Winners of £50K Franklin research residencies announced

Three of the UK’s brightest life science companies have been awarded research prizes by the Rosalind Franklin Institute in collaboration with the Science and Technology Facilities Council (STFC), a part of UKRI. These research prizes will enable the winners to benefit from the Franklin’s top-level technologies and support to move their work forward.

Winning biotech companies Neuro-Bio, Oxford Target Therapeutics and Hypha Discovery will each spend a residency of 12 weeks at the Rosalind Franklin Institute, allowing them to investigate, respectively, a potential early diagnostic test for Alzheimer’s disease, a promising therapy for Triple Negative Breast Cancer, and new technologies for determining the chemical structures of small drug metabolites.

Oxford Target Therapeutics plans to use the Franklin’s serial focused ion beam scanning electron microscopy to find out for the first time exactly how its treatment acts on a micromolecular level on both breast cancer cells and healthy cells.  Victor Bolanos-Garcia, Founder and Chief Scientific Officer, said: “Without this opportunity, we wouldn’t be able to fund the cost of this work ourselves as we have too many competing priorities. But it is instrumental for us, so the Franklin’s offer of funding and expertise will really fill a vital gap.” The results of the research will help the company plan more effective strategies to treat Triple Negative Breast Cancer, one of the most aggressive and deadly forms of the disease. 

Neuro-Bio aims to measure how a peptide biomarker that may indicate pre-symptomatic Alzheimer’s Disease can be accurately detected from saliva samples. The company will use the Franklin’s liquid chromatography-mass spectrometry (LC-MS) technology to analyse the biomarker, known as T-14. The project will allow them to see how the amounts of the peptide biomarker in saliva correspond to the different stages of the disease, by analysing hundreds of samples donated by patients living with Alzheimer’s.  Sara Garcia Rates, Chief Scientific Officer of Neuro-Bio, said: “We’ve previously done a very limited  pilot study in-house, but this work with the Franklin will allow us to validate the test, greatly increase our throughput and enable the quantification of T14. This transformational step will enable us to progress from a very lab-based project into something that doctors will be able to access, very much faster than we’d have been able to do otherwise.” 

Professor Ben Davis, Interim Director of the Rosalind Franklin Institute, said: “The Franklin is tasked with creating advances which push forward life science. The creative challenges posed by these SMEs are a great testbed for our technologies – this creates a golden opportunity to explore new areas together and so provide the companies with the leaps in results they need to take their products to the next stage.”

The Franklin is the national institute developing disruptive new technologies designed to tackle major challenges in health and life sciences. Their inaugural SME (small and medium enterprise) competition aimed to make these technologies – and the expertise of the Franklin’s own scientists – available to smaller life science companies in the UK, to help them overcome a specific research challenge. The residency prizes, which include bench space, consumables and instrument time, are valued at between £30,000-£50,000. All intellectual property generated during the residency will remain with the individual companies.

The UKRI-STFC part funded the awards. Dr Barbara Ghinelli, Director, Innovation Clusters and Harwell Campus, UKRI-STFC, said:  “We are delighted to support this programme at the Rosalind Franklin Institute, a core partner within the Health Tech Cluster at Harwell. Fostering collaboration and partnerships between world leading institutes and innovative businesses helps to drive forward science and innovation that will have a real impact. These exciting projects at the Franklin will nurture the development of tools and technologies in business that will have far-reaching impacts on people’s health and wellbeing in the UK and around the world.”

Left-handers aren’t better spatially, gaming research proves

It’s been debated for decades, but now researchers at the University of York and University College London have demonstrated conclusively that left-handedness is not linked to better spatial skills.

By asking participants to download and play a videogame that captured user information and tracked navigational challenges, researchers were able to measure demographic data – including hand preference - and activity from 422,772 international participants, across 41 different countries. They found that left handers were neither better nor worse than right handers at the tasks, clarifying a long-running debate about the links between handedness and spatial skills.

