Trinity Scientists discover shared genetic origin for MND and schizophrenia

Researchers from Trinity College Dublin have shown for the first time that Motor Neurone Disease (MND) — also known as Amyotrophic Lateral Sclerosis (ALS) — and schizophrenia have a shared genetic origin, indicating that the causes of these diverse conditions are biologically linked. The work has just been published in the prestigious journal Nature Communications.

By analysing the genetic profiles of almost 13,000 MND cases and over 30,000 schizophrenia cases, the researchers have confirmed that many of the genes that are associated with these two very different conditions are the same.

In fact, the research has shown an overlap of 14% in genetic susceptibility to the adult onset neuro-degeneration condition ALS/MND and the developmental neuropsychiatric disorder schizophrenia.

While overlaps between schizophrenia and other neuropsychiatric conditions including bipolar affective disorder and autism have been shown in the past, this is the first time that an overlap in genetic susceptibility between MND and psychiatric conditions has been shown.

Dr Russell McLaughlin, Ussher Assistant Professor in Genome Analysis at Trinity College Dublin, and lead author of the paper said: “This study demonstrates the power of genetics in understanding the causes of diseases.”

“While neurological and psychiatric conditions may have very different characteristics and clinical presentations, our work has shown that the biological pathways that lead to these diverse conditions have much in common.”

Professor of Neurology in Trinity and Consultant Neurologist at the National Neuroscience Centre at Beaumont Hospital Dublin, Orla Hardiman, is the senior author and lead investigator on the project.

Professor Hardiman said: “Our work over the years has shown us that MND is a much more complex disease than we originally thought. Our recent observations of links with psychiatric conditions in some families have made us think differently about how we should study MND. When combined with our clinical work and our studies using MRI and EEG, it becomes clear that MND is not just a disorder of individual nerve cells, but a disorder of the way these nerve cells talk to one another as part of a larger network.”

She continued: “So instead of thinking of MND as a degeneration of one cell at a time, and looking for a ‘magic bullet’ treatment that works, we should think about MND in the same way that we think about schizophrenia, which is a problem of disruptions in connectivity between different regions of the brain, and we should look for drugs that help to stabilise the failing brain networks.”

“The other significant issue that this research brings up is that the divide between psychiatry and neurology is a false one. We need to recognise that brain disease has many different manifestations, and the best way to develop new treatments is to understand the biology of what is happening. This will have major implications for how we classify diseases going forward, and in turn how we train our future doctors in both psychiatry and neurology. That in itself will have knock-on consequences for how society understands, approaches and treats people with psychiatric and neurological conditions.”

The new research was prompted by earlier epidemiological studies by researchers at Trinity, led by Professor Hardiman. These studies showed that people with MND were more likely than expected to have other family members with schizophrenia, and to have had another family member who had committed suicide.

This was first noted as family histories were ascertained from people with MND in the National ALS Clinic and was subsequently investigated as part of case control studies in Ireland in which over 192 families with MND and 200 controls participated. Details of over 12,000 relatives were analysed and the rates of various neurological and psychiatric conditions calculated in family member of those with MND and controls. This work was subsequently published in the prestigious American journal the Annals of Neurology in 2013.

This led the Trinity group to team up with European collaborators in MND including the University of Utrecht, Kings College London and members of the Project MinE and Psychiatric Genome Consortia to see if these epidemiological observations could be due to a genetic overlap between MND and schizophrenia.

The Trinity group, along with their partners in the University of Utrecht, will continue to study the links between MND and psychiatric conditions using modern genetics, epidemiology and neuroimaging, and in this way will develop new and more effective treatments that are based on stabilizing disrupted brain networks.

The full paper is available here:

TCD – New discovery to prevent infections spreading on medical devices

Microbiologists from Trinity College Dublin have discovered how to prevent bacteria from growing on medical devices such as hip replacements and heart valves that are implanted in the human body.

Their discovery is a step towards developing new preventative strategies that could have a direct impact on the recovery of patients in the immediate aftermath of a surgical operation.

Medical devices are routinely used in modern medicine to prevent and treat illness and disease but their use is compromised when an accumulation of bacteria called “biofilms” attach to the device surface after it is implanted in the human body.

