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Accessing the Druggable Genetic Programs Governed by Mammalian bHLH-PAS Transcription Factors (360G-Wellcome-210664_Z_18_Z)

We have recently projected that the human bHLH-PAS proteins form a class of transcription factors with great therapeutic promise, and propose to subject this family to in-depth chemical and functional explorations. The sixteen members of this family are functionally non-redundant and have genetic links to cancers, metabolic syndromes, inflammatory diseases, and psychiatric conditions. They share common architectural features that include a conserved DNA-binding domain and dual PAS domains. Our specific aims are: 1. Identify chemical ligands for members of the human bHLH-PAS family. 2. Determine the ligand-dependent genomic signatures and cellular pathways governed by family members. 3. Probe the mechanisms by which chemical ligands manifest their activities through this family. These studies allow us to transition from having visualized their ligand binding properties to employing chemical tools for interrogating and manipulating their functional activities as transcription factors.

£2,161,828

10 Apr 2018

Grant details
Amount Awarded 2161828
Applicant Surname Rastinejad
Approval Committee Science Interview Panel
Award Date 2018-04-10T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 210664/Z/18/Z
Lead Applicant Prof Fraydoon Rastinejad
Planned Dates: End Date 2023-09-01T00:00:00+00:00
Planned Dates: Start Date 2018-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
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