A ‘universal’ cancer vaccine moves closer

via Cardiff University

via Cardiff University

Article Highlights
  • Researchers at Cardiff University have discovered a new type of killer T-cell that offers hope of a “one-size-fits-all” cancer therapy
  • T-cell therapies for cancer - where immune cells are removed, modified and returned to the patient’s blood to seek and destroy cancer cells - are the latest paradigm in cancer treatments
  • The most widely-used therapy, known as CAR-T, is personalised to each patient but targets only a few types of cancers and has not been successful for solid tumours, which make up the vast majority of cancers
  • Cardiff researchers have now discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognises and kills most human cancer types, while ignoring healthy cells
  • This TCR recognises a molecule present on the surface of a wide range of cancer cells as well as in many of the body’s normal cells but, remarkably, is able to distinguish between healthy cells and cancerous ones, killing only the latter
  • The researchers said this meant it offered “exciting opportunities for pan-cancer, pan-population” immunotherapies not previously thought possible
  • T-cells equipped with the new TCR were shown, in the lab, to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells, while ignoring healthy cells
  • To test the therapeutic potential of these cells in vivo, the researchers injected T-cells able to recognise MR1 into mice bearing human cancer and with a human immune system
  • This showed “encouraging” cancer-clearing results which the researchers said was comparable to the now NHS-approved CAR-T therapy in a similar animal model
  • The Cardiff group were further able to show that T-cells of melanoma patients modified to express this new TCR could destroy not only the patient’s own cancer cells, but also other patients’ cancer cells in the laboratory, regardless of the patient’s HLA type
  • Professor Andrew Sewell, lead author on the study and an expert in T-cells from Cardiff University’s School of Medicine, said it was “highly unusual” to find a TCR with such broad cancer specificity and this raised the prospect of “universal” cancer therapy
  • “We hope this new TCR may provide us with a different route to target and destroy a wide range of cancers in all individuals,” he said
  • “Current TCR-based therapies can only be used in a minority of patients with a minority of cancers
  • “Cancer-targeting via MR1-restricted T-cells is an exciting new frontier - it raises the prospect of a ‘one-size-fits-all’ cancer treatment; a single type of T-cell that could be capable of destroying many different types of cancers across the population
  • “There are plenty of hurdles to overcome however if this testing is successful, then I would hope this new treatment could be in use in patients in a few years’ time,” he said
  • “This is truly exciting and potentially a great step forward for the accessibility of cancer immunotherapy.”

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Using genetic engineering to repurpose a strain of beneficial bacteria for use as a safe, sustainable alternative to chemical pesticides

via Harvard University

Researchers at Cardiff University in Wales have used genetic engineering to repurpose a strain of beneficial bacteria for use as a safe, sustainable alternative to chemical pesticides.

The research team found that Burkholderia ambifaria bacteria, when altered with genomic tools, have the potential to act as effective biopesticides, replacing synthetic pesticides that can harm human and environmental health.

“Through our work, we hope to make Burkholderia viable as an effective biopesticide, with the ultimate aim of making agriculture and food production safer, more sustainable and toxin-free,” said lead researcher Eshwar Mahenthiralingam of Cardiff University’s School of Biosciences.

“Beneficial bacteria such as Burkholderia that have co-evolved naturally with plants have a key role to play in a sustainable future,” Mahenthiralingam said. “We have to understand the risks, mitigate against them and seek a balance that works for all.”

This isn’t the first time that biopesticides have been eyed for crop protection.

Though the group of bacteria called Burkholderia successfully protected crops against diseases, in the 1990s they were linked to serious lung infections in people with cystic fibrosis (CF), leading to concerns about their safety. They were eventually taken off the market.

This experience led scientists into other fields of research.  “I have been working with Burkholderia for many years, primarily in relation to CF lung infections, which in turn led to a new line of antibiotic discovery research,” Mahenthiralingam said.

He then teamed up with plant scientist Jim Murray, who heads the School of Biosciences, and doctoral student Alex Mullins to investigate Burkholderia-plant interactions and how they protect plants against disease.

