Dundee team leading groundbreaking cancer and Parkinson’s research given five-year funding boost to continue life-saving work

• Vital work by Dundee-based cell biology researchers, who have already developed a drug to treat skin cancer, to continue thanks to further Government backing.
• Almost £30 million could potentially unlock new treatments for Motor Neurone Disease, Crohn’s and more by supporting research into how signals are transmitted within the body’s cells.
• Science and Technology Secretary will announce funding at the Universities UK conference as he sets out his vision for harnessing the power of higher education.

Dundee-based researchers with a track record of devising treatments for deadly diseases like cancer and Parkinson’s are being backed to continue their vital work for a further five years, Science and Technology Secretary Peter Kyle will announce today (Thursday 5 September).

Currently, the 200-strong scientific community of staff and students based at the University of Dundee are using cutting-edge technology and biochemistry to explore how signals transmitted within the body’s cells are disrupted.

Their work has already delivered a drug that is now widely used to treat skin cancer, one of over 40 such drugs that are now helping patients with a range of conditions – leading to almost £60 million in investment.

Now, the MRC Protein Phosphorylation and Ubiquitylation Unit (PPU), based in the School of Life Sciences at Dundee, will receive nearly £30 million to bolster its cell biology research centre as it continues its vital work over the next five years.

Improving our understanding of these processes could be the key to unlocking the scientific basis of innovative treatments for a range of diseases - from Alzheimer’s and Parkinson’s to Crohn’s and Coeliac disease – potentially improving the lives of millions suffering with these conditions by identifying new drug candidates that could possibly treat them.

The new funding comes ahead of the Science and Technology Secretary addressing higher education representatives at the Universities UK conference at the University of

Reading, where he will reflect on his personal experience in higher education and give his full-throated backing to the sector.

He will also outline his vision for DSIT, and the crucial role universities can play in this, harnessing discoveries and innovations for novel therapies and technologies for the benefit of everyone – like those developed in Dundee.

Science and Technology Secretary Peter Kyle said:

“I went to university later in life than most, but when I did it changed everything for me. It was the first time in my life that people saw potential in me that I never knew I had and gave me the support and focus I needed to build something from it. The value of our universities, to the economy and to the whole of society, cannot be understated.

“As we embark on a decade of national renewal, the higher education sector has a profound role to play in every piece of work we’ll need to do, to build a Britain that delivers for working people: from seizing the potential of clean energy to rebuilding the NHS. I will always champion our universities. They are society’s most powerful engines for innovation, aspiration, and the creation of better lives for all – which is why investing in their work, like this £30m in funding, is so important.”

Science Minister Lord Vallance said:

“The work at the University of Dundee, which we are announcing support for today, is proof of how deep expertise, quality links with industry, and the power of genuine curiosity can deliver meaningful improvements to ordinary people’s lives.

“This funding puts the unit on track to strive for more health breakthroughs, that could help more patients live longer and healthier lives.”

Through industry collaboration, Dundee’s unit has been a fundamental part of the development and clinical approval of over 40 drugs that are now widely used to treat patients, attracting almost £60 million in investment and helping us grow our economy.

Working with other companies, including GlaxoSmithKline, the team was central to developing a drug now widely used to treat melanoma, and a promising new drug for Parkinson’s disease is in clinical trials as a result of the team’s globally recognised work, investigating the condition to discover potential causes and treatments.

Professor Dario Alessi, Director of the MRC-PPU said:

“We are incredibly grateful for the long-term support that our unit has received from the MRC over the last 34 years. This has enabled our researchers to tackle the most important questions and greatly contributed to our understanding of how derailment of

biological pathways causes human diseases including neurodegeneration, diabetes, cancer, and immune dysfunction.

“Our mission for the next five years will be to work with leading research centres, clinicians, and pharmaceutical companies to translate our discoveries into clinical progress and accelerate drug discovery. Whilst doing this research we aim to provide our staff with a unique training opportunity, working in a collaborative multidisciplinary environment and paying attention to improving culture and development best practices.”

Professor Patrick Chinnery, Executive Chair of the Medical Research Council (MRC), said:

“The MRC are proud to be investing for a further five years in the exceptional research of the MRC-PPU in Dundee. They are leaders in conducting rigorous fundamental research and then working with industry to translate those breakthroughs for patient benefit.

“The MRC-PPU have an outstanding culture of collaboration and sharing their leading research expertise, products and techniques with the wider scientific community.”

