Researcher Spotlight: Professor Sir Philip Cohen

Sir Philip Cohen is a professor of enzymology at the University of Dundee. He holds a Wellcome Trust Senior Investigator Award and has worked in the field of protein phosphorylation and cell regulation for over four decades. His work on the subject has seen him consistently ranked as one of the world’s most cited scientists in the field of biology and biochemistry. Prof Cohen was recently presented with the Albert Einstein World Award of Science from the World Cultural Council. We asked him to share some of the highlights of his career, and what got him interested in this area of research…

What are you working on?

I am trying to understand in molecular detail how the innate immune system is regulated. This system is vital for defence against microbial pathogens but its deregulation causes many chronic inflammatory and autoimmune diseases that include arthritis, asthma, colitis, fibrosis, lupus, psoriasis and sepsis.

What does your average day involve?

I was the Director of Research in the College of Life Sciences at Dundee from 1984-2006 and Director of the Medical Research Council Protein Phosphorylation Unit from 1990-2012, so for nearly 30 years I had huge administrative responsibilities in addition to running my own research team. However, having shed all my administrative responsibilities over the past few years, I am now in the wonderful position of being able to devote virtually all of my day to my own research interests. I therefore spend much of my day planning and discussing the work of my research team, reading the scientific literature to help formulate new ideas for my research, writing research papers and occasionally reviews.

Why is your work important?

Understanding how the innate immune system works is critical to identify which protein components of this signalling network may be the most attractive drug targets for the treatment of inflammatory and autoimmune diseases. For the past 18 years I have been running the Division of Signal Transduction Therapy, which is Europe’s largest collaboration between an academic research centre and the pharmaceutical industry. Through this collaboration, I am able to pass on the important information I come up with rapidly to six of the world’s largest pharmaceutical companies, which has helped to launch and accelerate many new drug discovery programmes.

How did you come to be working on this topic/in this field?

For the past 45 years I have been studying the function of reversible protein phosphorylation (i.e. the attachment and removal of phosphate from proteins) in cell regulation and human disease. When I started working on this topic it was thought to be a specialised control mechanism confined to the regulation of glycogen metabolism, but as a result of work in my lab and many others, it gradually became clear that it regulates almost all aspects of cell life and that abnormalities in this process cause many diseases.

In the 1970s, 1980s and 1990s I was involved in working out how insulin stimulates the conversion of glucose to its storage form glycogen, in identifying and characterising the enzymes that remove phosphate from proteins (called protein phosphatases) and in identifying many of the enzymes that attach phosphate to proteins (called protein kinases) and how they were activated in response to growth factors and cell damaging agents. However, eventually the outlines of these systems became clear and I started to look for other important systems to which the expertise and technologies that I had developed could be applied to and eventually stumbled across the innate immune system and became fascinated by it.

Immunologists had made seminal advances in identifying some of the key components of these systems, but it was obvious to me that our knowledge of the wiring diagram that controls this complex process was still in its infancy and that there was a chance to make a significant impact and rewrite the textbook accounts of what was going on. So about seven years ago I took the plunge and switched all of my research effort to try and crack this problem. It is one of the best decisions I have ever made.

Changing my research to innate immunity introduced me to another general biological control mechanism called “reversible ubiquitylation” and I have become increasingly fascinated by how the two control mechanisms of protein phosphorylation and protein ubiquitylation “talk” to each other. I managed to persuade the Scottish National Party to give me £10 million six years ago to set up a new Protein Ubiquitylation Unit at Dundee, which was absorbed into the MRC Protein Phosphorylation Unit last year and was renamed the MRC Protein Phosphorylation and Ubiquitylation Unit.

How has Wellcome funding helped you/your research/your career?

You may be amused to know that from 1975-1978 I was the recipient of a “Wellcome Trust Special Fellowship”, which I believe was the first ever Career Development Fellowship awarded by the Wellcome Trust. This Fellowship freed me from all undergraduate teaching commitments and was hugely beneficial for my research career.

Subsequently, my salary was paid by the MRC for five years and then for 16 years by the Royal Society (I was a Royal Society Research Professor from 1984-2010). So when I was awarded a Senior Investigator Award in 2013 it was the first research grant I had been given by the Wellcome Trust for 35 years! However, the Wellcome Trust had been a huge help to me in developing the Life Sciences at the University of Dundee. The £10 million that the Trust awarded me in 1994 to set up the Wellcome Trust Biocentre at Dundee, which opened in 1997, was a transformational event in bringing research in the life sciences to a new level in Dundee.

What’s the most frequently asked question about your work?

To describe my research in laymen’s terms and say why it is worth doing.

Which question about your work do you most dread – and why?

I am always happy to field any question about my research. However, I only started work in the field of immunology seven years ago and still regard myself as a beginner in the field. I am still learning something new about this topic every day, which is one of the joys of changing one’s research field.

I am always expecting to be caught out by a really difficult immunological question, but I don’t dread it, I just consider it to be part of my new learning experience. 

Tell us something about you that might surprise us…

I was a well-known boy soprano in the 1950s appearing on the British and German radio on many occasions. I ran the London University Chess team at University and played in many East European Countries and Russia in the mid 1960s and continued to play chess competitively for the City of Dundee into the 1980s.

I studied Biochemistry at University because I was (and still am) passionate about Natural History and quite good at Chemistry, so Biochemistry seemed the natural combination of these interests. Much of my spare time is spent bird watching and (in the season) picking wild mushrooms. My house is on the Estuary of the River Tay and I have seen nearly 120 bird species through the telescope trained from my bedroom window. I have played golf in Pro-Am tournaments with many of the world’s most famous golfers including Gary Player, Sir Bob Charles, Fred Couples and Craig Stadler.

What keeps you awake at night?

Nothing – I sleep like a log, but get up very early

What’s the best piece of advice you’ve been given?

After two year’s postdoctoral research at the University of Washington, Seattle, I made a visit to the UK in 1971 to decide which job to accept. On arrival I thought that I would probably accept a Fellowship at the MRC Laboratory for Molecular Biology (LMB) at Cambridge. It was Brian Hartley at LMB who advised me not to do this and told me that if I had an interesting research problem that I wanted to tackle I should take a permanent lectureship at a University right away and get on with it.

When I mentioned the three lectureship offers that I had received, Brian said that he thought that Dundee might become interesting since Peter Garland had just moved there from Bristol to become its first Professor of Biochemistry. I hit it off with Peter and the rest is history. So without Brian’s great advice my career might have been very different.

To find out more about Prof Cohen’s work, you might like to read his article for the Reflections series in the Journal of Biological Chemistry from 2009, called Keep nibbling at the edges. He has published over 530 scientific papers, but two of his more recent ones are Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains and Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages.

Image credits: University of Dundee