Communities of these bacteria called ‘staphylococci’ grow on catheters, heart valves and artificial joints, and avoid being killed by antibiotics and the human immune system, which means healthcare professionals often have to remove and replace the medical devices. Each incident of biofilm infection costs the healthcare system €50,000 – €90,000.

The research team — led by Dr Joan Geoghegan, Assistant Professor of Microbiology in Trinity’s School of Genetics and Microbiology — is studying new ways to prevent medical device-related infection.

Dr Joan Geoghegan and Leanne Hays' work may pave the way to new options for surgeons that reduce the risk of bacterial infection for patients.
Dr Joan Geoghegan and Leanne Hays’ work may pave the way to new options for surgeons that reduce the risk of bacterial infection for patients.

Their recent breakthrough published in the prestigious journal Proceedings of the National Academy of Sciences of the USA shows that it is possible to prevent communities of staphylococci from forming by targeting the linkages that hold the bacteria together.

In collaboration with atomic force microscopy expert Professor Yves Dufrêne and his team at the Université Catholique de Louvain, Leanne Hays, PhD student in Trinity’s Department of Microbiology, has found that it is possible to stop bacteria from attaching to surfaces and to each other by using a small blocking molecule.

The target of the blocking molecule was a protein attached to the surface of the bacteria called ‘SdrC’. In laboratory experiments the blocking molecule prevented the SdrC protein from recognising other bacteria, which stopped the staphylococci from growing as biofilm communities.

Dr Geoghegan said: “These new findings show that it is possible to stop bacteria from building communities using molecules that specifically target proteins attached to the surface of the bacteria. This exciting breakthrough will inform the design of new, targeted approaches to prevent biofilm formation by staphylococci and reduce the incidence of medical device-related infection.

The research at Trinity College Dublin was supported by an Irish Research Council Government of Ireland Postgraduate Scholarship awarded to Leanne Hays.

TCD geneticists in breakthrough on autism and epilepsy

Move could open up new treatment options for difficult to treat conditions

Professor in genetics and head of department Aoife McLysaght led the research which focused on neurodevelopmental disorders including ADHD, developmental delay, schizophrenia and intellectual disability.

It involved a novel new way to look at disease-related DNA not by studying the genes as they are today but by watching their evolution over time, said Prof McLysaght, whose research is funded by the European Research Council.

The researchers were interested in places where the DNA made multiple copies or deletions of itself. They also wanted to see what genes near these places were doing.

Humans all have these duplicates and deletions that vary in size and seem random, but the Trinity team noticed a pattern when they were near a gene associated with a disease condition.


The copies and deletions tended to be longer near these genes but there were fewer of them, something that encouraged Prof McLysaght to make a link with “Goldilocks”.

“Our idea was that there must be some genes within these regions with Goldilocks properties – too much or too little duplication and things don’t work properly,” she said. “The number of copies must be just right.”

The group looked back over our evolutionary history, searching for genes that did not seem to tolerate too much or too little variation.

It found that there was far less variation around genes associated with neurodevelopmental disorders compared to genes that had no association with disorders.

This held true for humans but was also true for other mammal species including sheep, dogs, rabbits and gorillas.

Details of the work were published on Wednesday in Nature Communications.

The research shows that our evolutionary history could be useful for understanding human disease, Prof McLysaght said.

It could also make it easier to identify genes linked with a developmental condition.

“These metrics also allow us to home in on a short list of genes as candidates for the diseases in question,” she said.

Isolating disease-related genes will help explain why these conditions arise, provide better diagnostic tools and potentially help to develop new therapies, she said.

Students from Trinity recognized by ‘Junior Nobel Prize’

The Undergraduate Awards (UA) gathered 150 of the world’s top undergraduate students in Dublin for the 2016 UA Global Summit in Dublin, including seven students from Trinity College Dublin.

Cited as the ultimate champion of high-potential undergraduates, and often referred to as a “junior Nobel Prize”, The Undergraduate Awards is the world’s largest international academic awards programme, recognising excellent research and original work across the sciences, humanities, business and creative arts.

The Undergraduate Awards received a record number of submissions in the 2016 programme, totaling a massive 5,514 papers from undergraduates in 244 institutions and 121 nationalities. In each category, the Global Winner is the highest-performing paper overall and also within each category the Regional Winner is the highest performing Highly Commended paper from their region. Highly Commended Entrants are those who were ranked in the top 10% of submissions in each category.