The brain has two hemispheres, controlling the opposite sides of the body; so in right handers, the left hemisphere controls the dominant right hand, whereas the situation is reversed in left-handers. Many cognitive abilities are also dominated by one of the two brain hemispheres, while right and left handers also show different patterns of lateralisation – the specialisation of a particular area. As a result, many debates about cognitive differences related to handedness are also debates about the effects of brain lateralisation on cognitive abilities.

Spatial cognition, the ability of humans to perceive and navigate our physical environment, is a fundamental set of brain-based skills.  It is also not clearly dominated by either hemisphere, leaving scientists unclear as to whether it has any link to handedness.

Some, inconclusive, research has suggested that left-handers might be better at navigating virtual and real games and left-handed athletes are known to be over-represented in the in professional sports requiring rapid and accurate responses. However, it’s been a tricky issue to research, partly because handedness prevalence changes from culture to culture, and partly because testing for handedness effects requires a large number of participants. Using the videogame Sea Hero Quest, the researchers were able to overcome both challenges.

Dr Pablo Fernandez-Velasco, a researcher at the Department of Philosophy at the University of York, who co-led the study, said: “Recruiting participants in our study through a videogame is a new approach, which allowed us to standardise a test across a very large sample. We found no reliable evidence for any difference in spatial ability between left and right handers, across all countries. Moreover, that large data sample allowed us to confirm that factors like age, gender and education don’t play a part in the relationship between hand preference and spatial ability.”

The users in the study downloaded and played Sea Hero Quest, a free app that measures spatial navigational ability and was originally designed to contribute to research on dementia. It asks participants to view a map featuring both their current position and their goal locations, and they are then asked to navigate a boat as quickly as possible towards goal locations in a specified order. Only participants reaching level 11 of the game were included. Informed in-app consent was obtained from all participants.

Left handers in the sample made up an average of 9.94% of the participants, with more males using their left hand compared with women, similar to what had previously been found in the general population.

Dr Fernandez-Velasco adds: “We’re still finding out so much about cognition, and although we’ve shown that large-scale spatial skills aren’t affected by left and right handedness, perhaps further research will find some differences based on handedness when it comes to navigation styles, or to preferences for different types of environments.”

Benchtop NMR spectroscopy can accurately analyse pyrolysis oils

A team of researchers at Aston University has demonstrated that benchtop spectrometers are capable of analysing pyrolysis bio-oils just as well as far more expensive, high-field spectrometers.

Bio-oils resulting from the intense heating (pyrolysis) of industrial or agricultural by-products, are increasingly seen as potential alternatives to fossil fuels. But the stability and consequent treatment of these bio-oils depends entirely on their composition; and since they are often mixtures of many dozens, or hundreds, of different compounds, analysing such complex mixtures is not simple – or cheap.

Dr Robert Evans, Senior Lecturer in Physical Chemistry at Aston University, explains: “The composition of any pyrolysis bio-oil is absolutely key to future use. For example if there are oxygen-containing chemicals in the oil, that will make the oil more corrosive and it will be more unstable. So in particular we need to know if carbonyl groups are present – where oxygen and carbon atoms are bonded together – as these can have a major impact.”

A leading method of analysis is high-field nuclear magnetic resonance (NMR) spectroscopy, which gives a detailed breakdown of the identity and concentration of chemical species present in any sample. However these large high-field NMR spectrometry machines cost in the range of £600,000-£10million and require a supply of expensive cryogens and solvents, so are generally only found in the very biggest research facilities.

The team at Aston, led by Dr Evans, set out to see if ‘low-field’, or benchtop, NMR spectrometers, could analyse pyrolysis oils well enough to produce the necessary detailed information. Benchtop NMR spectrometers use permanent magnets, which don’t require cryogenic cooling, so cost much less to purchase and maintain. However, using lower strength magnets comes at the cost of lower sensitivity and poorer resolution. While they can find some use as research instruments, they are also commonly found in teaching laboratories.

