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Drug Target Discovery for Cellular Rejuvenation by ‘Driver’ Clocks | Daniel Ives, Shift Bioscience
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Foresight Biotech & Health Extension Meeting sponsored by 100 Plus Capital
Daniel Ives, Shift Bioscience, Shift Bioscience
Drug target discovery for cellular rejuvenation by the application of ‘driver’ clocks to cell reprogramming
At Shift Bioscience Daniel is making drugs for cellular rejuvenation in humans through the application of machine-learning 'driver' clocks to cellular reprogramming.
Daniel was inspired to pursue a Longevity mission in 2009 after reading Aubrey de Grey’s 2007 book ‘Ending Aging’. As a U. Cambridge PhD student, Daniel joined Ian Holts group at the Mitochondrial Biology Unit to pursue damage-removal strategies for mitochondrial DNA mutations, which cause rare mitochondrial disease and are sufficient to accelerate ageing phenotypes in mouse models. Harnessing publicly available transcriptome data from the NCBI GEO database, Daniel used a computationally guided screen to identify small-molecule tools that eliminate mitochondrial DNA mutations. Daniel followed Ian to the Crick Institute to further validate these small molecule-tools (publication-pending).
In 2016 Daniel left the Crick Institute and personally funded ageing-focused experiments using local contract research organisations (Total Scientific, now RxCelerate). Once friend and family financing was exhausted, Daniel approached Cambridge angel Jonathan Milner and with his support, Shift Bioscience was founded to commercialise mitochondrial drugs for age linked diseases, quickly embracing a breakthrough ageing biomarker - DNA methylation or epigenetic ageing clocks. These clocks clarified the role of mitochondrial DNA mutations in physiological ageing and pivoted Shift to a first-principles approach to drug-target discovery for rejuvenation.
Daniel helped guide Shift intern Brendan Swain (U. Cambridge PhD student) to develop a single cell ageing clock built from transcriptome data. This enabled a CRISPR screen for ageing on the 10X Genomics Chromium machine, but more excitingly, the constituent genes of the clock were enriched for functional 'drivers' of ageing phenotypes, suggesting this was a causal or 'driver' clock for ageing. The same clock methodology was then used to extract non-pluripotent candidate drivers of rejuvenation from a cellular reprogramming time-course (OSKM) and we are now gearing up to validate these candidates!
Foresight Institute’s Biotech and Health Extension Group
A group of scientists, entrepreneurs, and institutional allies, connected by a virtual group, who meet monthly to spur field-wide progress on technologies that fight aging and increase human healthspan.
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