Fumiko Esashi

Genome Stability and Evolution

In our lab, we investigate the mechanisms that drive changes in the genome during cell growth and dormancy. We are particularly interested in the trigger of these changes, how cells protect themselves against dangerous changes and, in what situations, they adapt to them for gain. By studying these processes, we hope to uncover new insights into the molecular basis of human diseases.

The stability and evolution of the genome are central to many living organisms for their continued growth, survival and reproduction. Commonly, a genome is referred to as the complete set of genetic information in an organism. However, the full decoding of the human genome revealed a plethora of seemingly non-functional repeat sequences, taking up more than half of the genomic DNA. It remains unclear to what extent such regions contribute to disease-causing genome instability or advantageous genome evolution.

Tackling this problem, we study triggers and regulation of an evolutionary highly conserved mechanism called homologous recombination (HR). HR can exchange genomic elements based upon ‘homologous’ (i.e. similar in position, structure, and evolutionary origin) DNA sequences. As such, it impacts genome stability either positively or negatively.

HR normally occurs during S and G2 phases of the cell cycle and, by using the replicated sister DNA as a repair template, can faithfully recover the missing genomic information. However, HR can also use a similar but non-allelic DNA as a repair template, and by doing so, exchange, amplify or delete repetitive regions of genomic DNA. Such non-allelic HR events could result in genome instability, but could conversely offer, in some situations, structural or functional robustness.

We aim to understand how HR is regulated in the context of the cell cycle and at regions of genomic DNA that are prone to break or recombine. We use and develop interdisciplinary approaches combining various state-of-the-art tools to investigate the impact of HR on genome stability. These include, but not limited to, genetics, molecular biology, microscopy imaging, biochemistry, bioinformatics and mathematical modelling.

Group members

  • Fumiko Esashi (Group leader)
  • Emoke Zsanett Gerocz (Research assistant)
  • Jacob Wall (PhD student)
  • Usman Mukhtar (Undergraduate student)
  • Irfan Mamun (PhD student)
  • Brian Leung (PhD student)
  • Santosh Kumer (Postdoc)
  • Ramazan GÜNDOĞDU (Postdoc)
  • Emily Graham (Postdoc)

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