The study, carried out with collaborators at the University of Tennessee, tested pyrolysis oils produced from a number of different plants, and compared the results from benchtop spectrometers to both high-field spectrometers and other methods of analysis. They found that the benchtop machine estimates compared favourably with titration analysis for overall carbonyl content, as well as matching high-field spectrometry for the specific identification of carbonyl groups such as ketones, aldehydes and quinones.

Dr Evans said: “Despite the known limitations of benchtop spectrometers, a very similar quality of NMR data could be obtained for these samples, enough to accurately estimate concentrations of different classes of carbonyl-containing species. Using benchtop spectrometers will make NMR analysis of pyrolysis oils much simpler, cheaper, and more accessible to a wider range of different users.”

Quantitative Low-Field 19F NMR Analysis of Carbonyl Groups in Pyrolysis Oils is published online today in ChemSusChem, a journal of Chemistry Europe.

World’s first picture of the molecular machinery that makes cilia beat

The first picture of the structures that power human cilia – the tiny, hairlike projections that line our airways – has been produced by a team involving UCL researchers. The information revealed could lead to much-needed treatments for people with rare cilial diseases.

The study, published in Nature on, combined advanced microscopy and artificial intelligence techniques to create a detailed snapshot of the structure of human cilia. These are the microscopic projections on the cells that line our lungs, ears and sinuses and beat rhythmically to keep the lungs clear from mucus and bacteria. People who inherit the rare condition primary ciliary dyskinesia (PCD) have defective cilia that can’t effectively remove debris from the airways, and so suffer from breathing difficulties and chronic lung infections.

For the first time, the scientists visualised the molecular ‘nano-machinery’ that causes cilia to beat, visible as identical structures dotted every 96 nanometres along the cilia length. These structures come together to form the axoneme. In healthy airways, this complex structure is tightly controlled, with molecules precisely arranged to make cilia beat in a rhythmic, wave-like motion, around a million times a day.

In people with PCD, the team found that cilia don’t beat correctly because key elements of the axoneme structure are missing, caused by genetic mutations. This new information could lead to new medicines that target these defects, making cilia beat properly.

Study co-author, Professor Hannah Mitchison (UCL Great Ormond Street Institute of Child Health), said: “Treatments for PCD currently work to clear people’s airways and prevent infection. Our findings offer the possibility of molecular medicines to precisely target tiny defects in the axoneme and make cilia beat as they should.

“Molecular medicines are showing promise for other rare diseases, and COVID-19 research has unlocked new ways to deliver these drugs directly to the lung. If we can combine these advances with our new findings, my hope is that we’ll bring molecular medicines to people with PCD within the next 5 to 10 years.”

The team’s research could also prove useful for infertility, as sperm cells rely on a similar axoneme structure in their tails to propel themselves forward.

The research team was a global collaboration, with scientists based across the UK, US, Netherlands, China and Egypt. “It can be difficult to study rare diseases like PCD, because patients are spread thinly across the world. In the UK, we think around 9,000 families may be affected by PCD,” said Professor Mitchison. “Our study was made possible by a fantastic international collaboration between clinical scientists, biologists and members of the rare disease community willing to take part in our research.”

In addition to human cilia, the team examined the axoneme structure of a single-celled alga called Chlamydomonas reinhardtii, which uses two tail-like projections on its surface to swim. Despite being separated by more than 1 billion years of evolution, the alga’s tails shared structural similarities with the human airway cilia, highlighting the importance of the axoneme throughout evolution.

This study involved collaborators at Harvard Medical School, Alexandria University, University of Leicester, Amsterdam University Medical Centers, Guy’s and St Thomas’ NHS Foundation Trust and Imperial College London.

At UCL, the study was supported by NIHR Great Ormond Street Hospital Biomedical Research Centre, the Ministry of Higher Education in Egypt and a MRC UCL Confidence in Concept grant.

New glass sensors could make commercial nuclear fusion viable

A new generation of durable sensors capable of monitoring commercial nuclear fusion reactors in real time is being developed by UK researchers.

The team, led by Bangor University in partnership with Sheffield Hallam University, plan to identify whether glass sensors developed in 1960s could function in the extreme conditions of a nuclear fusion reaction. If not, the researchers will design and develop new glass sensors.

