Taking a closer look at life
A team at Cambridge is helping to drive biological discovery through innovation in microscope technologies
When light is confined to a really tiny space, it starts exerting a physical force on the object it’s directed at. This weird property is the basis of a microscope technology called ‘optical tweezers’, which uses light to pull on cell membranes and assess their strength under different conditions.
Dr Lisa-Maria Needham, a self-confessed technophile, enthusiastically describes a custom-built microscope incorporating optical tweezers and other advanced light-based tools, pioneered by her predecessor Dr Kevin O'Holleran: “‘The photo-manipulation suite is my favourite microscope, it’s a bit like a Swiss army knife! It can manipulate biological samples in so many precise ways, helping researchers gain deeper insights into biological processes, diseases, and drug pathways.”
Needham leads a team that’s unifying the microscope facilities spread across seven of the University’s biological sciences departments and providing everything researchers need to run their experiments. The Microscopy Bioscience Platform incorporates electron and light microscopy, image analysis and data management.
Most excitingly for Needham, it also includes a research arm focused on technology innovation.
“We’re in a unique position here of being surrounded by amazing biological research. The thing I love most about developing new microscopes is collaborating with the biologists to create technology with real-world applications in mind," she says.
Since the platform, based in the School of Biological Sciences, was launched in November 2024 Needham has put a huge amount of effort into promoting its benefits: essentially, that advanced microscope technologies can advance the frontiers of scientific discovery.
Dr Lisa-Maria Needham. Image: Jacqueline Garget
Dr Lisa-Maria Needham. Image: Jacqueline Garget
"We’re developing microscopes that don’t exist anywhere in the world.”
“I believe that advances in technology go hand in hand with biological discovery,” she says. “Scientists get to a certain point in their research where they know there’s something going on, but nothing exists to help them see it. That's driving technological innovation.”
Here is some of the ground-breaking research supported by Needham's team and other facilities in the University's School of Biological Sciences.
How do bodies develop?
Dr Ben Steventon’s team studies developmental biology - how animals develop from a single cell into a complete organism. He wants to understand how cells decide what they’re going to become - like skin, muscle, or brain - and how these choices happen at the right time and place in development.
The team uses zebrafish and chicken embryos, and mouse embryonic stem cells - which can turn into any type of cell - to work out how single cells respond to important signals that generate a well-proportioned body plan.
Using live 3D time-lapse microscopy, the team can now actually watch cell fate decision events and cellular rearrangements as they happen.
This is important for understanding how the normal processes of development go wrong to cause developmental defects in humans. In addition, many of the dynamic processes that drive cell movements in the embryo are the same mechanisms that cancer cells use when they invade the body.
"Advanced microscopes allow us to set up time-lapse experiments over several hours or even days without damaging the embryo. This has enabled us to capture in real-time what cells do as they invade and migrate to different parts of the embryo."
Dr Ben Steventon, Department of Genetics
This image shows chicken embryos at 24h, 30h and 38h of development, stained with fluorescent dyes to show when different genes are switched on in the developing nervous system. The forebrain (in magenta) develops first, then the hindbrain (in green) and spinal cord (in red). Image: Alexandra Neaverson.
The central 3D image is the growing tip of a zebrafish embryo’s tail, showing individual cells. The coloured images around this show groups of cells in which different genes are activated, which determines the ability of the cells to generate different types of tissue. The tail tip was imaged using a laser scanning confocal microscope. Image: Dillan Saunders.
How do cells turn cancerous?
Dr Fengtong Ji, in the lab of Dr Fengzhu Xiong, is uncovering the secrets of how nature builds life – and he’s using nanorobots to do it. He wants to understand how to keep cells ‘happy’, which can help find new ways to treat disease and support cell regeneration.
“I’m developing nanorobots that can live inside embryos, and these are helping me to gain new insights into how body tissues develop.”
Dr Fengtong Ji, Gurdon Institute
Complex living creatures develop from tiny embryos - but how? The answer lies in the dynamic behaviours of cells as they move, grow, and decide their fate during development. In this incredible journey, the environment around each cell plays a crucial role in instructing it where to go and what to become.To understand this environment, the team uses tiny nanorobots as friendly companions that travel alongside cells, and relay what the cells might be experiencing.
By listening to this cellular ‘conversation’, the team can learn how life forms take shape - and why cells sometimes go wrong and become cancerous.
This image reveals cells (blue) growing with tiny nanorobots (red dots). The nanorobots organise into a pattern as the cells move, which reveals the tissue mechanics in a developing chicken embryo’s tail. Spinning disk confocal microscopy image: Dr Fengtong Ji.
How can we protect coral reefs?
Dr Susie McLaren, also in Dr Fengzhu Xiong's lab, is exploring how corals and sea anemones form partnerships with algae - a relationship essential for the health of coral reefs.
These marine animals, known as cnidarians, begin life as tiny balls of cells and gradually develop into adult forms with tentacles and a mouth. The team is studying how the cnidarians’ symbiotic relationship with algae is established during this transformation.
