Research Overview

My research goal is to understand the mechanism of chromosome maintenance, with a focus on pathways needed for accurate and robust replication of chromosomal DNA. 

Using both yeast and human cell lines, I have made important contributions in this research area, in particular the identification of Rif1-mediated Protein Phosphatase 1 (PP1) targeting to replication initiation proteins. I have demonstrated RIF1-PP1 controls the initiation of DNA replication via modulation of the phosphorylation status of MCM proteins in yeast (Hiraga et al. 2014 Genes & Development 28: 372-383) and human cells (Hiraga et al. 2017 EMBO Reports 18: 403-419).

Our group is also conducting research on how Rif1 protein protects chromosomes from damage during DNA replication stress (Hiraga et al. 2018 EMBO reports 19: e46222; Garzon et al. 2019 Cell Reports 27: 2558-2566; Watts et al. eLife 2020;9:e58020). These projects are expected to broaden our understanding of the mechanism ensuring integrity in human cells, and develop new methods to prevent and cure cancers.

We also recently discovered that Scaffold-attachment factor A (SAF-A; also known as HNRNPU), which is known to be an RNA-binding and chromatin-associated protein that regulates 3D chromatin structure, ensures robust DNA replication in human cells (Connolly et al. bioRxiv DOI: 10.1101/2021.03.22.436394).

We are using both baker's yeast and cultured human cells as model organisms. These cells share many fundamental mechanisms, despite they look very different in size, shape, and behaviour (and you will be surprised many of genes/proteins found in our cells also exist and play similar roles in tiny yeast cells). These organisms have both "pros" and "cons" as model organisms, and complement each other. I aim to gather strengths together from them to perform good research.

A PhD position is currently available.  See https://www.findaphd.com/phds/project/how-does-the-chromatin-and-rna-associated-protein-saf-a-support-chromosomal-dna-replication-and-promote-cancer/?p131409

Current Research

I am currently investigating the function of yeast and human RIF1 protein in:

• DNA replication
• Cellular response to replication stress
• Cell proliferation
• Protection of chromosomes from damage during DNA replication stress

I'm using both classical genetics and cutting-edge technologies such as ;

• Genetic engineering
• Genomics
• Proteomics
• Genome-wide ChIP
• Single-cell replication timing analysis
• Super-resolution microscopy

Collaborations

I am currently playing an important role in a collaboration involving Dr Berndt Müller, Prof. Anne Donaldson (University of Aberdeen), Dr Tony Ly and Prof. Angus Lamond (University of Dundee), Dr Simon Boulton (Crick Institute) and Prof. Peter Adams (Cancer Research UK Beatson Institute, University of Glasgow) in which we have carried out a proteomic examination of senescent human chromatin. I am also conducting international collaboration with Dr Ichiro Hiratani (RIKEN Center for Biosystems Dynamics Research, Japan), Dr Masato Kanemaki (National Institute of Genetics, Japan), Professor Chikashi Obuse (Osaka University, Japan) and Professor Katsuhiko Shirahige (University of Tokyo, Japan).

Funding and Grants

2019  Daiwa Anglo-Japanese Foundation Small Grant

2015-2020  Cancer Research UK Program Grant 'How does Rif1 ensure chromosome stability and can its removal prevent tumour cell survival?' (Principal Investigator: Prof A. Donaldson, Co-investigator: Dr S. Hiraga)

Teaching Responsibilities

Course co-ordinator for Honours Advanced Molecular Biology MB4050