If you had been born a century ago, you would have been likely to die around the age of 50. Today men typically survive into their late 70s and women into their early 80s. But these longer lives come at a price.
Many older people suffer from ill-health which blights their later years. This is difficult for them, their families and for society as a whole. As our populations continue to age they are putting healthcare systems under immense and unsustainable strain.
The answer? Cellular reprogramming, a promising technology which will underpin the rapid development of new treatments for a range of diseases associated with old age, such as neurodegenerative diseases, liver disease and sight loss.
Our aim is to identify safe rejuvenation factors that reset cells and tissues to a youthful state, with the help of our cell simulation models. This opens the door to bringing cell reprogramming therapeutics into clinical trials. Rather than merely mitigating symptoms, these new therapeutics will be disease-modifying. They will diminish the severity of many age-related illnesses.
“You can take a cell from an 80-year old and, in vitro, reverse the age by 40 years. There is no other technology that can do that. What’s more, reprogramming is a key process that occurs naturally when a fertilized egg turns into an embryo and, nine months later, leads to a fresh-faced baby. Somehow, the DNA of the parents is scrubbed, renewed, and restarted. Reprogramming is one of the experiments that has been reproduced the most.” Alejandro Ocampo, MIT Technology Review, Sep 2021
In 2012 Shinya Yamanaka and Sir John Gurdon were jointly awarded the Nobel Prize for Medicine for discovering that it was possible to convert mature cells into stem cells and, in the process, turn their biological clocks back to zero.
However, it also became clear that turning back the clock with transcription factors (known as Yamanaka factors) can cause cell identity to be erased which, in turn, can lead to cancer.
Subsequent research suggested that it should be possible to use different transcription factors to turn back the clock safely and a growing body of evidence has emerged to support this theory.
Now the race is on to find the transcription factors that can safely control biological age. Finding them will unlock the development of new drugs that can be used to treat the most prevalent and pernicious of age-related diseases.
As this prize comes within reach, interest in the field is growing apace. But the scientific challenge is immense. With 1300 transcription factors in every possible combination to consider, finding the optimal combination to control rejuvenation is a formidable task.
To speed up this task, Shift is applying the latest advances in cell simulation models. We are building a platform that combines generative AI models with Aging Clock 2 (AC2) - our high-accuracy, high-throughput biological aging clock. Harnessing these technologies, we can search combinatorial space more than a hundred times faster.
Our platform predicts which sets of genes are most likely to control rejuvenation in particular cells and then allows us to test, improve and validate those predictions.
New gene combinations
Using our predictive driver ML clocks we identify new gene combinations which are likely to be rejuvenating.
Web lab testing
We over-express these genes in different combinations and analyse their effect on cellular gene expression using single-cell transcriptomics.
AC3 age prediction
We compare predicted versus actual rejuvenation using our high-accuracy, high-throughput single cell transcriptomic clock (AC3).
We update our machine learning models of rejuvenation biology and validate their improved predictions using simulated perturbation experiments (e.g. GEARS, scGPT).
Safety and translatability
For the most rejuvenating combinations, we analyse gene expression signatures of cell identity and perform fibroblast functional assays.
The gene combinations which show the greatest efficacy coupled with the least pluripotency are taken forward into therapeutic development.
Novel drug compounds may exert unexpected effects on aging biology. Some novel drug compounds may slow down or even reverse biological aging, opening up new therapeutic opportunities. The Shift platform helps pharma to unveil these effects.
Application 1: Toxicology screening
Screening of collections of drug compounds to detect accelerated aging at the single cell level, for higher sensitivity and resolution.
Application 2: Rejuvenation screening
Screening novel drug compounds to uncover novel disease-modifying drugs with the potential to reduce the biological age of cells.
Application 3: Advanced screening
Screening of collections of genes to uncover novel disease-modifying drug combinations with the potential to reduce the biological age of cells.
Shift has assembled a talented team of research scientists and advisors who are backed by experienced biotech investors.
Daniel has a PhD from the University of Cambridge. His early research focused on the role of mutations in the mitochondrial genome in rare diseases. In 2017 he founded Shift Bioscience. Since then, he has been on a scientific journey from mitochondria through mouse clocks to single-cell clocks for CRISPR screening and, finally, to where Shift is now: pioneering machine learning techniques to predict a safe rejuvenation pathway.
Why? To quote Rick Klausner: “So that we die young, after a very long time.”
We have all the pieces of the puzzle in place. We are now focused on the rigorous application of our processes and techniques to validate and leverage our findings. At the same time, we are making sure we have the operational infrastructure we need to grow the company and keep up with the science.
My role is to be a bridge-builder, to explain what we are doing to the team, investors, collaborators and the outside world.
We are in a race. We are not the only ones who understand the science and its possibilities. At the moment, we think we are ahead – and we want to stay that way.
We don’t imagine it will be a single company that leverages this technology, we think it’s going to be a whole industry. We see our role as enabling that industry, by providing the underlying biology that helps other people address particular disease targets.
It’s a rare privilege to be on this journey. And it’s energising to know that the destination is within our reach.
Brendan has a PhD in pharmacology from the University of Cambridge. The driving force behind Shift’s pioneering use of active machine learning, Brendan leads a team of five scientists, addressing what he describes- with characteristic understatement - as a “big technical challenge”.
Why? Instead of just focusing on one disease, if we can treat five or even ten diseases at the same time, we can have a massive impact on human health.
My research background is in molecular biology but I also have a deep interest in machine learning. It is because we are able to combine such different scientific disciplines at Shift that we have been able to make such good progress.
I lead an amazing team. We are all working incredibly hard and pulling together to achieve a common goal. It’s so rewarding to be part of a team you trust and we all help motivate each other.
If anyone says ‘because that’s the way we’ve always done it’, it sets off alarm bells. Scientifically at Shift, nothing is assumed, everything is tested. As a team, we all appreciate the fact that every single step is scrutinised.
AltumAge, Histone-mark clock inventor
CEO at Aspective, Trigenix (acquired by Qualcomm),
MBA at Wharton.
Tony Kouzarides is Professor of Cancer Biology at University of Cambridge and a group leader at the Gurdon Institute.
CTO LabGenius and AI expert. Honorary Research Fellow UCL
F-Prime invests in healthcare and technology ventures, with $4.5 billion assets under management.
Kindred invests in biotech and technology ventures, with a unique Equitable Capital model
Shift Bioscience received initial seed funding in July 2017 from Jonathan Milner, followed by friends and family investors. This was followed by seed funding from F-Prime and Kindred in February and September 2022.
Would you like to be part of a scientific endeavour with the potential to transform all our lives?
We are always looking to connect with exceptional people to join our mission-focused team and accelerate the ground-breaking science underway on the Cambridge Biomedical Campus, one of the world’s leading centres for life sciences and healthcare R&D.
If you are a talented scientist, working in an area relevant to cell rejuvenation and reprogramming, get in touch to learn about any upcoming opportunities to join the team.
To get in touch with Shift Bioscience, please email firstname.lastname@example.org
Main research site
Shift Bioscience Ltd
The Gurdon Institute
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Shift Bioscience Ltd
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