Spotlight on science
Reproduced from Issue 139 of Arthritis Today
Dr Michelle Fernando and Dr Alison McGregor explain their work in an ongoing series of questions and answers with arc-funded researchers.
About Michelle
I’ll let you know in June when I have some spare time!
Dr Michelle Fernando
What does your work involve?
My research involves finding genes that cause lupus. The cause of lupus is not known, but we do know that genes play a significant role in predisposition to this disease. Therefore studying the genetic material or DNA (which contains our genes) of people who have lupus is essential in discovering and understanding what causes lupus. By studying lupus DNA, I (along with other researchers in this field) also hope to identify genes that could be the target for future treatments in lupus and other autoimmune diseases. I undertook my three year PhD in Professor Tim Vyse’s laboratory at the Hammersmith Hospital campus of Imperial College London. Professor Vyse has the largest collection of lupus DNA samples in the United Kingdom and collaborates with other lupus researchers in the UK, Europe, America and Canada. I am particularly interested in a group of genes on chromosome 6 many of which are involved in the regulation of the immune system. Studies have shown strong association with lupus and this region on chromosome 6 called the major histocompatibility complex (MHC). We know that this region contains the genes with the strongest effect on lupus susceptibility. However the identity of the actual gene(s) within the MHC that cause lupus has remained elusive. With new advances in technology, I hope to make real headway in the hunt for these disease-causing genes.
How long has arc been funding you?
arc funded my PhD in the form of a clinical research fellowship from 2004 to 2007. I am currently finishing my training as a rheumatologist at a busy district general hospital in London whilst trying to publish my research findings to date and finalising my PhD thesis. I was recently successful in obtaining a clinician scientist fellowship from arc which will begin in June in Professor Vyse’s lab. This funding will enable me to continue research in the field of lupus genetics.
What’s the most important thing you have found out in the past 12 months? And why?
The most important thing that we have discovered in the last 12 months is that there are at least two separate groups of genes within the MHC that are involved in lupus in UK families. This is the first time that this has been shown and is an important step in identifying what the actual genes are. One group of genes affects the way the body’s immune system may target its own tissues. We are currently studying how the second set of genes predisposes to lupus.
What do you hope or expect to achieve as a result of your arc funding?
I hope to contribute to the understanding of the disease process that underlies predisposition to lupus and other autoimmune diseases. By doing so I hope to identify markers/molecules that will be helpful in assessing the severity of disease in lupus sufferers and therefore be of help in guiding patients’ treatment more successfully than is presently available. I also hope to identify molecules involved in lupus that could act as targets for better drug treatment in the future.
What do you do in a typical day?
Every day is extremely variable, unpredictable and busy – which is just as well as I get bored easily. Any given day involves a combination of looking after patients with rheumatological and general medical problems in outpatient clinics as well as on the wards. I could also be on-call in A and E (I won’t miss that when my six months is completed), teach medical students and junior doctors, attend teaching sessions myself and finalise manuscripts, my thesis and participate in conference calls with collaborators in America and Canada as part of my ongoing research.
What is your greatest research achievement?
As my research career is in its infancy, my greatest research achievement is yet to come. In my PhD work, the most important finding was disentangling the complex genetics of the MHC and lupus and showing that at least two separate genes are involved in the development of lupus from the MHC region.
Why did you choose to do this work?
The fact that lupus can affect any organ in the body and that each patient will have a different constellation of problems caught my attention and interest when I was a medical student.
Do you ever think about how your work can help people with arthritis?
Looking after patients with lupus is challenging and rewarding and with recent advances in technology coupled with the pooling of patient samples through collaborations with scientists all over the world I feel that we are now in a position to make great advances in identifying the different genes, molecules and pathways that contribute to lupus susceptibility. By doing so this research should be able to help people with lupus and also people with other types of arthritis, as we do know that some gene variants are common to different forms of arthritis.
What would you do if you weren’t a clinician/scientist?
