Cell-to-cell communication discovery unlocks new potential

Our School’s Dr Enrico Ferrari and an international team of scientists have discovered that ‘size matters’ in cell-to-cell communication. When it comes to the mechanisms that cells use to communicate with each other, cell size really does matter, according to pioneering new nanobiotechnology research which has important implications for the diagnosis and treatment of disease.

This research has been to advance the understanding of ‘exosomes’ – tiny biological structures (or ‘vesicles’) which are used by cells in the body to transfer information. The researchers believe the findings could be significant for several fields of medical science, from personalising medical treatments to better understanding the growth and spread of cancerous tumours.

Exosomes are packed with proteins and RNA. They can be generated by one cell, taken up by another, and trigger a specific response. To date, scientific research has focused on the content of exosomes, but a new study led by scientists at the University of Lincoln, UK, focused instead on the size of exosomes and how this affects the way they work.

Dr Ferrari (centre)
Dr Ferrari (centre)

Led by Dr Enrico Ferrari, a specialist in nanobiotechnology, the team discovered that the smaller the exosomes are, the easier it is for target cells to pick them up. This makes communication between cells much faster. The study examined exosomes taken from a patient with a high-grade glioma (rapidly growing brain tumour). The researchers had previously found that some stem cells within the patient’s brain were producing exosomes that were responsible for supporting cancer cells and making them more aggressive.

Their latest work suggests that the level of aggression in a tumour could be determined by the size of the exosomes produced by the cancerous cells – for example the smaller the exosomes, the faster the cells can communicate and reproduce, and the quicker the cancer develops.

These initial findings could therefore have important implications for the prognosis of different cancers in the future, as doctors may be able to examine the size of the exosomes produced and more accurately predict the course of a patient’s tumour. The study was carried out by researchers from our School of Life Sciences, the Department of Medical and Biological Sciences at the University of Udine, and the Department of Neuroscience at Santa Maria della Misericordia University Hospital, both in Italy. The findings are published in the scientific journal, Nanomedicine: Nanotechnology, Biology and Medicine.

“Rather than looking inside the exosome, we decided to take a detailed look at the nature of the vehicle, specifically its size”, explained Dr Ferrari. “If you think of an exosome as a package, regardless of the specific molecules it carries, the nature of the ‘envelope’ is likely to be of great importance to the delivery of the message. The larger the envelope, the more difficult it is to deliver!

“Previous research has examined how size affects the behaviour of artificial nanoparticles in a human body, and this new study found that biological particles like exosomes may act in much the same way – the smaller they are, the ‘louder’ their message is, as it is easier for target cells to take them up and ‘hear’ the message.

“Traditionally it has been difficult to observe this behaviour in exosomes because they are extremely small (well below optical resolution), very elusive, and difficult to isolate. However, our team developed a new set of techniques to overcome all of these factors and answer important questions about size-dependent uptake, which previously have not been addressed.

“The size of different exosomes has been explored in a few other studies, but never in relation to how effectively they can deliver their messages.”

The new research could also have future implications for the delivery of medicine, as exosomes could potentially be used as nanocarriers for specific drugs. The scientists predict that it may be possible to manipulate the size of exosomes used in therapeutics to make them more effective, and to use the personalised exosomes produced in the human body – or particles which mimic the way they behave – to achieve more targeted and efficient drug delivery. This process is called exotherapy.

The team now hopes to pursue further research in this area to more accurately understand the impact of exosome size on the way that cells communicate, and develop ways this knowledge can be used in the diagnosis, prognosis and treatment of individual patients. The research paper detailing the team’s findings in full, entitled Size-dependent cellular uptake of exosomes, will feature in the April issue of Nanomedicine: Nanotechnology, Biology and Medicine and is available to read online.

New professor at forefront of microbial research

The lead academic in a major research project which aims to improve our understanding of how microorganisms survive has joined the University of Lincoln, UK.

Stuart Humphries, Professor in Evolutionary Bio-Physics, will be a senior academic figure within the School of Life Sciences’ Evolution and Ecology research group.

Professor Humphries was awarded £941,132 from the Leverhulme Trust in 2012 to investigate the influence of cell shape on ecology.