“By sequencing the genomic DNA of the bacteria, we were able to identify Burkholderia‘s antibiotic-making gene, Cepacin,” Mahenthiralingam said in a university press release. “Further testing demonstrated that Cepacin offered highly effective protection against damping off — a horticultural disease caused by a fungus-like organism.”

Using genetic engineering techniques similar to those used to produce live vaccines, the researchers are also exploring how to improve the safety of the bacteria.

Burkholderia split their genomic DNA across three fragments, called replicons,” Mahenthiralingam explained. “We removed the smallest of these three replicons to create a mutant Burkholderia strain which, when tested on germinating peas, still demonstrated excellent biopesticidal properties.”

Further work showed that this Burkholderia mutant did not persist in a mouse lung infection model, opening up the possibility of constructing biopesticidal strains that can still deliver effective plant protection without the risk of causing infection.

Their research is published in Nature Microbiology.

The Cardiff University team, working in collaboration with chemists Greg Challis and Matthew Jenner of the University of Warwick, recently were awarded a £1 million grant from BBSRC to take the research to the next level. The goal is to develop an effective and safe biopesticide that does not build up to harmful levels in the environment.

Learn more: Genetic engineering creates alternative to chemical pesticides

 

 

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The first common genetic risk factors for ADHD

via Mind the Gap Blog

A global team of researchers has found the first common genetic risk factors associated with attention deficit hyperactivity disorder (ADHD), a complex condition affecting around 1 in 20 children. 

Professor Anita Thapar, from Cardiff University, who leads an ADHD research group as part of the Psychiatric Genomics Consortium, said: “This study marks a very important step in beginning to understand the genetic and biological underpinnings of ADHD.

“The genetic risk variants related to this condition play a significant role in brain-related and other core biological processes. The next step is to determine the exact role of these genes in ADHD to help us inform better treatments to support those affected by the condition.”

The team analysed genetic information from over 20,000 people affected with ADHD and over 35,000 people without the condition, the largest genetic study of ADHD to date.

Dr Joanna Martin, a research associate based at Cardiff University’s MRC Centre for Neuropsychiatric Genetics and Genomics, said: “We identified 12 genomic regions at which people with ADHD differed compared to unaffected individuals, and several of these regions are in or near genes with a known relationship to biological processes involved in healthy brain development.”

Further analyses showed that genetic risk for ADHD is shared with risk for other psychiatric and physical disorders, including depression, obesity, type 2 diabetes and lower levels of “good” HDL cholesterol.

The researchers also found that diagnosed ADHD appears to share much of the same genetic background as the traits of ADHD, like inattention and fidgetiness, that can be measured in the general population. Working with the Early Genetics and Lifecourse Epidemiology Consortium (EAGLE), and researchers at Queensland Institute of Medical Research (QIMR), they compared the genetic risk for diagnosed ADHD with genetic markers associated with traits of ADHD in over 20,000 children and found a high correlation between the two, at around 97%.

The correlation between these rather different definitions of ADHD suggests that clinically diagnosed ADHD may be the severe end of a continuous distribution of symptoms in the general population.

Joanna Martin, Research Associate, Division of Psychological Medicine and Clinical Neurosciences

The collaboration consisted of European, North American and Chinese research groups that are part of the Psychiatric Genomics Consortium (PGC), as well as researchers from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) in Denmark.

Professor Anita Thapar said: “This is a landmark study because it involves patients from all over the world. This large number of patient samples has been lacking for ADHD, meaning our understanding of ADHD genetics has lagged behind physical disorders and other psychiatric disorders like schizophrenia and depression. Thanks in large part to Denmark, this is beginning to change.
“Every person with ADHD who has participated in research is making a real difference to advancing our understanding of the condition, and we hope this study leads to higher levels of participation and a greater interest from the UK in supporting ADHD research.”

Although the 12 genomic signals identified in this study are important, they capture only a very small amount of the risk for ADHD. Collectively, common genetic factors accounted for approximately 22% of the risk of ADHD. The role of other sources of genetic risk, for example, rarer genetic changes, as well as environmental factors will also be important to examine in future research studies.

The study ‘Discovery of the First Genome-Wide Significant Risk Loci for ADHD’ is published in Nature Genetics.

