Nature paper, child, Nature paper, child, Nature paper… Carola Vinuesa has had a busy few years. Her research has revealed key steps in how our immune system produces high quality, long lasting antibodies to fight disease.
And she has discovered what happens when things go wrong: that a single letter change in the genetic code is enough to create poor quality antibodies and trigger autoimmune diseases like lupus, juvenile diabetes and certain cancers.
This 39-year-old researcher’s work at the John Curtin School of Medical Research at the Australian National University is opening up new targets for drug discovery to fight autoimmune disease.
For her contributions to immunology, Carola Vinuesa receives the 2008 Science Minister’s Prize for Life Scientist of the Year.
As a young Spanish volunteer medic working in Africa and India, Carola saw first hand the impact of infectious diseases that still kill millions of people.
She returned to Europe to complete her medical training. But the protocol-driven world of clinical care wasn’t for her.
“I realised that I could save more lives researching diseases than treating them,” she says. An immunology lecturer inspired her to tackle the complexities of the human immune system.
“We lead much healthier and longer lives today than 50 years ago due to a dramatic improvement in health care and overall wealth,” she says. “That is why it is hard to understand why the incidence of autoimmune diseases keeps steadily increasing, affecting around one in eight Australians.”
“Despite intensive research, no cure has yet been found, and treatments still rely on drugs that dampen the whole immune system and can cause serious long-term side effects.”
The starting point for Carola’s seminal discoveries was when she was awarded an international postdoctoral fellowship to work at the John Curtin School of Medical Research with Chris Goodnow.
Working with mice affected by random mutations, she found some had signs of lupus. The mice were making antibodies that were attacking their own tissues.
To determine why these mice were producing rogue antibodies, she and her colleagues worked backwards to discover that a single point mutation in a single gene was causing the condition. She named the gene roquin (pronounced rockin) after the patron saint of plague victims.
“The next question was obvious,” says Carola. “What does the healthy roquin gene do?”
It took two years to find the answer.
“We found that roquin plays a critical role in the quality control of antibodies. It stops the production of poor quality or ‘rogue’ antibodies that would attack ‘self’.”
And the way it does this is intriguing. When our immune system detects an invading pathogen, immune cells known as B-cells start producing antibodies. Special helper T-cells assist, but if they are damaged then bad antibodies can result. Carola discovered that roquin helps stop these damaged T-cells.
In essence, roquin turns out to be a central player in regulating the quality of antibodies. But that’s not all.
“We also found that roquin works hand-in-hand with what until recently was called ‘junk DNA’. The DNA makes small RNA molecules that, with the help of roquin, control the production of a protein called ICOS that is needed by the helper T-cells.”
It’s complex science, and there’s still much to do. But the discovery of the roles of ICOS and micro-RNA molecules opens up opportunities for developing new drugs.
“It may one day be possible to use antibodies or micro-RNA molecules to treat autoimmune disease,” says Carola.
2000 Doctor of Philosophy in immunology, University of Birmingham, UK
1997 Master of Science in immunology, University of Birmingham, UK
1995 Diploma of the Royal College of Obstetricians & Gynaecologists, UK
1993 Licentiate in Medicine and Surgery/Bachelor of Medicine, Bachelor of Surgery, University Autonoma of Madrid, Spain
2007-present Viertel Senior Medical Research Fellow, John Curtin School of Medical Research, Australian National University
2006 Senior Research Fellow/Group Leader, John Curtin School of Medical Research, Australian National University
2001-2005 Wellcome Trust Research Fellow, John Curtin School of Medical Research, Australian National University
1997-2000 Medical Research Council Clinical Research Fellow, University of Birmingham Medical School, UK
1996-1996 Senior House Officer HIV & Genitourinary Medicine, Whittall Street Clinic and Selly Oak Hospital, Birmingham, UK
1994-1996 Senior House Officer-Vocational Training Scheme, Geriatric Medicine; Obstetrics and Gynaecology, Paediatrics Hereford Hospitals, UK
1993-1994 Junior House Officer, Wirral Hospitals, UK General Surgery; General Medicine
1991 Village Concept Project, Ojobi, Ghana; International Federation of Medical Students’ Associations/Department of Community Health, University of Ghana Medical School
1990 Nimtollah Bathing Ghat Clinic, Calcutta, India. Volunteer work with Calcutta Rescue NGO; Medical and surgical assistance to leprosy and tuberculosis patients
Awards and fellowships
2007 Biogen-Idec III prize, Spain
2007 Young Tall Poppy Science Award NSW & ACT
2007 Sylvia and Charles Viertel Senior Medical Research Fellowship
2001 Wellcome Trust International Prize Travelling Research Fellowship, UK.
1997 Medical Research Council Clinical Training Fellowship, UK
1997 Prize for best academic performance (MSc with Distinction), University of Birmingham, UK
- Vinuesa, C.G., Cook, M.C., Angelucci, C., Athanasopoulos, V., Rui, L., Hill, K.M., Yu, D., Domaschenz, H., Whittle, B., Lambe, T., Roberts, I.S., Copley, I.R., Bell, J.I., Cornall, R.J., and Goodnow, C.C. A novel RING-type ubiquitin ligase family member essential to repress follicular helper T cells and autoimmunity. Nature 435, 452-458, 2005.
- Vinuesa, C.G., Tangye S G, Moser B and Mackay C R: (2005) Follicular B helper T cells in antibody responses and autoimmunity. Nature Rev. Immunol. Nov 5(11), 853-65, 2005.
- Goodnow, CC., Sprent, J., Fazekas de St Groth, B., & Vinuesa, C.G. Cellular and genetic mechanisms of self-tolerance and autoimmunity. Nature 435, 7042, 2005.
- D. Yu, A. H-M. Tan, X. Hu, V. Athanasopoulos, Simpson, K. M., D. Silva, A. Hutloff, Giles, P.J. Leedman, K.P. Lam, N., C.C. Goodnow and C.G. Vinuesa. Roquin represses autoimmunity by limiting inducible T cell costimulator messenger RNA. Nature 450, 299-303, 2007.
- M. Liu, J.L. Duke, D.J. Richter, C.G. Vinuesa, C.C. Goodnow, S.H. Kleinstein and D.G. Schatz. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451, 841-845, 2008.