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Unlocking epigenetic mechanisms in health and disease

Primary Supervisor: Dr Thomas Schalch, Leicester Institute of Structural and Chemical Biology

Secondary supervisor: Professor Shaun Cowley

PhD project title: Unlocking epigenetic mechanisms in health and disease

University of Registration: University of Leicester

Project outline:

The MIBTP student project is an integral part of our labs’ effort to understand epigenetic mechanisms that regulate the function of eukaryotic genomes. The structure of chromatin and the associated chromatin effector complexes with their epigenetic reader, writer and eraser modules are key factors in the regulation of transcription and genome maintenance, repair and replication. Our goal is to understand what regulates the activity how multi-protein chromatin effector complexes interact with nucleosomes, and how these interactions contribute to biological function. The mechanisms and biological role of histone methylation, acetylation and histone ubiquitination are key areas of interest in our labs. This project will provide training in biochemistry, structural biology, genome analysis and cell biology, thereby providing hands-on experience to develop the skills to uncover fundamental biological processes and to investigate how these processes are deregulated in pathological situations that can lead to developmental defects or cancer.

References:

  1. Stirpe A., Guidotti N., Northall S., Kilic, S., Hainard, A., Vadas, O., Fierz, B., Schalch, T. (preprint). SUV39 SET domains mediate crosstalk of heterochromatic histone marks. bioRxiv 2020.06.30.177071.
  2. Moraru, M and Schalch, T. (2019). Chromatin fiber structural motifs as regulatory hubs of genome function? Essays In Biochemistry, EBC20180065.
  3. Leopold K., Stirpe A. and Schalch, T. (2019). Transcriptional gene silencing requires dedicated interaction between HP1 protein Chp2 and chromatin remodeler Mit1. Genes & Development 33, 565-577.
  4. Job, G., Brugger, C., Xu, T., Lowe, B.R., Pfister, Y., Qu, C., Shanker, S., Baños Sanz, J.I., Partridge, J.F. and Schalch, T. (2016). SHREC Silences Heterochromatin via Distinct Remodeling and Deacetylation Modules. Molecular Cell, 62, 207–221. Article

BBSRC Strategic Research Priority: Understanding the Rules of Life: Structural Biology

    Techniques that will be undertaken during the project: 

    • Cloning
    • Protein expression and purification
    • Enzyme kinetics
    • CD, ITC and other biophysical techniques
    • Cryo-EM,
    • S. pombe genetics
    • Chromatin Immunoprecipitation (ChIP-seq)
    • RT-qPCR

    Contact: Dr Thomas Schalch, University of Leicester