Examples of new MRC funding for research group leaders:

Decades of outstanding research lead to ongoing trial of new Parkinson’s drug
A new drug which hopes to treat Parkinson’s disease is currently in clinical trials thanks to many years of painstaking research at the MRC-PPU into a signalling protein called leucine rich repeat kinase 2 (LRRK2). The team of Parkinson’s researchers, led by Professor Alessi, focussed on the role of LRRK2 because it is the most frequent cause of inherited Parkinson's disease.

Parkinson’s disease is a progressive neurodegenerative disorder affecting more than 10 million people worldwide and currently no cure is available. Now, based on their research, a clinical trial, called the ‘LUMA trial’, is testing if a drug that inhibits LRRK2, developed by the companies Denali Therapeutics and Biogen, can slow the progression of Parkinson’s disease.

Dr Esther Sammler, consultant neurologist in charge of the LUMA trial in Dundee and newly funded MRC investigator at the MRC-PPU, said: “This is a significant step forward in the quest to develop new Parkinson’s treatments and welcoming the first UK patient into this drug trial is testament to the years of hard work undertaken here in Dundee,”

Esther leads a team in the MRC-PPU to identify biomarkers for LRRK2 and lysosomal dysfunction in Parkinson’s disease and has a joint appointment with the University of Dundee’s School of Medicine. Dr Sammler added: “There is still a lot of work ahead of us to establish whether LRRK2 therapeutics will benefit patients. The need to develop new treatments for Parkinson’s remains urgent.”

Research into debilitating conditions like inflammatory bowel diseases
Dr Mahima Swamy is newly funded by the MRC as a group leader as part of the funding announced today. She leads a team studying potential treatment targets for immune-mediated bowel diseases, including debilitating gut conditions such as Crohn’s disease and the gluten-induced autoimmune Coeliac disease.

These are serious illnesses where the body’s own immune system mistakenly attacks the tissues of the gut, which can cause it to become inflamed and ulcerated, resulting in gastrointestinal symptoms. Severe cases of Crohn’s can result in people needing surgery to have the affected part of their gut removed.

Dr Swamy’s research is investigating how the immune system functions in the gut and how cell signalling going awry can cause it to start attacking the body.

Dr Swamy said, “The funding from the MRC will help us to delve deep into the molecular bases of gut diseases. We are excited to get new insights and potential new therapeutic targets for both Crohn’s and coeliac, both chronic autoimmune diseases, that can cause long-term damage.”

The ‘world’s longest running collaboration between academic labs and industry’ 
The MRC-PPU leads a unique collaboration, called the Division of Signal Transduction Therapy, currently with two of the world’s leading pharmaceutical companies: Boehringer Ingelheim and Merck Serono.

Established in 1998, this long-standing collaboration has attracted almost £60 million of investment and has led to the development and clinical approval of over 40 drugs that target kinases, mainly for the treatment of cancers, with sales of many billions of pounds a year. For example, DSTT researchers played a significant role in aiding GlaxoSmithKline develop an anti-cancer drug, Dabrafenib (Tafinlar), targeting melanoma.

The collaboration aims to develop improved treatments for many diseases, including cancer, arthritis, lupus, hypertension and Parkinson’s disease by accelerating the early stage development of future drugs.

The pharmaceutical companies provide funding for research and benefit from close interaction with the scientific groups and other partner companies, and the advice, opinions and foresight of leading scientists.

Dr Paul Davies, Deputy Head of the MRC-PPU, said, “We believe this is the world’s longest running collaboration between academic labs and industry and it has delivered many new therapies for patients. By working with industry partners we can translate government funded research from the lab to the clinic in a faster and more effective way.”

The consortium was recognised by the Department of Trade and Industry as a model of best practice in technology transfer and has injected well over £23 million directly into the local economy.

What is protein phosphorylation and ubiquitylation?
Cells inside the body need to be able to send signals to switch processes on and off. Proteins are the work horses inside cells and one of the most common ways that their functions are switched on and off are by attaching and removing chemical tags.

Phosphorylation is the term for when a tiny molecule, called phosphate, is attached to surface of a protein. This can alter the structure of the protein, resulting in changes in its function, such as it being switched on or off. The enzyme that makes the attachment happen is called a kinase, and therefore many drugs target these enzymes.

Ubiquitylation is a similar process for altering protein function, but in this case a tiny protein called ubiquitin is attached to the larger protein.

These processes are so universal that almost all aspects of biology are regulated by reversible protein phosphorylation and ubiquitylation.

Therefore, abnormalities in these pathways are implicated in a vast array of diseases, including cancer, neurodegeneration and inflammation. However, there are thousands of different types of these proteins, so the systems are very complex and many are currently not well understood. Deciphering how disruptions in phosphorylation and ubiquitylation signals lead to disease will reveal new drug targets and improved strategies to treat many diseases.