Using a combination of microscopy, computational approaches and experiments, they’re also investigating how the breakdown of this symbiosis, which leads to coral bleaching, alters the host’s behaviour and ability to survive. The team is developing new approaches that allow them to predict the response of this symbiosis to environmental stress.
"We want to understand how the coral reef-sustaining symbiosis between cnidarians and algae is built, and why it breaks down under environmental change. Our goal is to discover new biology and contribute to efforts to conserve and recover marine ecosystems."
Dr Susie McLaren, Gurdon Institute.
This is a developing sea anemone with spherical algae living inside its cells. The tentacles face upwards towards the light and the algae produce nutrients from photosynthesis, transferring some of these nutrients to their host. Confocal microscopy image: Dr Susie McLaren and Alex Sutherland.
How and why are there so many different species?
Dr Emilia Santos and her team are exploring how biodiversity develops and changes over time, using tropical cichlid fish.
Lake Malawi is home to hundreds of closely related species of cichlid, all of which evolved from a single ancestor. They vary widely in how they look, what they eat, and how they behave and interact.
The team wants to know what allowed these fish to diversify so dramatically and rapidly. They study embryonic and adult life stages, using a combination of genetics, imaging and behavioural studies.
"Cichlid fish offer a rare window into the processes of evolution in action. By understanding how they adapt and evolve, we can gain important insights into how other animals - including humans - can adapt, survive and diversify.
"This is especially relevant today, as climate change and habitat loss threaten species across the globe."
Dr Aleksandra Marconi, Cichlid Eco-Evo-Devo lab, Department of Zoology
Learning from one of the most astonishing examples of biodiversity can help to better understand, and potentially help protect, the rich variety of life in our changing world.
Santos' team is studying special pigment patterns called egg-spots - bright markings found on the anal fins of many male cichlids. These are important for attracting mates and vary widely in size, number, and position, both between and within species. The yellow reveals a gene the team is looking at. By studying where and when certain genes are switched on, they hope to understand how the striking patterns develop and evolve. Image: Dr Aleksandra Marconi.
In this cichlid embryo about two days after fertilisation, basic outlines of major structures like the brain and eyes are already visible. The team studies the cells in pink, from a group called the 'neural crest', which move throughout the embryo and later develop into a wide range of adult features including skin pigment patterns and facial structures. Since these traits vary greatly between cichlid species, studying how the neural crest works helps the team understand the origins of their incredible diversity. Image: Dr Aleksandra Marconi.
Are there better treatments for pancreatic cancer?
Professor Laura Machesky’s team is looking for new ways to block the spread of cancer cells, which could ultimately improve treatment for pancreatic cancer patients.
The team studies how pancreatic cancer cells adapt to the harsh conditions inside tumours - including low oxygen, scarce nutrients, and disrupted tissue structure - to drive tumour aggressiveness and spread. Adaptations serve as protective defence mechanisms, allowing the cancer cells to evade the body’s immune system and making chemoradiotherapy ineffective.
"Cambridge’s core light microscopy facilities are allowing us to gain new insights into how pancreatic cancer cells operate – so that we can find ways to disrupt them."
Professor Laura Machesky, Department of Biochemistry
The team's focus is on how cancer cells change their internal structure and metabolism to help them move through the tumour environment, absorb nutrients, and how they generate energy to power this movement. They've found that pancreatic cancer cells use creatine as an alternative energy source. They’re now investigating when this pathway is activated, and whether it could be targeted for therapy.
These fluorescent images show human pancreatic cancer cells that have eaten and internalised the sugar molecule dextran (green). DNA in the cancer cells appears blue. Zooming in (right image) reveals that dextran is localised inside cellular structures called lysosomes, which contain digestive enzymes to transform the sugar into simple molecules used by cancer cells to support their survival. Images: Dr Roberta Palmulli.
On the left are normal pancreatic cancer cells - the cell skeleton is green, focal adhesions (which stick cells to the underlying surface) are coloured in magenta, and DNA is blue. On the right are pancreatic cancer cells that have been genetically engineered so they can't use creatine metabolism to move and invade. Images: Dr Lisa Dobson.
Needham’s team at the Microscopy Bioscience Platform provides training, advises researchers on different approaches and techniques using a wide range of microscopes, and plays a key role in experimental design.
She is campaigning to get equal recognition to scientists for their results too.
“Technical staff are often not as highly regarded as the researchers, but we’re all scientists,” she says. “I have an amazing, intelligent, creative team of people who love tech and they’re enabling science that wouldn’t otherwise happen. So it’s really important for us to get fair attribution – not only as a way to measure our impact, but also because it helps our grant applications to get more equipment in the future.”
Needham wants the platform to become a hub for collaboration, allowing researchers to connect with others across the University and beyond to advance their work. Some of the technologies developed here have already been transferred to commercial use, through spin-out companies and industrial collaboration. She says:
“Any time any microscopy work is needed I want people to come to us - even if they’ve just got a vague idea of what they want to do, even if they’ve never used advanced microscopes before - we can help.”
Published: 25 June 2025
For more information about the Microscopy Bioscience Platform, contact Lisa-Maria Needham in the Department of Physiology, Development and Neuroscience.
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