It is hoped the results of this five-year project will lay the foundations for future advances in fields such microbial ecology, biosecurity, medical microbiology and ocean ecosystem dynamics.

Professor Humphries said: “Despite the importance of microbes, such as bacteria and fungi, to our health, culture, agriculture and industrial processes we still have no real idea of why microorganisms look the way they do. An example is that cells in our immune system seem to respond to differently shaped microbes and bacteria. If we can find out how this happens it could eventually assist with medical diagnostics.”

At microscopic scales, organisms are largely freed from the limitations set by physical processes. This release from physical constraints means that for microorganisms other forces must have driven the evolution of their shape. Therefore scientists are beginning to think differently about how microbes interact with the physical world.

This research will provide a clear understanding of the links between microbial shape and function that will change our outlook on how and why microorganisms survive and flourish.

Professor Humphries’ main interests are the way in which physics and engineering can be used to understand biological processes.

He said: “All life evolves and changes in response to various pressures. My interests span from dinosaurs all the way through to coral reefs and back down to bacteria. The laws of physics are constant so will always apply to all of these organisms.

“I’m interested in how physics constrains evolution and how organisms can take advantage of physics to improve their chances of leaving descendants. Microbes are particularly important to our health, culture and industry and Biophysics – which uses methods of, and theories from, physics to study biological systems – will allow us to understand how these organisms work.”

On his appointment at the University of Lincoln, Professor Humphries added: “I was struck by the fact everybody at Lincoln seems to have the same overarching vision. There is a real opportunity to create something special here.”

Measuring and understanding mood in animals

Dr Oliver Burman with Riley
Dr Oliver Burman with Riley

As our knowledge of animal behaviour and cognition grows, we are becoming more effective at assessing animal welfare.

Dr Oliver Burman, Senior Lecturer in the School of Life Sciences, was recently awarded a substantial grant from the Biotechnology and Biological Sciences Research Council to develop a new approach that will advance understanding in the field, particularly in respect to how we measure the moods and emotions of animals.Dr Burman is examining how animals respond to unexpected changes in the quality or quantity of rewards. Through this research, Dr Burman hopes to demonstrate that the way in which animals respond to unexpected changes can be influenced by their affective state, with animals with a more ‘positive outlook’ being faster to recover from surprising decreases in reward quantity.

The project is funded for three years, with a research team lead by Dr Burman including a post-doctoral research fellow (Dr Sarah Ellis) and a research technician.

Exciting Revamp of Life Sciences Courses

Students starting life science courses in September, such as biology, biomedical and forensic science, and animal programmes will benefit from an exciting revalidation of their degree programmes.

The new School of Life Sciences was formed in January; bringing together two Schools which had previously focused separately on natural and applied (human) sciences, and biological sciences.

As animal behaviourists and biologists join forces with specialists in chemistry and forensic anthropology, incoming students will be able to benefit from a wider range of optional modules to reflect the breadth of expertise within the School, and learn about areas of science which they otherwise might not have the opportunity to study on their chosen course.

The changes to the Life Sciences programmes were commended during the revalidation process for their involvement in ‘Student as Producer’ as students are offered opportunities for practical engagement with research-active staff. An example of this is the Undergraduate Research Opportunities Scheme, which enabled 1st year students on the BSc (Hons) Biomedical Science to work with a world renowned cancer biochemist within the School to produce a poster at a UK scientific conference and a journal manuscript with undergraduate student authors.

Head of School, Dr Libby John, said: “We are very excited about the changes to our courses. We have a lot of expertise within our School, and are using it to provide all our students with the best advantage. We think giving students the opportunity to choose from a wider range of modules, and the responsibility to be fully engaged in research within the School, provides them with a real opportunity to enter the world of employment with a truly unique, and relevant, degree.”

In addition to the improvements to the Life Sciences courses, the majority of teaching on Bioveterinary Science and Animal Behaviour and Welfare programmes will, from September, be delivered at the Brayford campus, to enable students to benefit from the state-of-the-art science facilities on site. Specialist animal facilities will continue to be available at the Riseholme campus, 4 miles from the main city centre campus.

Changes to courses are subject to final approval.

www.lincoln.ac.uk/lifesciences