The chemical biology and function of natural modified DNA bases in genomes (360G-Wellcome-209441_Z_17_Z)

£2,198,391

<p>I aim to elucidate the function of natural, chemically-modified DNA bases in the genomes of model organisms, using chemical&nbsp;biology and physical science approaches on genomic DNA. Modified bases are of fundamental importance to transcriptional programming and cell identity during and after development. The role of the cytosine derivative 5-formylcytosine and its influence on nucleosome formation, active enhancers, transcription and cell identity will be one area of focus to build mechanistic understanding, following on from hypotheses derived from our prior work. There will also be an investigation of 5-carboxycytosine&nbsp;and 5-hydroxymethyluridine and their potential links with transcription regulation.&nbsp; For other modified bases, such as N6-methyladenine, we will develop and use new chemical mapping/sequencing methods to elucidate their function in mammalian systems. The programme will include a systematic discovery of other&nbsp;natural DNA base modifications, building on and augmenting chemical methodologies I have developed to discover and profile modified bases in RNA.&nbsp; The function of newly identified base modifications will be investigated during the programme. The insights provided from these fundamental studies may have far-reaching consequences for normal biology and disease states.</p> <p>&nbsp;</p> <p>Keywords: chemical biology, nucleic acids, DNA, modified bases, epigenetics, sequencing</p>

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Grant Details

Amount Awarded 2198391
Applicant Surname Balasubramanian
Approval Committee Science Interview Panel
Award Date 2017-11-28T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 209441/Z/17/Z
Lead Applicant Prof Sir Shankar Balasubramanian
Planned Dates: End Date 2023-12-01T00:00:00+00:00
Planned Dates: Start Date 2018-12-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England