In total, 58 different universities and 37 different nationalities were represented at the UA Global Summit this year. Ryerson University, Canada; Stanford University, USA; University of Johannesburg, South Africa and the University of Helsinki, Finland were among the institutions represented at the event.

The students received their medals and certificates at the UA Global Summit and were addressed by keynote speaker Dr. Mae Jemison, NASA Astronaut.

The winning students from Trinity College Dublin are:

  • Eoin O’Leary – Global Winner – Social Sciences: Anthropology & Cultural Studies
  • Stephen Cox – Global Winner – Literature: Non-English
  • Naoise Dolan – Global Winner – Literature: English
  • Ben Price – Regional Winner Island of Ireland – Art History, Music, Film & Theatre
  • Rory Patrick Joseph Hennessy – Regional Winner Island of Ireland – Law
  • Conor Mc Glynn – Regional Winner Island of Ireland – Philosophy
  • Francis Ian Aristosa – Highly Commended – Nursing & Midwifery

Speaking about this year’s Winners and Highly Commended Entrants, CEO of The Undergraduate Awards Louise Hodgson said “This is a huge achievement for Trinity College Dublin and its students. UA received the highest number of submissions to date with only the best papers making it through the judging process –  the competition was extremely tough and the Judges were astounded at the high quality of undergraduate research in the programme this year. Congratulations to this year’s successful entrants”.


The UA Global Summit took place the week of November 8th-11th in Dublin across several beautiful venues including Farmleigh House, St. Patrick’s Cathedral and City Hall, Dublin.


About The Undergraduate Awards

The Undergraduate Awards is the world’s largest international academic awards programme, recognising innovation and excellence at undergraduate level. Cited as the ultimate champion for high-potential undergraduates, UA identifies leading creative thinkers through their undergraduate coursework and provides top performing students with the support, network and opportunities they require to raise their profiles and further their career paths.

Trinity researchers win Royal Society University Research Fellowships

Researchers from Trinity College Dublin have won three of the five prestigious Royal Society University Research Fellowships awarded in Ireland this year.

The University Research Fellowship programme, which is co-funded by Science Foundation Ireland, aims to provide outstanding early career scientists, who have the potential to become leaders in their chosen fields, with the opportunity to build an independent research career.

The newly appointed university research fellows at Trinity are Dr. John Goold (School of Physics), Dr. Richard Hobbs, and Dr. Aidan McDonald (both School of Chemistry).

Dr. Goold will be working on ‘thermodynamics for quantum technologies’.

Dr Goold said: “Thermodynamics is a theory with a remarkable range of applicability, successfully describing the properties of macroscopic systems ranging from refrigerators to black holes. With both the industrial and electronic revolutions behind us, we are currently pushing technology towards and beyond the microscopic scale to the border of where quantum mechanical effects prevail. Currently, there is a large multidisciplinary interest surrounding the thermodynamic description of non-equilibrium finite quantum systems from both a fundamental and applicative view point.”

“With this Royal Society-SFI University Fellowship I will undertake a program of research which aims at addressing several key problems which are at the heart of this rapidly developing field known as quantum thermodynamics.”

Dr. Hobbs received the award for his work on ‘Engineering energy transfer on the nanoscale at plasmonic surfaces’. Metal nanostructures provide a means to funnel energy carried by light into nanoscale volumes in materials where that energy may be used to drive electronic, thermal and chemical processes.

Their ability to manipulate light on the nanoscale and enhance light-matter interactions means that they are a material of considerable promise for applications in photochemistry and optoelectronics.

Dr Hobbs said: “The Royal Society-SFI University Research Fellowship will support my research at Trinity for the next five years. By hosting the fellowship at Trinity, I will have access to the fantastic state-of-the-art nanofabrication and electron microscopy facilities available through CRANN and AMBER. I am looking forward to collaborating with researchers at these centres and within the School of Chemistry to tackle big problems with nanomaterials.”

Dr McDonald’s research focuses on the chemistry of synthetic compounds that allow us to understand metal-containing enzymes that play a pivotal role in human health.

Dr McDonald said: The award of a Royal Society-SFI University Research Fellowship is a great honour for me, and is a result of the tremendous support that I have received from the School of Chemistry and AMBER research centre. The fellowship will support my research group’s work in fundamental Inorganic Chemistry towards designing powerful oxidation catalysts and elucidating metalloenzyme function.

