Richard Bayliss, Professor of Molecular Medicine, is co-leading the Data Driven Multi-scale Engineering of Cell Fate Decisions project.
He’s part of a team in School of Molecular and Cellular Biology that has won a groundbreaking £1.2 million funding award which brings together UK and Japanese universities to undertake cell engineering research which could have a major impact on future cancer treatment.
The £1.2 million funding is awarded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Japan Science and Technology Agency (JST).
It is matched by a similar award to Japanese colleagues, led by Professor Mariko Okada, until recently the director of the renowned Institute for Protein Research at Osaka University, and including scientists from Osaka and Tokyo Universities alongside RIKEN, Japan's largest comprehensive research institute.
The research
Our body’s cells survive and proliferate by sensing and responding to environmental cues through a series of signals that travel through molecular pathways and modify their internal functions. These responses work alongside other signals that are responding to different cues and can be seemingly random.
Until now, understanding of cell signalling and cell fate has focused on tracing these isolated individual pathways, leading to an incomplete understanding of complex cellular regulation that includes multiple signalling pathways and diverse responses to stimuli.
This makes it sometimes difficult to predict how cells will respond to therapeutic drugs that target the signalling processes. As a result, there is a huge burden of drug discovery research that frequently fails to materialise at clinical level. To understand the heterogeneous and unpredictable responses to therapeutics, a holistic approach is needed to grasp the intricate communication networks involved in cell fate.
The Bioengage project will undertake international and interdisciplinary research into creating engineered cells that respond to natural and artificial triggers with a pre-programmed fate determined by a synthetic circuit.
To achieve this, scientists will combine cell biology with systems modelling, de novo protein engineering, novel molecular tools and synthetic circuits. The engineering process will involve data-driven modelling of cell fate pathways, and the design and implementation of synthetic components and circuits.
If successful, they will be able to exert a level of control over what is naturally a random and unpredictable element in cells that causes resistance to current drug treatments.
Research in the Bioengage project will eventually enable researchers to test ideas about how to overcome resistance to treatments at the molecular level and lead to ideas for better treatments that block tumour relapse by forcing cells to respond to drug treatment with a predictable and reproducible outcome.
One of the key approaches underpinning this research was developed by Professor David Baker of the University of Washington Institute for Protein Design, along with Sir Demis Hassabis and Dr John Jumper of Google DeepMind in London, who have jointly been awarded the 2024 Nobel Prize for Chemistry for their work in using AI in designing synthetic proteins and predicting protein structure.
Collaboration at a cellular level
The BBSRC/JST award is significant because it allows top scientists from the UK and Japan to collaborate at a deep and meaningful level. It's very rare for funding to be awarded with a 50:50 international split like this. As well as being internationally collaborative, Bioengage is an interdisciplinary project, combining cell biology – the study of the structure and function of cells; systems biology – understanding how cells work together in the larger picture; and synthetic biology – engineering and modifying existing cell structures.
The funding means academics can assemble the optimal team with the best people at a global level. Seven senior academic scientists from the UK and six from Japan will be supported by early career scientists from the UK and Japan, all of whom will be working in each other’s country and fundamentally embedded in a different academic and research culture.
The UK team comprises structural, cell, chemical and computational biologists who are leading experts in the fields of cell cycle and cell signalling. The University of Leeds contingent includes Richard Bayliss, Professor of Molecular Medicine and John Ladbury, Professor of Mechanistic Biology, alongside Dr Josephina Sampson, a postdoctoral researcher in cell biology who has played a key role in building the UK/Japan relationship with Professor Okada in Osaka.
In addition, the UK team incudes Alexis Barr and Reiko Tanaka from Imperial College; Neil McDonald and Katrin Rittinger from the Francis Crick Institute; and Louise Walport who works at both of these London institutions.
Our Japanese colleagues are widely acknowledged as world-leading synthetic biologists in molecular and cell-to-cell communication, and systems biologists in omics and mathematical modelling. The team includes Mariko Okada, Nobuyasu Koga and Satoshi Toda from Osaka University; Shinya Kuroda and Hirohide Saito from Tokyo University, and Yumi Konagaya from the RIKEN institute.
Impact on future research training and therapeutic approaches
From a longer term point of view, the value of this project in training scientists to collaborate internationally is immense.
We want to excite more scientists to work in this area of biology and to work internationally in the pursuit of solutions to global challenges.
The Bioengage project provides bespoke research training across the international collaboration network to foster the next generation of interdisciplinary scientists and research leaders in biological engineering, who can take their experience into new research groups and fields and develop their own programmes.
The project will also lead to new therapeutic approaches for diseases regulated by signalling and other biological pathways – not only cancer, but ageing, inflammation and diabetes.
