Spotlight on science
Reproduced from Issue141 of Arthritis Today
Dr Frances Williams and Dr Alex Betz explain their work in an ongoing series of questions and answers with arc-funded researchers.
Dr Frances Williams
About Frances
I am married with three young children so my activities tend to fit around them. I like music and go to concerts and opera. I also enjoy jogging, fishing and skiing.
What does your work involve?
I am trying to understand the common problem of back pain by approaching it through the genetics of degenerative disc disease (DDD). DDD is a very common, age-related condition which has a strong influence on back pain. Back pain, as highlighted in issue of Arthritis Today 138, is a major cause of disability in those of working age and it is increasing in prevalence in Western countries. We are studying healthy volunteer twins who underwent spine MRI scanning as part of previous studies some 10 or so years ago. The previous study showed that DDD is highly heritable so now the search for the genetic factors involved is taking shape. In addition, we are rescanning this same group of twin volunteers to look at the biology of progression of DDD and to see if this relates to the length of telomeres, structures at the ends of chromosomes.
How long has arc been funding you?
This arc-funded project has been funded for approximately 18 months, but the work builds extensively on previous studies which were also, in part, arc-funded.
What’s the most important thing you have found out in the past 12 months? And why?
I have learnt a lot about the administration of a large and complicated clinical project. Twins come to visit us at St Thomas’ from all round the UK and, in a packed and complicated day of tests, they travel round London to various sites for scans, x-rays and blood tests. We have fantastic people working at the Twin Research Unit and I rely heavily on various teams to pull together and arrange these timetables. On the research front, we have just identified a novel genetic variant which appears to be associated with DDD, back pain and bone mineral density. I cannot name it until we have done more work on it – but it is a very exciting find!
What do you hope or expect to achieve as a result of your arc funding?
The ultimate aim is to identify changes in the DNA code which predispose to DDD. The pathological processes involved in DDD are poorly understood. By coming at the problem from a genetic angle, I hope to identify the important genes and hence the cellular pathways involved. This could lead to the development of new drugs and prognostic tests based on the knowledge of the cellular pathways.
What do you do in a typical day?
It is a cliché but there is no typical day! Yesterday, for example, I held the monthly rheumatology clinic for musicians at St Thomas' which is very enjoyable because I meet such interesting people. (This is a specialist clinic specifically for the musculoskeletal problems of musicians – any musician can attend if their GP refers them). I attended journal club in the Twin Unit at which the researchers discuss a recent research paper of interest and consider how it might inform our work. Then I worked on the spine MRI scans and x-rays we have collected from the twins. They need coding for degenerative change. This is difficult work, and I am not used to squinting at films for hours, and it gives me backache!
What is your greatest research achievement?
If the novel genetic variant we have identified in DDD turns out to be a real finding, it will undoubtedly be my greatest contribution so far.
Why did you choose to do this work?
Back pain is one of the most important musculoskeletal conditions but it has not had research funding to match, for example, cancer or Alzheimer’s disease. This means that our understanding of DDD is very poor and we have a lot of catching up to do. Current management involves painkillers and exercises for back and abdominal muscles. If we can make scientific findings which improve on this, then this will be time and money well spent.
Do you ever think about how your work can help people with arthritis?
I think it is important to direct efforts where improvements will help the most people – particularly if you are funded by public money. It is a major long-term goal to identify cellular pathways which could be targeted with more specific drugs than simple painkillers.
What would you do if you weren’t a clinician/scientist?
I can’t imagine. It is what I always wanted to do. I am extremely lucky to have such a varied and fascinating job.
- Dr Frances Williams is a senior research fellow at St Thomas’ Hospital in London.
Dr Alex Betz
What does your work involve?
About Alex
My family consists of my wife, three children, a dog and a pony. We also used to have a hamster, but that was before the dog… I cannot remember ever being bored – not for a minute!
As a group leader at the MRC Laboratory of Molecular Biology I am fortunate enough to be able to completely concentrate on research with relatively little teaching and administrative responsibilities. My group is trying to understand the initiation phase of immune responses. A wrong decision at this point might either result in a failure to defend the body against invading pathogens such as viruses or bacteria or, on the other end of the spectrum, in an attack of the body itself. The latter is the case in arthritis. By understanding the molecular mechanisms that are involved in this decision making process, we hope to find new therapeutic avenues.
How long has arc been funding you?
Since 2005, arc has been funding two projects in my lab. The aim of the first project is to understand why many women experience an improvement in the symptoms of arthritis during pregnancy. The second one has just started and aims at developing a novel therapeutic approach to treat arthritis and other autoimmune diseases.
What’s the most important thing you have found out in the past 12 months? And why?
We have developed a strategy that promises to allow us to stop immune responses on demand. We were able to show that our approach works in mice. Whilst we feel that there is a long way to go until this strategy can be used in human patients, we are nevertheless very excited. Our primary aim is to understand fundamental biological processes. Thus, we do not set out to cure a particular disease, but instead focus on gaining mechanistic insight. Once we understand how the decision making process of the immune system works, we can find ways to modulate it.
What do you hope or expect to achieve as a result of your arc funding?
Our current aim is to extend on our recent finding that we can use genetically modified T cells in a way that allows us to change their behaviour on demand. This allows us to use them in a ‘Trojan horse’ approach to stop undesirable immune responses. Whilst we are still working hard on refining this approach in mouse models, over the next few years we would like to examine whether our approach is transferable to human patients.
What do you do in a typical day?
The most interesting aspect of my work is that there isn’t a typical day. My work ranges from planning experiments, giving seminars, discussing results with members of my lab, reviewing grants, to the occasional bench work. Despite the fact that my administrative responsibilities are relatively small there are still loads of emails to be answered, manuscripts to be reviewed, grant applications to be written and publications to be read. In most cases, progress in research does not come from flashes of inspiration, but rather from re-examining data over and over again from different angles. I still find it most rewarding when I have the opportunity to do some experimental lab work myself.
What is your greatest research achievement?
Being able to demonstrate that regulatory T cells (a specialised immune cell type which is commonly associated with the prevention of autoimmunity) play a crucial role in the prevention of the rejection of the foetus by the maternal immune system was clearly a highlight. However, I wouldn't like to dwell too long on past achievements, as I hope the best is still to come.
Why did you choose to do this work?
I am very nosey. It bugs me if I do not understand how something works. Even as a child I constantly took things apart to find out how they work. To the frustration of my parents I was not quite as accomplished at putting them together again. This is probably the reason why they encouraged me to focus on research rather than medicine.
Do you ever think about how your work can help people with arthritis?
Of course I do, and not only out of compassion. I am very aware that our research is extremely expensive and that there are expectations attached to our funding. I feel fortunate that our research has taken us in a direction where we can see a clear path to direct benefits for patients, even if it will still take a long time to make it into the clinic.
What would you do if you weren’t a scientist?
The time I started my scientific career coincided with the advent of personal computing and the internet. I found that very exciting too, and probably would have started my own ‘web’ company if I wouldn’t have fallen in love with molecular immunology first.
- Dr Alex Betz is an immunologist and group leader at the MRC Laboratory of Molecular Biology in Cambridge.