Research Projects Officer at Trinity, Tony Flaherty, said: “This funding scheme has only recently been opened up to Irish applicants and the Research Development Office has put significant resources into supporting Trinity applications, including running dedicated workshops on grant writing with external experts.”

“We are delighted to see this level of success at such an early stage. We hope to build on this success in the coming years, and look forward to great things from our three new Royal Society Fellows.”

Trinity divests from fossil fuels as part of global campaign

Trinity answers the call of Student Campaign ‘Fossil Free TCD’ and becomes first university in Ireland to pull investment in fossil fuels

Trinity College Dublin has decided to sell off all of its investments in companies whose primary business is in the extraction of fossil fuels. It is the first university on the island of Ireland to divest its oil, coal and gas investments. Trinity ‘s decision to divest was  in response to an impressive 15 month student campaign  ‘Fossil Free TCD’  and was made last November. They are joining a global announcement today in London [December 12th, 2016] along with 677 institutions and 58,399 individuals worldwide who have pledged to divest fossil fuels as part of the global ‘Divest-Invest’ campaign.  They include governments and investors from 77 countries including banks, pension funds, insurance companies and institutes in the health, education, philanthropy and faith sectors.  Together they represent $5 trillion in assets.

The World Health Organisation estimates that climate change is already claiming 150,000 lives per year.  One year ago today at the Paris COP21, world leaders agreed  that global warming must be limited to below 2 degrees if we are to prevent catastrophic climate change.  However, a recent study by Oil Change International found that we will already exceed 2 degrees of warming if all the carbon in the industry’s current operating fields and mines is burned.

Trinity students have joined students from all over the world in calling on universities and other institutions to stop funding the cause of climate change. Trinity has responded to their call.

 L-R: Colm Tong, Áine O'Gorman, Dr Patrick Prendergast, Deirdre Duff, Julie Fitzsimmons
L-R: Colm Tong, Áine O’Gorman, Dr Patrick Prendergast, Deirdre Duff, Julie Fitzsimmons

The Provost of Trinity College Dublin, Dr Patrick Prendergast said: “This is a proud day for Trinity College Dublin, the first university in Ireland to sign up to fossil free divestment. Our decision puts the University at the forefront of sustainability and institutional fossil fuel divestment nationally.  Trinity intends to play our part in delivering the Paris Agreement. We aspire to be a leader in sustainability and climate solutions in every aspect of the College, not only in investments but in our research, and also in how the campus operates.   We made this decision following the impressive campaign of our own students ‘Fossil Free TCD’. We responded to their call and today is an historic day for all of us as we participate in this global announcement along with universities and multiple organisations from around the world.”

Trinity Students’ Union President, Kieran McNulty added: “We in the Students’ Union are delighted at the College’s decision to divest from fossil fuels. This was a student-led campaign I hope this spurs on other universities and companies in Ireland to divest. Never doubt the power of young people and students to make change.”

Fossil Free TCD spokesperson, Deirdre Duff, concluded:  “By joining the international divestment movement Trinity is sending a message that the fossil fuel era is ending. The transition to renewable energy must be accelerated rapidly if we are to safeguard the future of human civilisation. If the fossil fuel industry follows its business plan, vast areas of our planet will become uninhabitable. The share price of fossil fuel companies assumes that their proven fossil fuel reserves will be consumed. However the industry has around five times more carbon in these reserves than can be burned if warming is to be limited to 2 degrees as agreed by the world’s governments.   Therefore leading financial experts have highlighted the risks of fossil fuel resources becoming ‘stranded assets’, representing a dangerous ‘carbon bubble’.  So a decision to divest makes good financial sense.”

Trinity now plans to sell up to €6 million of investments in oil companies.  Trinity’s endowment fund dates back to more than 200 years. It is supported by legacies from donors. Capital is used to generate an annual return which is used to finance the academic and student support needs of the University.

About Divest-Invest

Divest-Invest is a global coalition that responds to climate change by encouraging people, groups and institutions to divest from fossil fuels and invest in climate solutions: for more information.