I would be a translator for the United Nations.
- Michelle Fernando is an arc clinical research fellow at Imperial College London
About Alison
I am married to one of the GB international rowing coaches so rowing and sport plays a large part in our lives. We both run and train regularly and have been known to do the odd half marathon. I am also the DIY demon in the house when my husband is away on training camps!
Dr Alison McGregor
What does your work involve?
I am part of the Human Performance Group within the Department of Biosurgery & Surgical Technology at Imperial College London. One of the group’s main research areas is the spine and its related diseases including low back pain and sciatica. Our research extends from the normal population to those with back problems and elite athletes, which is a huge spectrum and means lots of variety. We are interested in how the spine functions in terms of how it moves during different daily tasks, how the muscles work and how the brain controls these muscles, not to mention how things like back pain and sciatica impact on this. We are now starting to use some of this information to direct management and hope that in the future this knowledge of what goes wrong will contribute more to a greater understanding of how back pain should be managed.
How long has arc been funding you?
arc has been funding research into our group for the past five years, initially with a project grant investigating the wiring of the brain to the back muscles. Currently, arc has funded a large clinical study: Function after spinal treatment, exercise and rehabilitation (FASTER), which aims at determining the optimal post-operative management for people having spinal surgery.
What’s the most important thing you have found out in the past 12 months? And why?
A tough question as so many projects are in their formative stages. We have been establishing an MRI technique that may help us determine the structure of muscle in terms of fat and fibre content both of which we know are altered as a result of back pain. The hope is that we can use this to investigate how to change this structure, so watch this space!
What do you hope or expect to achieve as a result of your arc funding?
The aim of our clinical trial is to find out what is the best way to manage people after spinal surgery so we can maximise their recovery and return to everyday daily tasks. Currently there is a lot of uncertainty and patients get limited and often conflicting advice on what they should and shouldn’t do. We hope to change this for both them and their consultants.
What do you do in a typical day?
There is so much variety from overseeing the FASTER study and helping with recruitment, to supervising other research projects, getting new ideas off the ground, not to mention other academic commitments like teaching and administration. The most consistent thing in my day is the need for a strong coffee mid-morning!
What is your greatest research achievement?
I am hoping that completing the FASTER will be one of my greatest achievements. There have been lots of complications and problems on the way with surgeons leaving, centres dropping out, and hospitals closing that have made it a real challenge. It has also taught me an awful lot about clinical trials and running them, the pitfalls and challenges. Hopefully the results will be rewarding and may lead to a chance in clinical practice if our hypothesis is right!
Why did you choose to do this work?
I am fascinated by how the body works and moves and how this can go wrong through either injury or disease and believe that an understanding of this can be used to manage patients more effectively and make their lives better. I think the constant challenge of research and how we always end up asking more questions than we answer keeps me motivated and interested in research. I don’t think all jobs offer this kind of challenge.
Do you ever think about how your work can help people with arthritis?
Of course, so much of what we do in our laboratories has the potential to help people with arthritis, although sometimes it must seem for them, as well as us, a long journey. FASTER is a good example; it started from a project we did almost ten years ago which looked at how people did after spine surgery. Many patients were disappointed with their improvements after surgery and few saw a change in what they could do on a day to day basis. Of top of this many patients taking part complained about the lack of post-operative care support they had which made them very unsure about what they should and shouldn’t be doing. This was borne out by our survey of usual practice by surgeons, and led to the development of a patient evidence-based information booklet, a rehabilitation programme and of course the clinical trial which has now been running for two and a half years.
What would you do if you weren’t a researcher?
I once thought professional sport would be great, but having worked closely with athletes I realise that not only do I not have the physiology but I don’t have the drive to push myself physically to the limits. However, having done a parabolic flight as part of our research I’d love to be an astronaut; weightlessness was quite spectacular!
- Dr Alison McGregor is a reader in biodynamics at Imperial College, London.
