UCD researchers are making their mark in the exciting field of precision medicine

Personalised Healthcare

IT HAS BEEN 16 YEARS since the Human Genome Project concluded – an unprecedented international research effort to identify and map all the genes that make up our DNA. The work heralded a new era, the birth of a new science known today as Precision Medicine, and it is changing the fundamental paradigm at the heart of disease diagnostics and treatment.

BREAKING GROUND

Professor Des Higgins

UCD researchers have been at the centre of this new science throughout its development. Once the genome was sequenced, scientists needed a way to effectively manage all the data sequencing produced. Enter Professor Des Higgins of UCD School of Medicine and the UCD Conway Institute, one of the world’s leading experts in bioinformatics, who developed a groundbreaking programme for aligning the sequences and making sense of the data. This software was the subject of his 1994 paper in the international scientific journal Nature – just four years after the Human Genome Project began. This paper went on to become, to this day, one of the top ten most cited research publications of all time, and is also cited in patents for over 27,000 products produced by organisations including Pfizer, Bristol- Myers Squibb Company, and the United States’ government.

Professor Walter Kolch

Leading Precision Medicine at UCD today is Professor Walter Kolch, who joined the University ten years ago along with Professor Boris Kholodenko to establish Systems Biology Ireland (SBI). Kolch, an Austrian medic turned biochemist, and Kholodenko, a Russian physicist, combined their skills to build dynamic models of the human system. Attracting researchers from all over the world, SBI soon became a recognised leader in the Precision Medicine field. It was one of the first groups to model not only the impact of your DNA but also the impact of your environment, lifestyle and nutrition on how you treat disease.

As SBI reaches its ten-year anniversary at UCD, they can look back with pride at what they, and UCD, have achieved. Kolch is now number two* in the world in the area of precision oncology (precision medicine applied to cancer), while Kholodenko is number one* in the world in computational and mathematical modelling. Having proven their work in the lab, they want to make an impact on the lives of Irish patients.

Explaining it all, Professor Kolch said: “We are all different and we all react differently. The flu will affect each of us differently and so too will the treatment. It was 2,500 years ago when Hippocrates said, ‘It is far more important to know what person the disease has than what disease the person has’. In the genomics age of technology we now have the means to treat the person, not the disease.”

*In total citation Google Scholar

THE COST OF IMPRECISION

At its core, Precision Medicine uses data about a person’s genes (genomics), as well as environmental factors such as lifestyle and nutrition (the other ‘omics’ such as metabolomics and proteomics), to understand the unique pathways of a disease or drugs in that person. With this information doctors can then prescribe the right treatment in a timely fashion, saving the wasted resources and time our current “trial and error” methodology incurs, while greatly improving response rates.

“For the top ten best-selling drugs in medicine today, the response rate is only between four and 24 per cent of patients. That’s not because the drugs are badly designed, it’s because we are all different and they affect us differently. A lot of patients don’t have the luxury of time for a trial and error approach, and it is very expensive,” Professor Kolch explained.

But with a diagnosis founded on integrated ‘omic’ data from a patient, the results are substantially better – in one example increasing survival rates for lung cancers from ten to 60 per cent.

UCD Professor of Paediatric and Adolescent Medicine and Consultant Paediatric Haematologist at Our Lady’s Children’s Hospital, Crumlin, Professor Owen Smith pointed to the benefits of Precision Medicine over conventional medicine in treating childhood cancers  – a specialist area that sees higher cure rates than in adult cancers but sees greater rates of secondary cancer and other problems continuing into adulthood.

“To paraphrase Bill Clinton, it’s the mutation, stupid. We need to know how to kill what’s causing the cancer and not harm the rest of the body along with it. Targeting the pathways with Precision Medicine would enable doctors and drugs manufacturers to treat childhood cancers more effectively without the ‘friendly fire’ of toxicity caused by cancer drugs.” In addition to causing secondary cancers in children, this toxicity in their bodies can lead to deafness, infections and chronic health issues, causing economic and social problems long into the future.

Looking at a different area of health, Conway Fellow and head of the metabolomics research group at the UCD Institute of Food and Health, Professor Lorraine Brennan cites another of the overwhelming challenges facing us today – obesity – and how a precision approach could better serve people. “At the moment, first line obesity management is weight loss through a combination of dietary and physical activity behaviour changes. Unfortunately, this ‘one size fits all’ approach  doesn’t  work  for most people.”

The inter-relationships between environmental, biological and social determinants of obesity are complex. Patients can be described as metabolically healthy obese or metabolically unhealthy obese, with the latter having obesity-related metabolic complications and both groups exhibiting different responses to different therapeutic approaches. According to Professor Brennan: “A more personalised approach that considers obese individuals according to their type may be more advantageous for the individual and have implications in terms of developing more tailored obesity treatments.”