In December 2022, researchers in the United States for the first time generated more energy from a nuclear fusion reaction than was put in, opening up the possibility that the technology could be both commercially viable, and able to supply abundant, clean energy. But one of the requirements to move from experimental reactions to commercial power generation is reliable monitoring. This means overcoming the extreme conditions created in a fusion reaction: temperatures of 150-200 million degrees Centigrade and highly energetic fast-moving neutrons.

One way of monitoring a fusion reaction is to count the number of neutrons it gives off using scintillators – blocks of material in which a sparkle of light is created each time it is hit by a neutron. By counting the flashes of light, it’s possible to calculate the number of neutrons and the amount of energy being produced – helping to ensure everything is working as intended.

However, existing scintillators are mostly made from either crystal or polymer, which are either difficult to make and limited in size and shape, or lack the durability to withstand the more extreme conditions created by fusion reactions. The sensors currently used to calculate the energy output from fusion reactions tend to be cumbersome and awkward, and do not allow real-time and long term monitoring of the fusion process. For commercial nuclear fusion reactors to be run safely and efficiently, sensors will need to work reliably for years.

Dr Michael Rushton from Bangor University’s Nuclear Futures Institute is leading the new project. He said: “Glass has intrinsic radiation tolerance, so can survive well in very harsh conditions. It also has the advantage that it can be made in very different shapes, from fibres to plates which means sensors can be made for a range of situations within a reactor. And it’s fairly low cost to manufacture. We also hope to be able to ‘tune’ the sensors to work with different types of radioactive particle, so they may also be used for other applications, such as airport or medical scanners.”

Glass sensors able to register radioactive particles were first developed in the 1960s, but they only work if particles are travelling relatively slowly. The Bangor University team is initially seeing if particles emanating from a fusion reaction could be slowed down sufficiently to allow these sensors to work based on their existing composition. If this isn’t possible, then they will use machine learning approaches to identify new configurations of glass that could be effective in the conditions found within nuclear fusion. The new sensor designs will then by manufactured by their colleagues at Sheffield Hallam University.

Professor Paul Bingham from Sheffield Hallam University said: “This research will develop an entirely new range of glass-based sensors for some of the most extreme environments on Earth. This means it could not only help accelerate safe development and deployment of fusion energy technologies, but also have wide-ranging applications in other fields in the future.”

The two-year research project is funded through UK Research and Innovation’s Engineering and Physical Sciences Research Council. It involves Bangor and Sheffield Hallam Universities, the University of Birmingham, the ISIS Neutron and Muon Source at the Science and Technology Facilities Council (STFC) Rutherford Appleton Laboratory as well as a number of commercial partners.

Urine gene test can predict bladder cancer years before diagnosis

Testing for genetic mutations in urine can detect bladder cancer years before the disease shows clinical symptoms, new research has shown.

The study, by researchers from France, Iran and the United States, identified mutations across ten genes that were able to predict the most common type of bladder cancer up to 12 years in advance of diagnosis.

The findings are presented today at the European Association of Urology (EAU) annual Congress in Milan.

Bladder cancer is not a rare disease – it is one of the top ten most common cancers in the UK and the fifth most common in the European Union, with over 200,000 cases in the EU each year. Only around half of those diagnosed with the advanced disease will survive more than five years, mainly due to late diagnosis and recurrence of the disease. By contrast, if their cancer is detected at early stage, more than 80% of patients survive for at least five years.

Lead researcher Dr Florence Le Calvez-Kelm, from the International Agency for Research on Cancer (IARC) in Lyon, said: “Diagnosis of bladder cancer relies on expensive and invasive procedures such as cystoscopy, which involves inserting a camera into the bladder. Having a simpler urine test that could accurately diagnose and even predict the likelihood of cancer years in advance could help to spot more cancers at an early stage and avoid unnecessary cystoscopies in healthy patients.”

