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