US Department of Health funds five research projects at TCD

The US Department of Health & Human Services (DHHS) has awarded Trinity researchers significant funding to pursue five ground-breaking research projects in a number of fields related to human health, including neuroscience, psychiatric illness and pulmonary disease.

Professor of Psychiatry, Michael Gill, and Professor in Psychiatry, Aiden Corvin, were successful as partners funded by the NIH National Institute of Mental Health (and co-funded by Science Foundation Ireland) for a project led by the University of North Carolina.

The Trinity team will lead a global research effort, applying genome sequencing to identify genes that predispose to major mental disorders in multiply affected families.

Professor Corvin said: “It will be an honour to lead this ambitious programme working with researchers and families from around the world as part of the international Psychiatric Genomics Consortium initiative.”

Professor of Pharmaceutics and Pharmaceutical Technology, Anne-Marie Healy, was successful as a partner within 2 NIH grants led by Professor John Fahy of the University of California. She will focus her research on carbohydrate-based therapies for people living with lung disease.

Assistant Professor in Neuroscience, Colm Cunningham, was funded by the National Institute on Aging of the National Institutes of Health (NIH). His five-year programme is focused on how the loss of a chemical called acetylcholine from the brain leaves it vulnerable to inflammation arising during acute illness.

Professor of Neurology Orla Hardiman’s pre-eminence in the study of Motor Neuron Disease (MND) was recognised by the US Center for Disease Control (CDC), and she will now coordinate a project that includes partners from Latin America and Italy. The project will examine the relationship between MND prevalence in differing and mixed-race populations. Professor Hardiman will establish new registers of the incidence, prevalence and risk factors for MND in three Latin American countries, Cuba, Chile and Uruguay. This is the first time that the US government has provided federal funding for research in Cuba.

Trinity’s Research Development Office supported these projects as part of the Colleges Funding Diversification Strategy. This strategy aims to optimise the funding for research in Trinity by exploiting opportunities beyond the traditional national and EU funding programmes.

Research Project Officer at TR&I, Tony Flaherty, said: “This investment of US Government funding is a huge endorsement in the world-leading health research that is ongoing in Trinity, and in the societal impact it is having globally.”

International employers view Trinity graduates among the elite

Graduates from Trinity College Dublin are among the most employable in the world, according to the 2016 Global Employability University Rankings. Trinity is the only Irish university to appear in the rankings, where it sits at number 134.

This unique ranking was provided by 1) surveying a panel made up of recruiters from 20 countries, who were at a management level and had experience of hiring graduates, and 2) by surveying 3,450 managing directors of international companies.

The survey effectively asked what recruiters look for in university graduates, before ranking universities based on the number of votes they received from international respondents.

Importantly, Irish recruiters were not included in the first panel. As a result, Trinity’s presence in the Top 150 shows just how highly its graduates are valued by international employers, because it secured its votes solely from the managing directors of large, internationally recruiting companies.

These companies were free to cast up to 10 votes for universities whose graduates they valued highly, and they were also allowed to vote for those coming from local (national) universities as well as those from other countries.

The rankings were designed and commissioned by the French Human Resources consulting agency, Emerging. They are a valuable tool for employers, but also for students in choosing their university.

Commenting on the results, Director of the Careers Advisory Service at Trinity, Sean Gannon, said: “Employability is not simply the ability to get a job directly after graduation but is a measure of present and future career success. That success draws on a wide range of knowledge, skills and attributes which are developed not only in the formal curriculum but through the wider student experience.”

“In light of the likely challenges facing the Irish economy in the years ahead this ranking underlines the importance of the current work on curriculum reform in the College with the emphasis on the development of 21st century skills and key graduate attributes.”

New genes from scratch – Trinity geneticist discusses the evolution of DNA

Professor in Genetics at Trinity, Aoife McLysaght, explained how new genes evolve and how they sometimes become essential as she addressed a packed audience while delivering the 2016 JBS Haldane Lecture at the Royal Institution of Great Britain in London.

The DNA in every living cell, including all of those in our bodies, has been passed down from our ancestors, going right back to the origins of life.

In recent years, geneticists have used new technologies to compare the all-important DNA sequences in different species and individuals that explain why life’s myriad variations exist. Having direct access to the blueprints that have sprung from billions of years of evolution has provided these geneticists with incredible information about how – and why – evolutionary novelties arise.

