Exploiting transcription of repetitive DNA to study early events in colorectal cancer (360G-Wellcome-210911_Z_18_Z)

£455,076

Molecular changes occurring before cancer can be detected by commonly used methods provide potential biomarkers for early detection if routine screening were in place. To date, research has focused mainly on unique DNA largely disregarding the 55% composed of repetitive sequences like LINE-1s. LINE-1s are usually silenced in normal tissues but active in cancer and are best known for their ability to move to other locations in the genome with obvious deleterious implications. Mobilisation first requires activation of LINE-1’s promoters, but, intriguingly, those of both mobile and immobile LINE-1s become active in cancer. To fully understand the functional consequences of this transcriptional activity requires overcoming the challenges of studying individual LINE-1s. Using innovative approaches, we identified a LINE-1 whose activation is linked to silencing of a tumour suppressor gene and whose product can be detected in the blood of colorectal cancer patients. I will build on this knowledge to determine to determine why and which LINE-1’s promoters are active in colorectal cancer and what are the effects of this activation on neighbouring genes. I will examine in liquid biopsies the biomarker potential of the novel, aberrantly expressed genes so identified, with a long-term aim to help refine current tests.

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Grant Details

Amount Awarded 455076
Applicant Surname Tufarelli
Approval Committee Basic Science Interview Committee
Award Date 2018-04-25T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Career Re-Entry Fellowship
Internal ID 210911/Z/18/Z
Lead Applicant Dr Cristina Tufarelli
Partnership Value 455076
Planned Dates: End Date 2024-08-01T00:00:00+00:00
Planned Dates: Start Date 2018-09-03T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East Midlands
Sponsor(s) Prof Alison Goodall