The study was based on the UroAmp test, a general urine test that identifies mutations in 60 genes, developed by the Oregon Health Science University spin out company, Convergent Genomics. Drawing on previous research to identify genetic mutations linked to bladder cancer, the research team narrowed the new test down to focus on mutations within just ten genes.

Working with colleagues from the Tehran University of Medical Sciences in Iran, they trialled the potential new test using samples from the Golestan Cohort Study, which has tracked the health of more than 50,000 participants over ten years, all of whom provided urine samples at recruitment. Forty people within the study developed bladder cancer during that decade, and the team were able to test urine samples from twenty-nine of them, along with samples from 98 other similar participants as controls.

Of the 29 participants who’d developed bladder cancer within the Golestan cohort, the test was able to accurately predict future bladder cancer in 19 (66%) of them, even though urine samples had been taken up to 12 years before clinical diagnosis. Fourteen of these participants were diagnosed with bladder cancer within seven years of urine collection, and the test was able to predict cancer in 12 (86%) of these. The test was accurately negative in 94 of the 98 participants (96%) who would not develop cancer in the future. Among those where the test was negative but who did eventually develop bladder cancer, no cancer was diagnosed until at least six years after the urine collection.

The test was also trialled with colleagues from Massachusetts General Hospital and Ohio State University using samples from 70 bladder cancer patients and 96 controls, taken prior to a cystoscopy. In contrast with the Golestan study, some of these samples were provided by cancer patients on the day they were diagnosed, rather than many years before.

Mutations were found in urine samples from 50 of the 70 patients (71%) whose tumours were visible during the cystoscopy. Some of these were new diagnoses and others involved a cancer recurring. Mutations were not found in 90 of the 96 (94%) patients with a negative cystoscopy.

Dr Le Calvez-Kelm believes these results demonstrate the potential of a genetic urine test for early detection of bladder cancer. She said: “We’ve clearly identified which are the most important acquired genetic mutations that can significantly increase the risk of cancer developing within ten years. Our results were consistent across two very different groups – those with known risk factors undergoing cystoscopy and individuals who were assumed to be healthy.

“Should the results be replicated in larger cohorts, urine tests for these mutations could enable routine screening for high-risk groups, such as smokers or those exposed to known bladder carcinogens through their work.

“This kind of test could also be used when patients come to their doctors with blood in the urine, to help reduce unnecessary cystoscopies. If we can identify bladder cancer early on, before the disease has advanced, then we can save more lives.”

Dr Joost Boormans, a member of the EAU Scientific Congress Office and a urologist at the Erasmus University Medical Center Rotterdam, said: “Research of this nature is very encouraging as it shows that our ability to identify molecular alterations in liquid biopsies such as urine that might indicate cancer is constantly improving.

“While we do need to develop more accurate diagnostics, it’s unlikely that we’ll have a mass screening programme for bladder cancer in the near future. Where a urine test for genetic mutations could show its value is in reducing cystoscopies and scans in bladder cancer patients who are being monitored for recurrence, as well as those referred for blood in their urine. A simple urine test would be far easier for patients to undergo than invasive procedures or scans, as well as being less costly for health services.”

Split-second of evolutionary mutation could have led to mammals, says UCL researcher

A newly-published hypothesis suggests a momentary leap in a single species on a single day millions of years ago might ultimately have led to the arrival of mammals – and therefore humans.

Published in the Journal of Cell Science, Professor John Martin (UCL Division of Medicine) thinks a single genetic mutation in an egg-laying animal may have resulted in the first formation of blood platelets, approximately 220 million years ago.

In mammals and humans, platelets are responsible for blood clotting and wound healing, so play a significant role in our defence response. Unlike our other cells, they don’t have nuclei – so are unique to mammals, since other classes of animal such as reptiles and birds have blood clotting cells with nuclei.

Our platelets formed from megakaryocytes that mature in the bone marrow. When these megakaryocytes are released into the blood stream and reach the very high pressure blood vessels the lungs, they ‘burst’ apart, each cell releasing thousands of platelets inside the bloodstream.

