Genome Variation, Dynamics and Radiation Biology

Disruption of the Shelterin complex leads to telomere fusion (green) and so long chains of chromosomes (blue)are formed.

Germline and somatic mutation, and epigenetic modifications, are fundamental to the initiation and progression of cancer.  Leicester has internationally recognised strength in basic research into the mechanisms that underlie the dynamic nature of the human genome.  Mechanistic studies on crossover and conversion processes in the human germline and in the the model organism, yeast, are well established.  Some studies of genome variation focus on the dynamics of copy number variation (CNV) within populations and others apply the approaches used in the cancer setting.  Instability of telomeric DNA plays a key role in carcinogenesis, and is analysed in both normal and cancer cells.  In addition to mutagenesis, both through induction of DNA damage through oxidative stress and retroelement transposition is also a focus of active research.

Knowledge of genome dynamics can also be applied to cancer diagnosis, prognosis and the assessment of response to treatment.  There has been particularly success in identifying breakpoints involved in the initiation of a variety of haematological malignancies.  Genome-wide approaches to identifying DNA copy number changes are being exploited with a view to improving therapeutic outcomes.  Free DNA in  plasma is being used to monitor the progression of disease in women with breast cancer and in response to therapy.  Interactions are occurring across Departments and the MRC Toxicology Unit to translate basic research into genome dynamics and epigenetics into prognostic and therapeutic biomarkers for patient benefit.

Radiation biology research includes both academic staff and clinical oncologists.  Current research areas focus on investigation of the effect of DNA damage both on- and off-target.  These include radio-sensitivity and resistance, transgenerational mutation induction, and the identification of patients at risk of adverse effects.

Theme members associated with these areas are listed below:

Fundamental mechanisms of genome dynamics

• Badge, Borts, Brookes, Cooke, Dubrova, Evans, Gant, Hollox, Jeffreys, Jobling, May, Royle

Application of genome variation and epigenetics in cancer detection, diagnosis and prognosis

• Badge, Brookes, Dyer, Gant, Hollox, Pringle, Royle, Saldanha, Shaw

On- and off-target effects of radiotherapy

• Barwell, Dubrova, Jones, Symonds, Talbot