing data analysis

–      Supportive environment for career development inside and outside academia

–      Opportunities to present at national and international conferences

The Successful Candidate:

–      Highly motivated domestic or international candidate with a strong background in molecular biology and epigenetics

–      BSc (hons) or MSc or equivalent degree

–      Expertise in basic wet lab techniques including DNA/RNA extraction, western blot, qPCR, cell culture and cell transfection

–      Next generation sequencing library preparation and data analysis skills are desired but not compulsory

–      High-level analytical and critical skills

–      Ability to maintain thorough laboratory records

–      An interest and motivation to gain relevant research expertise

–      Excellent organisational, written, and verbal communication skills.

If you are interested in the project please send your c.v. and cover letter to Dr Ksenia Skvortsova: [email protected]