Genomic Instability

Professor Munira Kadhim

In everyday life we are continuously exposed to radiation from a wide variety of sources, both natural and artificial. Radiation is known to cause a range of cellular damage and activate a number of repair pathways; it is also known to induce delayed genomic instability, which is a hallmark of tumorigenesis. Our work aims to study the potential impact of such exposure on human health by studying the mechanism(s) underlying this instability phenomenon.

Radiation biology – Genomic instability, bystander effects and beyond

In recent years, our understanding of radiation biology has experienced a paradigm shift from deterministic ‘hit-effect’ relationships to complex ongoing ‘cellular responses’, such as genomic instability and bystander effects.

The central dogma of radiation biology is that radiation energy must be deposited in the nucleus in order to produce a biological effect. However, there is a wealth of evidence which challenges this classical paradigm, collectively described as non-targeted effects of radiation e.g. genomic instability (GI) (delayed effects, transmissible to multiple generations post-exposure) and bystander effects, in which signals from irradiated cells induce damage in neighbouring non-irradiated cells. Whilst the range of non-targeted effects of radiation are well described, both in vitro and in vivo at the cellular and chromosomal level, there remain a number of unanswered questions at the molecular/genetic level. The main focus of the Genomic Instability Research Group is to better understand how GI is initiated and perpetuated in both irradiated and bystander populations. Other topics of interest include: What is the mechanistic link between the two populations? What signalling pathways are involved? What factors are associated with the genetic variability of non-targeted effects? What are the implications for health risks?

We believe that a deeper knowledge of these mechanisms/responses will yield a better understanding of non-targeted effects of ionizing radiation on the relevance of such processes for human health, specifically radiation risk assessment and cancer therapy and will suggest new strategies for health protection and therapy.

The Genomic Instability Research Group primarily utilise cytogenetics (analysis of metaphase chromosomes) encompassing a range of microscopy techniques (Giemsa staining, mFISH, immunofluorescence, monitoring calcium flux) and molecular approaches (Comet assay, ELISA, viability assays) to study initiation and perpetuation of cellular and subcellular damage in cultured cells. We have an excellent cell culture facility and a well equipped laboratory for molecular and cell biology. The group has Comet and mFISH imaging systems, and also has access to the School’s central microscopy facilities (including confocal and electron microscopes).

People

  • Deborah Bowler – Senior research assistant
  • Scott Bright - PhD student

Funding

Collaborations

UK

  • Mark Hill, Gray Institute of Radiation Oncology and Biology, Oxford, UK
  • Kai Rothkamm, Health Protection Agency, Harwell Campus, UK
  • Liz Ainsbury, HPA, Harwell Campus, UK
  • Sabah Jassim and Kenny Langlands, University of Buckingham, UK

Members of the NOTE EU consortium

  • Fiona Lyng, RESC, Ireland
  • Géza Sáfrány, NRIRR, Hungary
  • Rafi Benotmane, Belgian Nuclear Research Centre
  • Virpi Launonen, STUK, Finland
  • Mark Little, Imperial College, UK

USA

  • Lora Green and Daila Gridley, Loma Linda University, USA
  • Mansoor Ahmed, Miller School of Medicine, University of Miami, USA
  • Mohan Natarajan, University of Texas Health Science Center
  • Robert Schiestl, UCLA, USA

Publications

Prof Munira Kadhim

CONTACT US

Prof Munira Kadhim
mkadhim@brookes.ac.uk
+44 (0) 1865 483613
Publications

Mk Group comet

Mfish

Exosome