Professor McLysaght, who was the first to discover a set of new genes that only occur in humans, explored these ideas in her lecture. She placed a particular emphasis on our rapidly growing understanding of how new genes evolve, and on the the link between new genes and disease, including cancer.

New genes may appear in genomes in a variety of ways, but much of Professor McLysaght’s work focuses on the origins of de novo genes, which are those that arise from sections of the DNA code which previously did not code for proteins.

Professor McLysaght said: “It is a huge honour to have been awarded the JBS Haldane Lecture Prize. It is a real challenge to present complex scientific ideas to a lay audience in a way that is comprehensible while at the same time not losing the excitement of the work, and I was thrilled to deliver this lecture to a tremendous audience.”

“It was a fantastic opportunity to explain my recent work on the evolution of new genes, as well as the broader context, to the audience at the Royal Institution. I was also able to speculate on how the special evolutionary conflicts around the origin of new genes might explain why so many new genes have a role in cancer.”

The lecture is named in honour of John Burdon Sanderson (JBS) Haldane, who was a British scientist known for his contributions to the fields of physiology, mathematics, evolution and genetics. He is credited with laying the foundations for modern evolutionary synthesis, having created models of population genetics, which essentially unified the theories of Mendelian genetics and Darwinian evolution via natural selection in the early 20th Century.

The lecture is organised by the Genetics Society UK. Taking place once each year, it recognises an individual for his/her outstanding ability to communicate topical subjects in genetics research.

TCD Immunologists Unearth Key Piece of MRSA Vaccine Puzzle

Immunologists from Trinity College Dublin have unearthed a key piece of the MRSA vaccine puzzle by identifying specific ‘helper’ cells whose role in the immune response is critical in affecting infection outcomes.

The immunologists were able to develop a model vaccine, which targeted these ‘T-helper type 1’ cells, and then showed experimentally that its use led to improved infection outcomes.

Assistant Professor in Immunology in the School of Biochemistry and Immunology at Trinity, Dr Rachel McLoughlin, said: “To design an effective vaccine it is imperative you know how a bacterium interacts with its host. By screening patients with Staphylococcus aureus blood stream infections we were able to isolate key players in the immune system that dealt with these infections and then designed a model vaccine that effectively sparked them into action.”

The World Health Organisation (WHO) warns of an impending “post-antibiotic era,” with the potential to undermine modern medicine. Anti-microbial resistance is a global crisis that demands the development of new antimicrobials, but developing alternatives to antibiotics such as vaccines would prevent infection in the first place.

The bacterium S. aureus is a major cause of healthcare-associated infections, and blood stream infections caused by S. aureus are associated with significant mortality. Resistance in S. aureus to the main antibiotic used for treatment, methicillin, was first reported in the 1960s and, over the past decades, antibiotic resistant S. aureus, or MRSA, has become endemic in hospitals throughout the world.

The incidence of MRSA blood stream infections in Irish hospitals has been steadily decreasing in recent years, but is still higher than several other European countries, which means there is an urgent need to develop a vaccine to prevent this infection.

To date, around eight promising candidate vaccines have failed in clinical trials, despite showing promise in pre-clinical models. Traditional approaches to vaccine development have thus failed to develop an effective weapon against MRSA.

We now know that cellular immunity (involving ‘T-cells’) is vitally important in protection against S. aureus infection, because individual T-cell subsets are very important for activating phagocytes – the immune cells that ingest and kill bacteria.

Dr McLoughlin and her colleagues found that ‘T-helper type 1 cells’ were elevated in patients following S.aureus infection. Their model vaccine, which jolted these cells into action, improved infection outcomes. The results therefore support the design of vaccines that specifically target these cells in humans.

Dr McLoughlin said: “This study demonstrates the importance of truly translational research. Using pre-clinical models we identified an immune mechanism important for protection against S. aureus infection, but it was via collaboration with clinicians at three Dublin teaching hospitals that we were able to translate these findings to show the same mechanism of immunity is relevant in human infection. Our findings will directly inform the design of next-gen anti S. aureus vaccines and could significantly increase our chances of realizing an effective vaccine to protect patients from MRSA.”

The research was supported by funding from the Health Research Board (HRB) and the Wellcome Trust. A copy of the journal article, just published in PLOS Pathogens, is available on request. The article can be viewed here.