The researchers suggest that millions of years ago a mammalian ancestor – possibly an animal related to the duck-billed platypus – underwent the very first formation of platelets, thanks to a sudden genetic mutation in its blood clotting cells that meant normal cell division did not take place.

If so, those much larger cells might then have been forced to burst inside the first animal’s blood stream, releasing their cytoplasmic fragments. These fragments proved to be more efficient at stopping bleeding, so if this mutation was inheritable, it would have given its offspring a major advantage through natural selection. An animal with this mutation could stem bleeding from fighting or wounds much better than its competitors, and so live longer.

Professor Martin, Professor of Cardiovascular Medicine at UCL, says: “Because of the uniqueness of platelets, it is reasonable to suggest that a unique event led to their origin. This was a radical, internal evolution occurring in a single animal, on a single day, 220 million years ago, and was then reinforced by natural selection.”

Professor Martin and his colleague Professor D’Avino (University of Cambridge) then suggest that this mutation ultimately led to the development, over 120 millions of years, to the placenta, allowing the foetus to be retained inside the mother for longer-term development and thus allowing evolution to achieve live birth. The ability to clot wounds is an essential element of live birth by means of a placenta, since the placenta splits from the female’s uterus during the birth process. The female would not survive birth and therefore not be able to suckle her offspring if she was unable to stem the bleeding.

In their paper, Professors Martin and D’Avino propose experiments that would support their hypothesis, including in vitro and in animal models.

“Without this critical mutation, we suggest mammals would never have evolved, and therefore human beings would not be around today”, says Professor Martin. “With this research, we’ve laid down a marker based on the available evidence – and we’re suggesting these experiments that will either support or refute our hypothesis.”

Signal processing algorithms improved turbulence in free-space optic tests

New signal-processing algorithms have been shown to help mitigate the impact of turbulence in free-space optical experiments, potentially bringing ‘free space’ internet a step closer to reality.

The team of researchers, from Aston and Glasgow universities, used commercially available photonic lanterns, a commercial transponder, and a spatial light modulator to emulate turbulence. By applying a successive interference cancellation digital signal processing algorithm, they achieved record results.

The findings are published in the IEEE Journal of Lightwave Technology.

Free space optical technology wirelessly transmits data as light through the air around us – called ‘free space’ – for use in telecoms or computer networking. Because free space optical communication doesn’t require the expensive laying of fibre cables, it’s seen as an exciting development in bringing communications to places where there is limited existing infrastructure.

But because data is sent as pulses of light, weather conditions can cause problems. A bright sunny day or thick fog can diffract or scintillate the beam of light, creating turbulence which causes data to be lost.

The researchers simultaneously transmitted multiple data signals using different spatially shaped beams of light using a so-called photonic lantern. Turbulence changes the shape of the beams, often losing the signal if only a single simple shape is transmitted and detected, but by detecting light with these shapes using a second lantern, more of the light is collected at the receiver, and the original data can be unscrambled. This can greatly reduce the impact of the atmosphere on the quality of the data received, in a technique known as Multiple-input multiple-output (MIMO) digital signal processing.

Professor Andrew Ellis at Aston University said: “Using a single beam, when a single beam was transmitted, turbulence similar to a hot sunny day destroyed the signal 50% of the time. By transmitting multiple beams of different shapes through the same telescopes and detecting the different shapes, not only did we increase the availability to more than 99%, we increased the capacity to more than 500 Gbit/s, or more than 500 ultra-fast Pure-Fibre broadband links. ”

A project investigating the real-world applications of FSO technology is presently underway in South Africa, where researchers from Aston and Glasgow University are working with the University of the Witwatersrand in Johannesburg to attempt to bring internet access to communities living in informal settlements and schools in underprivileged areas.

The Fibre Before the Fibre Project, aims to provide the internet performance of a Pure-Fibre connection without the need to install cables. It uses a free space optical communication system that can link to remote sites using a wireless optical line of site signal to link to nearby fibre sources in more affluent suburbs.

Professor Ellis said: “Our role in the project is to look at the impact and educational benefit free space optics will have for the school children who will finally be able to access the internet.”