 

The Latest on: ADHD

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Could machines learn prejudice by themselves?

via Cardiff University

Showing prejudice towards others does not require a high level of cognitive ability and could easily be exhibited by artificially intelligent machines, new research has suggested.

Computer science and psychology experts from Cardiff University and MIT have shown that groups of autonomous machines could demonstrate prejudice by simply identifying, copying and learning this behaviour from one another.

It may seem that prejudice is a human-specific phenomenon that requires human cognition to form an opinion of, or to stereotype, a certain person or group.

Though some types of computer algorithms have already exhibited prejudice, such as racism and sexism, based on learning from public records and other data generated by humans, this new work demonstrates the possibility of AI evolving prejudicial groups on their own.

The new findings, which have been published in the journal Scientific Reports, are based on computer simulations of how similarly prejudiced individuals, or virtual agents, can form a group and interact with each other.

In a game of give and take, each individual makes a decision as to whether they donate to somebody inside of their own group or in a different group, based on an individual’s reputation as well as their own donating strategy, which includes their levels of prejudice towards outsiders.

As the game unfolds and a supercomputer racks up thousands of simulations, each individual begins to learn new strategies by copying others either within their own group or the entire population.

Co-author of the study Professor Roger Whitaker, from Cardiff University’s Crime and Security Research Institute and the School of Computer Science and Informatics, said: “By running these simulations thousands and thousands of times over, we begin to get an understanding of how prejudice evolves and the conditions that promote or impede it.

The findings involve individuals updating their prejudice levels by preferentially copying those that gain a higher short term payoff, meaning that these decisions do not necessarily require advanced cognitive abilities.

“It is feasible that autonomous machines with the ability to identify with discrimination and copy others could in future be susceptible to prejudicial phenomena that we see in the human population,” Professor Whitaker continued.

“Many of the AI developments that we are seeing involve autonomy and self-control, meaning that the behaviour of devices is also influenced by others around them. Vehicles and the Internet of Things are two recent examples. Our study gives a theoretical insight where simulated agents periodically call upon others for some kind of resource.”

A further interesting finding from the study was that under particular conditions, which include more distinct subpopulations being present within a population, it was more difficult for prejudice to take hold.

“With a greater number of subpopulations, alliances of non-prejudicial groups can cooperate without being exploited. This also diminishes their status as a minority, reducing the susceptibility to prejudice taking hold. However, this also requires circumstances where agents have a higher disposition towards interacting outside of their group,” Professor Whitaker concluded.

 

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A potential new drug to treat two life-threatening tropical diseases: schistosomiasis and fascioliasis

via Debug Lies

Derived from nature, a potential new drug to treat two life-threatening tropical diseases has been discovered as a result of collaboration between two Welsh universities.

The team of researchers, led by Professor Andrew Westwell from Cardiff University, has successfully created a drug compound, from the goji berry plant, that is active against the parasites that cause schistosomiasis and fascioliasis.

Although not widely known, schistosomiasis is the most devastating human parasitic disease after malaria, with approximately 600 million people currently affected, and causing approximately 300,000 deaths per year. Likewise, 17 million people are currently infected with fascioliasis, with figures set to increase.

Schistosomiasis is caused by a waterborne parasite, while fascioliasis is caused by a foodborne parasite.  Both of these neglected diseases are treated with a single drug, which is widely administered to the population where these diseases are most prevalent.  However, this type of single treatment often leads to drug resistance, which is now the case for many people at risk of contracting these diseases.

As a result, a team of researchers at Cardiff University joined forces with Aberystwyth University’s Institute of Biological, Environmental and Rural Sciences, led by Professor Karl Hoffmann, in a collaboration to find a new drug treatment.

Speaking of the research, Professor Westwell from Cardiff University’s School of Pharmacy and Pharmaceutical Sciences, said: “Discovering a potential new treatment for two such prevalent diseases is an exciting find and we hope that this research will lead to major health benefits for some of the world’s poorest people who are at risk of contracting Schistosomiasis and Fascioliasis.”

Learn more: Potential new drug for two life-threatening diseases

 

 

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