The Rules of Life

Deep in the heart of the West Cambridge site, a project is taking shape that could fundamentally alter our understanding of life itself.

In collaboration with the Department of Chemical Engineering and Biotechnology (CEB) and British Antarctic Survey (BAS), a team of intrepid researchers is embarking on a bold journey to unravel the mysteries of how life adapts and thrives in some of the most extreme environments on Earth – those locked in perpetual sub-zero temperatures.

The ambitious endeavour aims ‘to boldly go where no researcher has gone before’, venturing into the unknown to unlock secrets that could have profound implications for our planet and its future.

The project, dynamic live cell imaging at sub-zero temperatures, has been granted funding by the UKRI cross research council responsive mode pilot scheme, one of just 36 projects (out of nearly 900 applications) to be given the green light in the first round scheme.

It means the research can develop from a provisional stage, with hopes that the creation of microscopes capable of operating at sub-zero temperatures are within touching distance.

A game changing endeavour

The interdisciplinary nature of the project – at the intersection of biology, physics, engineering, and chemistry – ensures that its impact will be felt across multiple fields of study.

By developing a new microscopy platform capable of observing living cells in sub-zero conditions, the Cambridge team is not just advancing our understanding of cold biology; they are unlocking new research possibilities that could lead to breakthroughs in science and technology with far-reaching societal, economic, and environmental benefits.

This pioneering work underscores the importance of continued exploration and innovation in understanding life in all its forms, particularly in environments that challenge our existing knowledge. As the research progresses, the findings are poised to revolutionise our understanding of life at the extremes, opening doors to new scientific frontiers and offering insights that could help address some of the most pressing challenges of our time.

The challenge of understanding life in extreme cold

The study of life’s adaptation to extreme environments pushes the boundaries of our understanding of biological systems, from the molecular level to the whole organism. Nearly 90% of the Earth's habitable environments are below 5°C, including the deep ocean trenches and polar regions–zones where the average human body would quickly succumb to the cold.

Yet, these are precisely the places where a diverse array of life not only survives but flourishes, presenting a tantalising mystery: how do biological systems function in such extreme cold?

Proteins, the molecular workhorses of life, are central to this mystery. Their ability to perform tasks such as catalysing reactions or forming cellular structures depends on their precise three-dimensional shapes. While we have a solid grasp of how proteins behave at higher temperatures, our knowledge of their function at sub-zero temperatures–where they are less stable and more prone to oxidative damage–is sorely lacking.

This gap in understanding is particularly urgent given the current climate crisis and the potential large-scale loss of these cold environments, along with the unique forms of life they support.

Researcher in white lab coat pipettes liquid into sample box

Anne-Pia works on frozen cells

Three people sit side by side at cluttered work desks

Francesca (CEB), Edward (CEB) and Anne-Pia (BAS/CEB) at their work stations in CEB

This microscope has been altered to allow the team to observe frozen cells, with ice crystals forming.

Researcher in white lab coat and green gloves operates joystick while monitoring two computer screens

Francesca observes a sample using the sort of laser microscope the team are looking to develop into one capable of operating at sub-zero temperatures

Bridging the knowledge gap

To address this critical knowledge gap, the team at Cambridge is focusing on the in-situ operation of proteins within living cells at temperatures around 0°C and below.

Understanding protein function in these conditions is no easy task, as proteins are highly sensitive to temperature, and their behaviour is influenced by the crowded cellular environment in which they exist. Adding to the complexity, there are currently no imaging tools specifically designed for studying live cells at such low temperatures.

This project aims to fill that technological gap by developing an automated microscope system optimised for high-resolution optical imaging of live cells from Antarctic species at sub-zero temperatures. By leveraging cutting-edge technologies such as high-speed lightsheet and structured illumination microscopy, the researchers plan to observe protein folding and function within cells under conditions that mimic their natural, frigid habitats.

This interdisciplinary effort–drawing on expertise in ecology, cellular biology, and engineering–promises to transform our understanding of how proteins behave in the cold, opening up new avenues in the field of cold biology research.

Pioneering technologies for uncharted territory

The success of this project hinges on recent technological advancements. For instance, the genome sequencing of the Antarctic fish Harpagifer antarcticus, the model species for this study, provides critical genetic insights that were previously unattainable. Alongside this, innovations in cell culture techniques for Antarctic species, combined with breakthroughs in microscopy and data analysis through deep neural networks, have set the stage for a new era in biological research.

By adapting advanced imaging tools to work with Antarctic species, the researchers are not only pioneering new ways to study cellular biology but also creating technologies that could be applied in other extreme environments. These advancements have the potential to extend beyond the lab, influencing fields as diverse as cryopreservation, organ transplant, and even the development of therapies for diseases associated with protein misfolding, such as Parkinson’s and Alzheimer’s.

Addressing the climate crisis and biodiversity loss

One of the most pressing reasons to undertake this research is the urgent need to address the knowledge gap surrounding life in cold environments, especially given the accelerating impacts of climate change. The polar regions and other cold habitats are experiencing some of the most dramatic changes, with rising temperatures threatening to disrupt ecosystems that have evolved over millions of years. As these environments warm, the unique species adapted to thrive in the cold face unprecedented challenges, and in many cases, extinction.

Understanding how these organisms function at a molecular level is crucial not only for preserving biodiversity but also for gaining insights into how life might adapt–or fail to adapt–to rapidly changing conditions. This knowledge is vital as we work to mitigate the effects of climate change and preserve the ecological balance in these fragile environments. Moreover, the principles uncovered in this research could inform broader conservation strategies and help guide efforts to protect other vulnerable ecosystems around the world.

Credit: BAS

The broader societal benefits of cold biology: What could this all mean for our future?

The implications of this research extend far beyond the Antarctic. By understanding how proteins and other biomolecules behave in the cold, we can improve our ability to store biological materials at low temperatures, which is crucial for applications ranging from vaccine preservation to organ transportation. Moreover, the insights gained could lead to the engineering of proteins and enzymes with optimised performance at lower temperatures, benefiting various biotechnological applications.

This project also offers a unique opportunity to explore how evolutionary pressures shape life in extreme environments. The lessons learned from cold-adapted organisms could inform our understanding of life’s resilience, shedding light on the fundamental principles that govern biological systems across a range of conditions. These insights are invaluable as we face the twin challenges of climate change and biodiversity loss, which threaten not only the coldest regions of our planet but also the species uniquely adapted to survive there.

Watch our video, in collaboration with the British Antarctic Survey, about the project: