Spotlight on science
Reproduced from Issue 136 of Arthritis Today
Professor Charlie Archer and Dr Lucy Wedderburn explain their work in an ongoing series of questions and answers with arc-funded researchers.
About Charlie
I am married with three children, two sons, aged 13 and 14, and a ten-year old daughter. Most of my spare time is taken up with DIY chores in the house (it was a bit dilapidated when we bought it) and in winter my Sunday mornings/afternoons are taken up as team ‘manager’ to the Aberdare under-15 side in which my elder son plays.
Professor Charlie Archer
What does your work involve?
My laboratory has a variety of interests. Mainly we are interested in the development of the skeleton and in particular the mechanisms of how joints form. However, over the last few years, we have been trying to apply the knowledge gained from our basic laboratory studies to clinical conditions. Specifically, we are interested in the biological repair of damaged joints and have identified specific stem cells that we think will prove very useful in clinical application.
How long has arc been funding you?
About 18 years.
What’s the most important thing you have found out in the past 12 months? And why?
We have found the existence of cells within adult and aged human articular cartilage that have the properties of stem cells. This discovery can lead to new ways of treating osteoarthritic lesions in large joints such as the knee. One technique used for healing defects in cartilage is to take some cartilage from the edge of the joint, take out the cells and grow them in tissue culture and then implant them back into the defect where they will make new cartilage. However, a major problem is that one can only grow the harvested cells for so long before they lose the ability to form cartilage when implanted back into the joint. This doesn’t happen with the stem cells and they can be grown to produce tens of millions of cells and still make cartilage thus facilitating the repair of much larger defects.
What do you hope or expect to achieve as a result of your arc funding?
Our aim is to develop cartilage stem/progenitor cells for clinical use as indicated above. However, there are a number of regulatory laws being devised both in Europe and the USA that will ensure that cells implanted into patients have very stringent quality control measures to provide maximum protection for the patient which is quite right. So, developing these new techniques will be a long-term project.
What do you do in a typical day?
My working day is seldom hum-drum as no matter how carefully you plan your day it is invariably highjacked by some issue or event that needs dealing with immediately. However, my job is increasingly bureaucratic as successive regulations either generated within the EU, UK or university come into operation. Unfortunately, this leaves less time for the exciting things such as science which after all, is what we are paid to do!!
What is your greatest research achievement?
The discovery of stem/progenitor cells in articular cartilage. That said, we have spent a lot of time studying the mechanisms of how joints form in the embryo and during post-natal development and when we started this research 23 years ago very little was known, but today we can say we understand a good deal and the discovery of the stem/progenitor cells was underpinned by these studies.
Why did you choose to do this work?
Ever since I was in the sixth form, I’ve always wanted to be a biological scientist. After graduating in zoology, I was going to pursue a career in marine zoology but realised that job opportunities were very limited. Even now, I remain interested and have recently published a book chapter on the evolution of joints which included a lot about fish!
Do you ever think about how your work can help people with arthritis?
Of course, and as is apparent from the above we are in the process of translating our scientific discoveries towards the treatment of patients which I hope if it works will be tremendously satisfying. But even science of the most fundamental nature is important and one never knows when such data can become clinically relevant.
What would you do if you weren’t a scientist?
A chef but not of the celebrity variety!
- Charlie Archer is Professor of Reparative Biology and Tissue Engineering in the Connective Tissue and Biology Laboratories at Cardiff University.
About Lucy
Outdoors, my passion is cycling- which can take me to fantastic places, the most recent being the southern hills of Spain. My partner and I are planning a trip to the Derbyshire hills next, and the goal after that is to ride the coast to coast (W to E is less windy…). Indoors, music is a major love and route to relaxation; I still do some choral singing, but one day will do more. I spend as much time as I can with my two godsons and their families.
Dr Lucy Wedderburn
What does your work involve?
The work of my group is to find out why arthritis and related conditions in children happen, with a focus on parts of the immune system which are abnormal in these diseases. The childhood immune system differs from that of adults. For example in children there is more chance of successfully switching off inflammation and restoring what immunologists call ‘tolerance’. Once we understand tolerance fully, we should be able to design ways to switch off inflammation, like arthritis. Much of the work of my group involves the study of cells and tissues from patients: we focus mainly on juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) a condition which affects muscles. We also use model systems when needed as these can allow us to test our theories more directly.
How long has arc been funding you?
Since 2003. We had a fellowship award to work on our model system of JDM. This has been very exciting and led to new findings – we have evidence that in children muscle is more able to restore muscle function after damage, than in adults. More recently we have been awarded a project grant to look at the immunological factors which control whether JIA stays mild, or becomes more severe.
What’s the most important thing you have found out in the past 12 months? And why?
One important thing is that we have shown that in mild arthritis in children the immune system manages to generate a more powerful ‘regulating’ response to arthritis, as measured by the number of a type of cell, called regulatory T cells, in the joint. This led us to the next stage - asking whether measuring these cells can predict mild arthritis. The other important finding is that we have shown that alteration of just one molecule, MHC Class l, in young muscles leads to more severe disease, like that seen in our JDM patients, than in adults. This means we can now explore differences between adults and children using the information from this model system.
What do you hope or expect to achieve as a result of your arc funding?
We hope that our work on childhood arthritis and myositis will provide explanations of why these diseases persist, which parts of the immune system are altered in these children, and then allow us to design ways to stop these diseases from damaging the joints and muscles. We also hope this work will lead to information to apply beyond these specific conditions, to help understand the related conditions in adults.
What do you do in a typical day?
The great thing about research is that it is so varied, so there is no truly ‘typical’ day. The best days are those when administrative paperwork is not allowed to obscure time for science, and we get some exciting new data in the lab. I do one clinical day a week, seeing children with arthritis and related conditions; I also do various teaching seminars throughout the year.
What is your greatest research achievement?
Perhaps the most important finding is that we showed that the attempt of the childhood immune system in JIA to control arthritis is directly correlated with the type of arthritis. I hope that this ‘puts T cells on the map’ in paediatric rheumatology. More broadly I think that my achievements in the past few years have been to build and recruit a group of young talented researchers who are inspiring to work with, to take our work forward in the next few years.
Why did you choose to do this work?
It is fun, interesting, challenging and always has new things to think about. Above all I love the variety. The work takes me into new fields and ways of working and allows me to think about the patients I see in ways that drive the work in the lab, and vice versa.
Do you ever think about how your work can help people with arthritis?
Yes, a lot of time is spent thinking about this. Many of our projects are aimed at finding ways to predict how arthritis in children will develop, how children will respond to treatment, how to predict these differences and how to intervene more appropriately before there is damage to joints and muscles.
What would you do if you weren’t a clinician/scientist?
Re-learn to play the violin well, see more of my family and friends, and tour the world on eco-friendly (slow) forms of transport, maybe writing a book illustrating the worlds metro systems (amazingly varied), along the way.
- Dr Lucy Wedderburn is a reader and honorary consultant in paediatric rheumatology at the Institute of Child Health, University College, London.