Furthermore, having access to ‘omics’ data on individuals would help clinicians expand on research into personalised nutrition based on genetic make-up, with many potential benefits for a person’s health and wellness beyond treating diseases.

PARTNERSHIP IS KEY

In March this year, UCD announced a partnership with Genomics Medicine Ireland (GMI), a recently formed company that will create 600 new jobs taking advantage of this emerging field of science. The genomics research collaboration between UCD and GMI will look at diseases such as multiple sclerosis, diabetes, inflammatory bowel disease and Alzheimer’s and seek to understand the genetic basis of these diseases.

The research can be used by pharma companies to produce medicines that deliver better, more targeted treatment, and in time will also be used by doctors and clinicians to improve diagnostics and streamline screening for genetic diseases. Public-private partnerships such as this will be part of the solution to bring the benefits of this breakthrough science to Irish patients.

SO, WHAT’S NEXT?

Opportunities and challenges remain for Kolch, Kholodenko and the team, to bring Precision Medicine to its full potential. “The bottleneck today is generating the computational models we need to interpret the data. Then we can make a full digital simulation of a person – your ‘digital twin’ – and doctors can analyse and optimise and then provide the best therapeutic plan first time around.” This is what UCD’s Systems Biology Ireland will be concerned with from now on – to gain for the first time a fully holistic view of the patient, to achieve better health for all in the future.

Having an Impact

UCD Research

Dr Crystal Fulton from the School of Information and Communication Studies was the winner of UCD’s 2018 Research Impact Competition. Her research, “Playing Social Roulette: The impact of gambling on individuals and society in Ireland”, drove a conversation about a problem that negatively impacts between 224,000 and 440,000 people. Significantly, the Department of Justice and Equality funded a follow-up investigation, both as a driver for legislative change and content for new regulations.

Dr Fulton’s national study began with a two-year exploration of the social impact of harmful gambling, involving in-depth interviews with critical stakeholders: addiction counsellors; recovering gamblers and gamblers’ social connections; as well as a focus group with gambling industry representatives.

The follow-up study in 2016 examined international trends in the literature about gambling and consulted with stakeholders about potential changes to legislation.

New Fellows

UCD gained two new Marie Sklodowska Curie International Fellows at the Performance Engineering Laboratory. Co-director of PEL, Professor John Murphy from the School of Computer Science welcomed Dr Long Chen from Eindhoven Technical University in Germany and Dr Madhusanka Liyanage from the University of Oulu in Finland. MSCA Fellowships are extremely competitive and prestigious awards granted under the Excellent Science pillar of Horizon 2020, and UCD anticipates some exciting developments from their respective projects in data networks for large-scale data analytics and 5G mobile network security.

RIA Gold Medallist

Kathleen James-Chakraborty

Professor Kathleen James- Chakraborty from UCD School of Art History and Cultural Policy received the Royal Irish Academy’s Gold Medal in 2019 for her work in Humanities – the first woman ever to receive the award.

Yale graduate and architectural historian, Professor James-Chakraborty currently serves on the boards of the Buildings of Ireland Charitable Trust, the Chester Beatty Library, the National Museum of Ireland and the Society of Architectural Historians.

Biopharma Booster

David Brayden Group

BEACON Bioeconomy SFI Research Centre, led by UCD, announced a public-private partnership in 2019 with genomics-focused AI platform creator Nuritas, to investigate oral bioavailability in naturally occurring peptides from food and food by-products.

Led by Professor David Brayden from UCD School of Veterinary Medicine, and CSO and Founder of Nuritas, Dr Nora Khaldi, the partnership is a potential game-changer for the biopharma industry. The €22.2m BEACON centre was launched last October as part of a national bioeconomy strategy

 

Eoin Carolan

UCD College of Social Sciences and Law continued to show its mettle, with over €10m in new external research awards in 2017-18. Most recently, Professor Eoin Carolan from the  UCD Sutherland School of Law was awarded a prestigious ERC grant of €2m to investigate how the separation of powers in different constitutional systems is affected by current social and political trends. Sutherland School of Law is ranked in the top 50 of THE world ranked law schools.

In the School of Education, Professor Dympna Devine was awarded over €2.1m from the National Council for Curriculum and Assessment, for the most wide-ranging study into the primary school system ever funded by the State.

Food for Thought

Food science continues to be a strong growth area at UCD. Our multidisciplinary technology centre Food for Health Ireland gained over €14.4m in funding from Enterprise Ireland and industry for a third phase, covering a further five years from 2019 to 2023.

Led by Professor Dolores O’Riordan, FHI 3 commenced in January, backed by industry partners Glanbia Ingredients Ireland, Kerry Group, Carbery and Dairygold. The centre is now primarily focused on commercialising its research outputs, principally value-adding innovations for food, especially dairy ingredients.